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Sample records for viable first-line treatment

  1. Inhaled Steroids: First Line Treatment of Adult Asthma

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    André Cartier

    1995-01-01

    Full Text Available Corticosteroids are the most potent inhaled anti-inflammatory drugs for asthma treatment. This paper reviews the clinical evidence supporting the early use of inhaled steroids in asthma as a first line treatment. Inhaled steroids can probably alter the course of asthma, especially in mild asthmatics. Once they have been shown to improve control of asthma and even if the need for beta2-agonists is virtually nil, their use should be continued at low doses (ie, equivalent to 400 to 500 μg of budesonide or beclomethasone for at least one year before attempting to reduce the dosage.

  2. Cetuximab in first line treatment of metastatic colorectal cancer

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    Carlo Barone

    2012-07-01

    Full Text Available The present health technology assessment report evaluates the clinical and economic profile of cetuximab in first-line metastatic colorectal cancer (mCRC in Italy. The first part of the report addresses the epidemiological, clinical, social and economic impact of mCRC. In the second part, evidence of efficacy, safety and cost-effectiveness of cetuximab and its available alternatives is shown. Finally, a model-based economic evaluation aimed at comparing cetuximab-based re­gimens vs. alternative therapeutic strategies indicated in mCRC in Italy is presented. The model estimates the incremental cost-effectiveness of adding cetuximab to FOLFOX-4 or FOLFIRI based on KRAS status, vs. adding bevacizumab to FOLFOX-4 or vs. FOLFOX-4 or FOLFIRI alone. A theoretical analysis vs. panitumumab has also been performed, despite panitumumab is not yet reimbursed in Italy in first-line mCRC. Survival outcomes, quality of life and costs of patient ma­nagement are estimated through a Markov model, using the Italian National Healthcare Service (NHS perspective, over a 10 year period, taking into account KRAS status of patients. The results of the pharmaco-economic analysis show that cetuximab + FOLFOX-4 and cetuximab + FOLFIRI are associated with increased survival, increased cost and increased quality adjusted survival, compared to all other treatments currently indicated and reimbursed in Italy. Adding cetuximab to FOLFOX-4 or FOLFIRI, based on KRAS status shows favorable incremental cost-effectiveness ratio (ICER vs. adding bevacizumab to FOLFIRI or vs. FOLFOX-4 or FOLFIRI alone. ICER of cetuximab (in combination with FOLFOX-4 or FOLFIRI, compared to currently reimbursed alternatives, is estimated between 6 and 13 thousand Euros per QALY gai­ned, depending on alternative treatment. These estimates are robust in extensive sensitivity analyses. As a final result, both clinical and economic evidence analyzed in this health technology assessment leads to

  3. First-line treatment of acute lymphoblastic leukemia with pegasparaginase

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    Riccardo Masetti

    2009-07-01

    Full Text Available Riccardo Masetti, Andrea PessionPediatric Oncology and Hematology Unit “Lalla Seràgnoli”, University of Bologna, Bologna, ItalyAbstract: Acute lymphoblastic leukemia (ALL accounts for almost 4000 cases annually in the United States, approximately two thirds of which are in children and adolescents. Treatment results of ALL have improved considerably in the past decade, due to an optimal stratification of patients and a rational use of different antileukemic agents among which L-asparaginase (L-ASNase plays a fundamental role. This drug has been used in pediatric ALL chemotherapy protocols for almost 3 decades. In the 1970s and 1980s a chemically modified form of this enzyme called pegasparaginase (PEG-ASNase was rationally synthesized to decrease immunogenicity of the enzyme and prolong its half-life. The different advantages of PEG-ASNase have been demonstrated in many clinical studies, the last of which underline the utility of this drug in front-line therapy of ALL. In this review, we discuss the pharmacological advantages and clinical potential of PEG-ASNase and its important use in first-line treatment of ALL.Keywords: pegasparaginase, acute, lymphoblastic leukemia, pegylation

  4. First-line treatment of metastatic melanoma: role of nivolumab

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    Force J

    2017-02-01

    Full Text Available Jeremy Force,1 April KS Salama,1,2 1Division of Hematology/Oncology, Duke University Medical Center, Durham, NC, USA; 2Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA Abstract: Historically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients. We discuss advances in immunotherapy while focusing on the use of nivolumab alone and in combination with other agents, including ipilimumab in advanced melanoma. One major goal in melanoma research is to optimize combination strategies allowing for more patients to experience benefit while minimizing toxicity. A better understanding of the optimal sequencing, combinations, and mechanisms underlying the development of resistance may provide evidence for rational clinical trial designs of novel immunotherapy strategies in melanoma and other cancer subtypes. Keywords: PD-1, immunotherapy, pembrolizumab, PD-L1, resistance, checkpoint, BRAF

  5. Retrospective analysis of first-line treatment for follicular lymphoma based on outcomes and medical economics.

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    Muneishi, Manaka; Nakamura, Ayaka; Tachibana, Katsumi; Suemitsu, Junko; Hasebe, Shinji; Takeuchi, Kazuto; Yakushijin, Yoshihiro

    2018-04-01

    Follicular lymphoma (FL) is the most common type of non-Hodgkin lymphoma (NHL), with indolent progression. Several treatment options are selected, based not only on disease status, quality of life (QOL), and age of patient, but also on recent increasing medical costs. We retrospectively analysed the first-line treatment of FL with regard to treatment outcomes and medical economics, and discuss the appropriate strategies for FL. Data on a total of 69 newly-diagnosed patients with FL was retrospectively collected from 2001 to 2015. The median age of the patients was 60 years and the median follow-up was 58 months. A total of 25 cases with FL were treated with R monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The factors affecting the decision of physicians to use R or R-CHOP treatment were serum level of lactate dehydrogenase (LDH) and disease stage. The first-line treatment-associated survival did not show any statistical differences between R and R-CHOP. The average hospitalization and average of all medical costs during the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY 1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP), respectively. R monotherapy for patients whose diseases show low tumor burden and who are not candidates for local treatment has benefits as a first-line treatment compared to R-CHOP, based on the patients' QOL and medical economics.

  6. Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy.

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    Gisbert, Javier P; Barrio, Jesús; Modolell, Inés; Molina-Infante, Javier; Aisa, Angeles Perez; Castro-Fernández, Manuel; Rodrigo, Luis; Cosme, Angel; Gisbert, Jose Luis; Fernández-Bermejo, Miguel; Marcos, Santiago; Marín, Alicia C; McNicholl, Adrián G

    2015-02-01

    Helicobacter pylori eradication is a challenge in penicillin allergy. To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.

  7. [First-line treatment of lymphomas of "high grade malignancy" or "aggressive lymphomas"].

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    Reyes, F

    2001-11-01

    Main strategies used as first line treatment of aggressive lymphoma are the subject of this review. The evolution of histopathlogical classifications is reviewed and the concept of aggressive lymphoma is given. General principles of chemotherapy treatment and main prognostic factors that direct therapeutic decisions are described. The treatment modalities of localized and advanced disease are detailed, as well as the role of high-dose therapy with hematopoietic support. Finally, the major impact of immunotherapy based on the monoclonal anti-CD20 antibody is envisaged.

  8. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors

    International Nuclear Information System (INIS)

    Roche, Alain; Girish, Baragur V.; de Baere, Thierry; Baudin, Eric; Schlumberger, Martin; Boige, Valerie; Ducreux, Michel; Elias, Dominique; Lasser, Philippe

    2003-01-01

    Our objective was to report the outcome in patients with liver metastasis from endocrine tumors who underwent transarterial chemoembolization (TACE) as first-line non-surgical treatment. From January 1990 to December 2000, 14 patients with progressive unresectable liver metastases from digestive neuroendocrine tumor were treated with TACE (mean of 3.6 sessions) before any non-surgical treatment (somatostatin analogue, chemotherapy or interferon). Liver involvement was less than 50% in 11 patients. Size of the largest lesion ranged from 1.5 to 10 cm. Ten patients presented with carcinoid symptoms. The TACE was performed with Doxorubicin emulsified in Lipiodol and gelatin sponge particles. Symptomatic response upon flushes and/or diarrhea was complete in 7 of 10 cases and partial in 2 of 10 cases. An objective morphologic response was noted in 12 of 14 cases. The 5- and 10-year survival rate from diagnosis was 83 and 56%, respectively. Six patients were alive at the end of the study after 27-100 months from first TACE and 38-142 months from diagnosis. Three of them were successfully palliated for 55, 69, and 100 months with only TACE as treatment. Long-term palliation is possible in unresectable liver metastases from digestive neuroendocrine tumors with a few sessions of TACE as first-line and eventually exclusive treatment. (orig.)

  9. First-line treatment with cephalosporins in spontaneous bacterial peritonitis provides poor antibiotic coverage

    DEFF Research Database (Denmark)

    Novovic, Srdan; Semb, Synne; Olsen, Henrik

    2012-01-01

    Abstract Objective. Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial...... resistance in Denmark. Material and Methods. All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study. Results. One...

  10. Modification of First-line Antiretroviral Therapy in Treatment-naive, HIV Positive Patients

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    Smita Shenoy

    2017-10-01

    Full Text Available Introduction: Modification of initial Antiretroviral Therapy (ART program is an important issue in HIV infected patients as the number of ART regimens available is limited. Hence, there is a need to understand the factors that affect modification and therefore, the durability of the initial antiretroviral regimen. Aim: To study the type of modification of first line ART in treatment-naive HIV positive patients and factors influencing it. Materials and Methods: A retrospective observational study was carried out in the HIV clinic of a tertiary care hospital, using data obtained from the case records of the subjects who were initiated on ART between January 2012 to December 2014. Data on patient baseline characteristics, proportion of patients who required modification, type and time of modification was collected. The determinants of time to modification were analysed using Chi-square test. Binomial logistic regression was utilized to assess independent risk factors for change in regimen. Results: Out of 200 case records analysed, 54 patients had to undergo a modification in their initial regimen. The mean age of patients was 44.68 ± 11.31 years. Majority of the patients were males. The most common reason for modification was Adverse Drug Reactions (ADRs (79.63% followed by treatment failure (9.25%. In 85.18% cases, modification involved substitution. Occurrence of ADRs and non-tenofovir based first-line regimens were associated with higher likelihood of substitution in regimen (p<0.05. The median time (IQR to modification was 173 (152.25, 293.50 days. Conclusion: ADRs and the use of non-tenofovir based regimens resulted in significantly higher rates of modification of antiretroviral therapy. There should be monitoring of patients on ART to detect ADRs at the earliest and to obtain increased use of single tablet containing tenofovir based regimen to improve durability of first line regimens.

  11. First-line targeted therapies in the treatment of metastatic colorectal cancer – role of cetuximab

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    Giuseppe Tonini

    2009-04-01

    Full Text Available Giuseppe Tonini, Alice Calvieri, Bruno Vincenzi, Daniele SantiniMedical Oncology, University Campus Bio-Medico, Rome, ItalyAbstract: Worldwide, colorectal cancer (CRC is the fourth most commonly diagnosed malignant disease and the second leading cause of cancer-related death in Western nations. In 2008 there were an estimated 148,810 new cases and 49,960 deaths in the US. For several years different chemotherapeutic regimens, based on floropyrimidines, irinotecan and oxaliplatin, have been used in advanced CRC, but survival is still unsatisfactory. New targeted therapies, including drugs and monoclonal antibodies (MoABs , show great promise in the fight against CRC and have shown activity in different disease settings. Cetuximab, a chimeric IgG1 monoclonal antibody that binds to the extracellular domain of epidermal growth factor receptor (EGFR, is active in metastatic colorectal cancer (mCRC. As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. The combination of this drug with classical chemotherapies has shown better clinical profiles reflected in an improvement in overall and progression-free survival. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. Whereas cetuximab has a clear indication in the salvage setting, its role in first-line therapy remains investigational. It is particularly encouraging that cetuximab may enhance curative opportunities in patients with early metastatic disease, suggesting that adding cetuximab in first-line therapy may downstage disease in some patients, and, as a result, allow potentially curative resection of previously unresectable metastases. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit, and the role of cetuximab in first-line treatment of metastatic CRC

  12. FIRST-LINE TREATMENT IN PATIENTS WITH INOPERABLE METASTATIC COLON CANCER

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    M. Yu. Fedyanin

    2014-01-01

    Full Text Available First-line therapy for metastatic colon cancer is most important for a patient. Its median time to progression constitutes the bulk of the patient’s survival. Clearly, it is necessary to choose the most effective combinations of targeted drugs and chemotherapy regimens. The choice of therapy for patients with colon cancer is governed by both the clinical characteristics of the disease and the molecular changes of a tumor. In recent literature, there has been a great deal of evidence for the use of targeted drugs in different clinical situations; the results of comparative trials of different treatment combinations have been published. This all determines the reconsideration of the choice of a treatment regimen in patients with metastatic colon cancer; it is the topic of the present review.

  13. Efficacy and safety of combinations of first-line topical treatments in chronic plaque psoriasis: a systematic literature review

    NARCIS (Netherlands)

    Hendriks, A.G.M.; Keijsers, R.R.M.C.; Jong, E.M.G.J. de; Seyger, M.M.B.; Kerkhof, P.C.M. van de

    2013-01-01

    Background Most psoriasis patients suffering from mild to moderate disease are treated with first-line topical treatments, including corticosteroids, vitamin D analogues, topical retinoids and calcineurin inhibitors. Although evidence-based guidelines on combinations are lacking, the majority of

  14. New developments in cognitive behavioral therapy as the first-line treatment of insomnia

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    Allison T Siebern

    2011-02-01

    Full Text Available Allison T Siebern, Rachel ManberSleep Medicine Center, Stanford University School of Medicine, Redwood City, California, USAAbstract: Insomnia is the most common sleep disorder. Psychological, behavioral, and biological factors are implicated in the development and maintenance of insomnia as a disorder, although the etiology of insomnia remains under investigation, as it is still not fully understood. Cognitive behavioral therapy for insomnia (CBTI is a treatment for insomnia that is grounded in the science of behavior change, psychological theories, and the science of sleep. There is strong empirical evidence that CBTI is effective. Recognition of CBTI as the first-line treatment for chronic insomnia (National Institutes of Health consensus, British Medical Association was based largely on evidence of its efficacy in primary insomnia. The aim of this article is to provide background information and review recent developments in CBTI, focusing on three domains: promising data on the use of CBTI when insomnia is experienced in the presence of comorbid conditions, new data on the use of CBTI as maintenance therapy, and emerging data on the delivery of CBTI through the use of technology and in primary care settings.Keywords: insomnia, CBTI, nonpharmacological treatment

  15. Introduction of dermatome shaving as first line treatment of chronic tattoo reactions.

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    Sepehri, Mitra; Jørgensen, Bo; Serup, Jørgen

    2015-10-01

    Chronic tattoo reactions requiring treatment have increased. Laser removal is not ideal for removal of allergic reactions. Surgical removal of culprit pigment situated in the outer dermis by dermatome shaving is rational and need to be revisited. Fifty four tattoos with chronic reactions in 50 patients were treated with dermatome shaving. Tattoos with red/red nuances dominated the material. In total, 52 operations were performed in infiltration and 2 in general anaesthesia. Shaving was performed to the level in the dermis free of tattoo pigment as assessed visually by the surgeon. Operative complications were few. Healing occurred over weeks as normal for this procedure. On a rating scale from 0 to 4, 4 as most severe, the patient's severity rating of symptoms in their tattoo declined from 3.2 pre-operatively to 1.0, 0.8 and 0.7 after 3, 6 and 12 months, respectively. Burden of operation was rated low. Patient satisfaction was high. Dermatome shaving is efficient and with few complications, and is proposed as first line treatment of chronic tattoo reactions. Shaving of such reactions apparently has been neglected during enthusiastic introduction of laser approaches, which in the treatment of allergic tattoo reactions may be relatively contra indicated and of special risk.

  16. First-line HIV treatment: evaluation of backbone choice and its budget impact

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    Orietta Zaniolo

    2013-06-01

    Full Text Available OBJECTIVE: The gradual increase of persons living with HIV, mainly due to the reduced mortality achieved with effective antiretroviral therapies, calls for increased rationality and awareness in health resources consumption also during the early illness phases. Aim of this work is the estimation of the budget impact related to the variation in backbone prescribing trends in naïve patients.METHODS: Target population is the number of patients starting antiretroviral therapy each year, according to the Italian HIV surveillance registry, excluding patients receiving non-authorized or non-recommended regimens. We modeled 3-year mortality and durability rates on a dynamic cohort, basing on international literature. A prevalent patients analysis has also been conducted, for which the model is fed by a closed cohort consisting of all the patients without experience of virologic failure. The aim of this collateral analysis is to estimate the difference in current annual expenditures if the past prescription trends for patients starting therapy would have led to the evaluated hypothetical scenarios. Current Italian market shares of triple regimens containing first-choice or alternative backbones (tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine are compared to three hypothetical scenarios (base-case, minimum and maximum in which increasing shares of patients eligible to abacavir/lamivudine start first line treatment with this backbone. Annual cost for each regimen comprises drugs acquisition under hospital pricing rules, monitoring exams and preventive tests, valued basing on regional reimbursement tariffs.RESULTS: According to current prescribing trends, in the next three years about 13,000 patients starting HIV therapy will receive tenofovir/emtricitabine (83% of the target population, and minor portions other regimens (9% abacavir/lamivudine, 8% zidovudine/lamivudine. Patients that would be eligible to

  17. Ketamine as a first-line treatment for severely agitated emergency department patients.

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    Riddell, Jeff; Tran, Alexander; Bengiamin, Rimon; Hendey, Gregory W; Armenian, Patil

    2017-07-01

    Emergency physicians often need to control agitated patients who present a danger to themselves and hospital personnel. Commonly used medications have limitations. Our primary objective was to compare the time to a defined reduction in agitation scores for ketamine versus benzodiazepines and haloperidol, alone or in combination. Our secondary objectives were to compare rates of medication redosing, vital sign changes, and adverse events in the different treatment groups. We conducted a single-center, prospective, observational study examining agitation levels in acutely agitated emergency department patients between the ages of 18 and 65 who required sedation medication for acute agitation. Providers measured agitation levels on a previously validated 6-point sedation scale at 0-, 5-, 10-, and 15-min after receiving sedation. We also assessed the incidence of adverse events, repeat or rescue medication dosing, and changes in vital signs. 106 patients were enrolled and 98 met eligibility criteria. There was no significant difference between groups in initial agitation scores. Based on agitation scores, more patients in the ketamine group were no longer agitated than the other medication groups at 5-, 10-, and 15-min after receiving medication. Patients receiving ketamine had similar rates of redosing, changes in vital signs, and adverse events to the other groups. In highly agitated and violent emergency department patients, significantly fewer patients receiving ketamine as a first line sedating agent were agitated at 5-, 10-, and 15-min. Ketamine appears to be faster at controlling agitation than standard emergency department medications. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis.

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    Harrington, Rachel; Lee, Edward; Yang, Hongbo; Wei, Jin; Messali, Andrew; Azie, Nkechi; Wu, Eric Q; Spalding, James

    2017-01-01

    Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective. An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome. Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients. Astellas Pharma Global Development, Inc.

  19. Rituximab as a first-line agent for the treatment of dermatomyositis.

    LENUS (Irish Health Repository)

    2012-02-01

    B cells may play a pivotal role in the pathophysiology of DM, and reports have claimed that targeting B cells is a viable treatment option in patients with dermatomyositis. A 20-year-old girl presented in October 2007, with few weeks\\' history of proximal muscle weakness. Gottron\\'s papules were noted on her knuckles. She had normal inflammatory markers and negative autoantibody screen. Her CPK was 7,000 U\\/L (normal range 0-170) with an LDH of 1,300 U\\/L (normal range 266-500). EMG and muscle biopsy was consistent with active myositis. She had normal pulmonary function tests. HRCT showed no interstitial lung disease. She was started with 60 mg glucocorticoids (1 mg\\/kg), with a good clinical response. However, any attempt to taper down the steroid dose led to recurrence of her symptoms. The options of available immunosuppressive therapies, including the experimental usage of rituximab, were discussed with her; averse to long-term systemic treatments, she opted to try a course of rituximab. She had rituximab 1,000 mg on days 0 and 14, and her glucocorticoids were tapered in next few weeks. Now, 24 months since her rituximab infusions, she remains in complete clinical and biochemical remission and is naive to other immunosuppressive agents apart from glucocorticoids and rituximab. Depleting peripheral B cells with rituximab (one course) in our patient has led not only to complete resolution of muscle and skin disease (induction) but also remains off all immunosuppressives including glucocorticoids.

  20. The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation

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    Aronsson, Mattias; Walfridsson, Håkan; Janzon, Magnus

    2014-01-01

    AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model......, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain...... of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness...

  1. Biofeedback as a first-line treatment for overactive bladder syndrome refractory to standard urotherapy in children.

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    Ebiloglu, Turgay; Kaya, Engin; Köprü, Burak; Topuz, Bahadır; Irkilata, Hasan Cem; Kibar, Yusuf

    2016-10-01

    Overactive bladder syndrome (OAB) and dysfunctional voiding (DV) are subgroups of lower urinary tract dysfunction (LUTD). Standard urotherapy is the first-line treatment option of OAB in children. The aim was to investigate the use of biofeedback as a first-line treatment option in OAB refractory to standard urotherapy, and determine the factors affecting efficacy. Between 2005 and 2015, we retrospectively analyzed a total of 136 hospital records of children with OAB who had not previously used any anticholinergics and were refractory to standard urotherapy. Patients with urgency and/or urge incontinence and/or making holding maneuvers to suppress urgency were defined as having OAB symptoms, and resolution of these complaints was defined as successful biofeedback therapy. Seventy-three of 136 OAB patients' urgency recovered by biofeedback therapy with the success rate of 53% (p biofeedback therapies, respectively (p Biofeedback can be thought of as the first-line treatment option when standard urotherapy fails in children with OAB. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  2. Successful Treatment of Liver Aspergilloma by Caspofungin Acetate First-Line Therapy in a Non-Immunocompromised Patient

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    Hong-Juan Dong

    2012-09-01

    Full Text Available Aspergillosis remains to be a life-threatening complication in immunocompromised patients. However, Aspergillus infection can be observed in non-immunocompromised individuals in rare cases. We report a case of liver aspergilloma in a chronic aplastic anemia patient under relatively intact immune status. Therapeutic strategy for this rare condition was extensively discussed and caspofungin acetate single agent first-line therapy was applied after careful consideration. Encouraging clinical and radiologic improvements were achieved in response to the antifungal salvage. Our long-term follow-up study also revealed a favorable prognosis. Based on this experience, we suggest caspofungin acetate as first-line therapy for treatment plans of liver aspergilloma.

  3. Sequential treatment of icotinib after first-line pemetrexed in advanced lung adenocarcinoma with unknown EGFR gene status.

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    Zheng, Yulong; Fang, Weijia; Deng, Jing; Zhao, Peng; Xu, Nong; Zhou, Jianying

    2014-07-01

    In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is an important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors (TKI) in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS. We analyzed 38 patients with advanced lung adenocarcinoma with UN-EGFR-GS treated with first-line pemetrexed-based chemotherapy followed by icotinib as maintenance or second-line therapy. The response rates to pemetrexed and icotinib were 21.1% and 42.1%, respectively. The median overall survival was 27.0 months (95% CI, 19.7-34.2 months). The 12-month overall survival probability was 68.4%. The most common toxicities observed in icotinib phase were rashes, diarrheas, and elevated aminotransferase. Subgroup analysis indicated that the overall survival is correlated with response to icotinib. The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China.

  4. Aspirin is first-line treatment for migraine and episodic tension-type headache regardless of headache intensity.

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    Lampl, Christian; Voelker, Michael; Steiner, Timothy J

    2012-01-01

    (1) To establish whether pre-treatment headache intensity in migraine or episodic tension-type headache (ETTH) predicts success or failure of treatment with aspirin; and (2) to reflect, accordingly, on the place of aspirin in the management of these disorders. Stepped care in migraine management uses symptomatic treatments as first-line, reserving triptans for those in whom this proves ineffective. Stratified care chooses between symptomatic therapy and triptans as first-line on an individual basis according to perceived illness severity. We questioned the 2 assumptions underpinning stratified care in migraine that greater illness severity: (1) reflects greater need; and (2) is a risk factor for failure of symptomatic treatment but not of triptans. With regard to the first assumption, we developed a rhetorical argument that need for treatment is underpinned by expectation of benefit, not by illness severity. To address the second, we reviewed individual patient data from 6 clinical trials of aspirin 1000 mg in migraine (N = 2079; 1165 moderate headache, 914 severe) and one of aspirin 500 and 1000 mg in ETTH (N = 325; 180 moderate, 145 severe), relating outcome to pre-treatment headache intensity. In migraine, for headache relief at 2 hours, a small (4.7%) and non-significant risk difference (RD) in therapeutic gain favored moderate pain; for pain freedom at 2 hours, therapeutic gains were almost identical (RD: -0.2%). In ETTH, for headache relief at 2 hours, RDs for both aspirin 500 mg (-4.2%) and aspirin 1000 mg (-9.7%) favored severe pain, although neither significantly; for pain freedom at 2 hours, RDs (-14.2 and -3.6) again favored severe pain. In neither migraine nor ETTH does pre-treatment headache intensity predict success or failure of aspirin. This is not an arguable basis for stratified care in migraine. In both disorders, aspirin is first-line treatment regardless of headache intensity. © 2011 American Headache Society.

  5. Shortened first-line TB treatment in Brazil: potential cost savings for patients and health services

    NARCIS (Netherlands)

    Trajman, Anete; Bastos, Mayara Lisboa; Belo, Marcia; Calaça, Janaína; Gaspar, Júlia; Dos Santos, Alexandre Martins; Dos Santos, Camila Martins; Brito, Raquel Trindade; Wells, William A.; Cobelens, Frank G.; Vassall, Anna; Gomez, Gabriela B.

    2016-01-01

    Shortened treatment regimens for tuberculosis are under development to improve treatment outcomes and reduce costs. We estimated potential savings from a societal perspective in Brazil following the introduction of a hypothetical four-month regimen for tuberculosis treatment. Data were gathered in

  6. Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

    Science.gov (United States)

    Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

    2014-08-01

    A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

  7. IVF or IUI as first-line treatment in unexplained subfertility: the conundrum of treatment selection markers.

    Science.gov (United States)

    Tjon-Kon-Fat, R I; Tajik, P; Zafarmand, M H; Bensdorp, A J; Bossuyt, P M M; Oosterhuis, G J E; van Golde, R; Repping, S; Lambers, M D A; Slappendel, E; Perquin, D; Pelinck, M J; Gianotten, J; Maas, J W M; Eijkemans, M J C; van der Veen, F; Mol, B W; van Wely, M

    2017-05-01

    Are there treatment selection markers that could aid in identifying couples, with unexplained or mild male subfertility, who would have better chances of a healthy child with IVF with single embryo transfer (IVF-SET) than with IUI with ovarian stimulation (IUI-OS)? We did not find any treatment selection markers that were associated with better chances of a healthy child with IVF-SET instead of IUI-OS in couples with unexplained or mild male subfertility. A recent trial, comparing IVF-SET to IUI-OS, found no evidence of a difference between live birth rates and multiple pregnancy rates. It was suggested that IUI-OS should remain the first-line treatment instead of IVF-SET in couples with unexplained or mild male subfertility and female age between 18 and 38 years. The question remains whether there are some couples that may have higher pregnancy chances if treated with IVF-SET instead of IUI. We performed our analyses on data from the INeS trial, where couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception were randomly allocated to IVF-SET, IVF in a modified natural cycle or IUI-OS. In view of the aim of this study, we only used data of the comparison between IVF-SET (201 couples) and IUI-OS (207 couples). We pre-defined the following baseline characteristics as potential treatment selection markers: female age, ethnicity, smoking status, type of subfertility (primary/secondary), duration of subfertility, BMI, pre-wash total motile count and Hunault prediction score. For each potential treatment selection marker, we explored the association with the chances of a healthy child after IVF-SET and IUI-OS and tested if there was an interaction with treatment. Given the exploratory nature of our analysis, we used a P-value of 0.1. None of the markers were associated with higher chances of a healthy child from IVF-SET compared to IUI-OS (P-value for interaction >0.10). Since this is the first large study that looked at

  8. First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001-2012.

    Science.gov (United States)

    Bacigalupo, Andrea; Oneto, Rosi; Schrezenmeier, Hubert; Hochsmann, Britta; Dufour, Carlo; Kojima, Seiji; Zhu, Xiaofan; Chen, Xiaojuan; Issaragrisil, Surapol; Chuncharunee, Suporn; Jeong, Dae Chul; Giammarco, Sabrina; Van Lint, Maria Teresa; Zheng, Yizhou; Vallejo, Carlos

    2018-05-01

    The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10-year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10-year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis-treament and severity of the disease, remain strong predictors of response and survival. © 2018 Wiley Periodicals, Inc.

  9. New developments in cognitive behavioral therapy as the first-line treatment of insomnia

    OpenAIRE

    Siebern, Allison T; Manber, Rachel

    2011-01-01

    Allison T Siebern, Rachel ManberSleep Medicine Center, Stanford University School of Medicine, Redwood City, California, USAAbstract: Insomnia is the most common sleep disorder. Psychological, behavioral, and biological factors are implicated in the development and maintenance of insomnia as a disorder, although the etiology of insomnia remains under investigation, as it is still not fully understood. Cognitive behavioral therapy for insomnia (CBTI) is a treatment for insomnia that is grounde...

  10. Systematic review: Coca-Cola can effectively dissolve gastric phytobezoars as a first-line treatment.

    Science.gov (United States)

    Ladas, S D; Kamberoglou, D; Karamanolis, G; Vlachogiannakos, J; Zouboulis-Vafiadis, I

    2013-01-01

    Gastric phytobezoars represent the most common bezoars in patients with poor gastric motility. A variety of dissolution therapies and endoscopic fragmentation techniques have been evaluated as conservative treatment so as to avoid surgery. To investigate the effectiveness of Coca-Cola for gastric phytobezoars dissolution. We performed a systematic search to identify publications on gastric phytobezoars to assess the efficacy of Coca-Cola as a dissolution therapy. Diospyrobezoars, formed after persimmon ingestion, are a distinct type of phytobezoars characterized by their hard consistency. Thus, these two subgroups of bezoars were compared in terms of successful dissolution. Over a 10-year period (2002-2012), 24 papers including 46 patients have been published. In 91.3% of the cases, phytobezoar resolution with Coca-Cola administration was successful, either as a single treatment (50%) or combined with further endoscopic techniques, whereas only 4 patients underwent surgery. Phytobezoars were more likely to dissolve after initial attempt with Coca-Cola compared with diospyrobezoars (60.6% vs. 23%, P = 0.022). Coca-Cola alone is effective in gastric phytobezoar dissolution in half of the cases and, combined with additional endoscopic methods, is successful in more than 90% of them. © 2012 Blackwell Publishing Ltd.

  11. Diagnosis and first-line treatment of breast cancer in Italian general hospitals

    International Nuclear Information System (INIS)

    Interdisciplinary Group for Cancer Care Evaluation, Milan

    1986-01-01

    The quality of the diagnostic and therapeutic process of 1262 newly diagnosed breast cancer patients was evaluated in 63 Italian general hospital over the period March 1983 - April 1984. Most of the patients (91%) discovered their own lesion, which was a nodule in 83% of the cases. Practice of breast self examination was reported by 418 (33%) patients, only 28% of whom did that on a regular monthly basis. A diagnostic delay>3 months was present in 36% of the patients. Among the preoperative work-up examinations, skeletal X-ray or bone scan was not performed in 20% of patients, whereas other essential examinations were done in most. The Patey type of radical mastectomy was the most frequent surgical procedure; quadrantectomy was performed in only 26% of eligible patients, more frequently in younger (34%) than in older patients (21%). Adjuvant chemotherapy was recommended for 11% and 6% of pre- and postmenopausal N- patients, and for 78% and 47% of pre- and postmenopausal N+ patients. Forty-three of the 63 participating hospitals reported they adhered to the guidelines defined by the Italian Breast Cancer Task Force (F.O.N.Ca.M.) but this was not associated with substantial evidence of better quality of care. Similary, no associations emerged between several hospitals' organizational features and adherence to recommended treatment guidelines. The study is ongoing to assess the quality of postsurgical treatment and to measure its impact on patients' survival

  12. Primary stroke prevention and hypertension treatment: which is the first-line strategy?

    Science.gov (United States)

    Ravenni, Roberta; Jabre, Joe F; Casiglia, Edoardo; Mazza, Alberto

    2011-07-05

    Hypertension (HT) is considered the main classic vascular risk factor for stroke and the importance of lowering blood pressure (BP) is well established. However, not all the benefit of antihypertensive treatment is due to BP reduction per se, as the effect of reducing the risk of stroke differs among classes of antihypertensive agents. Extensive evidences support that angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), dihydropyridine calcium channel blockers (CCB) and thiazide diuretics each reduced risk of stroke compared with placebo or no treatment. Therefore, when combination therapy is required, a combination of these antihypertensive classes represents a logical approach. Despite the efficacy of antihypertensive therapy a large proportion of the population, still has undiagnosed or inadequately treated HT, and remain at high risk of stroke. In primary stroke prevention current guidelines recommend a systolic/diastolic BP goal of market of the fixed-dose combination (FDC) of ACEI or ARB and CCB should provide a better control of BP. However to confirm the efficacy of the FDC in primary stroke prevention, clinical intervention trials are needed.

  13. Introduction of dermatome shaving as first line treatment of chronic tattoo reactions

    DEFF Research Database (Denmark)

    Sepehri, Mitra; Jørgensen, Bo; Serup, Jørgen

    2015-01-01

    BACKGROUND/AIMS: Chronic tattoo reactions requiring treatment have increased. Laser removal is not ideal for removal of allergic reactions. Surgical removal of culprit pigment situated in the outer dermis by dermatome shaving is rational and need to be revisited. MATERIALS/METHODS: Fifty four...... tattoos with chronic reactions in 50 patients were treated with dermatome shaving. Tattoos with red/red nuances dominated the material. In total, 52 operations were performed in infiltration and 2 in general anaesthesia. Shaving was performed to the level in the dermis free of tattoo pigment as assessed...... visually by the surgeon. RESULTS: Operative complications were few. Healing occurred over weeks as normal for this procedure. On a rating scale from 0 to 4, 4 as most severe, the patient's severity rating of symptoms in their tattoo declined from 3.2 pre-operatively to 1.0, 0.8 and 0.7 after 3, 6 and 12...

  14. Renal Artery Embolization - A First Line Treatment Option For End-Stage Hydronephrosis

    International Nuclear Information System (INIS)

    Mitra, Kakali; Prabhudesai, Vikramaditya; James, R. Lester; Jones, Robert W. A.; French, Michael E.; Cowling, Mark; West, David J.

    2004-01-01

    Conventionally poorly functioning hydronephrotic kidneys have been removed if they are symptomatic. In our unit, patients are offered renal artery embolization as an alternative treatment option. Patients and Methods: Fifteen patients (11 male, 4 female) with a mean age of 32.9 yr (20-51 yrs) have undergone renal artery embolization for symptomatic hydronephrosis with poor function. Mean follow-up was 64.13 weeks (range 14-200). All patients had loin pain and hydronephrosis. Twelve patients had primary pelvi-ureteric junction obstruction (PUJO). Two patients had poorly functioning hydronephrotic kidneys secondary to chronic calculous obstruction. One patient had chronic pain in an obstructed but reasonably functioning kidney following a previous pyeloplasty for PUJO which demanded intervention. Mean split function on renography was 11% (range 0-46%). Selective renal artery embolization was carried out under antibiotic cover using a 7 Fr balloon occlusion catheter and absolute alcohol, steel coils, and polyvinyl alcohol particles.Results: Nine patients developed post-embolization syndrome of self-limiting pain and pyrexia with no evidence of sepsis. One patient required readmission with this condition. One patient developed a hematoma at the puncture site. Mean hospital stay was 2.3 days. Fourteen patients are happy with the result and are completely pain free. One patient has minor discomfort but is delighted with the result. Nine patients have had follow-up ultrasound confirming resolution of the hydronephrosis. Conclusion: Renal artery embolization is an effective, safe, well-tolerated minimally invasive treatment option in end-stage hydronephrosis and we routinely offer it as an alternative to nephrectomy

  15. Onyx embolization as a first line treatment for intracranial dural arteriovenous fistulas with cortical venous reflux

    International Nuclear Information System (INIS)

    Panagiotopoulos, V.; Forsting, M.; Wanke, I.; Moeller-Hartmann, W.; Asgari, S.; Sandalcioglu, I.E.

    2009-01-01

    Our purpose was to present our experience regarding embolization of intracranial dural arteriovenous fistulas (DAVFs) with cortical venous reflux using Onyx, a non-adhesive liquid embolic agent. From January 2006 to December 2007, 16 patients (12 men and 4 women) with a mean age of 61 years (range 42 - 78) with an intracranial DAVF with cortical venous reflux underwent at least one transarterial embolization using Onyx. According to the Cognard classification, 2 lesions were grade V, 5 were grade IV, 6 were grade III, 2 were grade IIa+b, and 1 was grade IIb. The clinical presentation included 5 hemorrhagic deficits, 10 non-hemorrhagic manifestations, and 1 patient was asymptomatic. Twenty-four embolization sessions were performed in 16 patients with an average of 3 arterial feeders (range 1 - 9) embolized per DAVF. Immediately after embolization, complete occlusion was achieved in 9 / 16 (56 %) patients after the first session. Further postembolization surgical treatment was performed in 3 patients. Partial reperfusion occurred in 1 patient at the time of mean follow-up of 3.7 months (range 0 - 12). Treatment has been completed for 11 / 16 patients with angiographic cure in 10 / 11 (91 %). An infratentorial bleeding complication related to embolization occurred in one patient with temporary worsening of the patient's gait disturbance. At the time of mean clinical follow-up of 4.5 months (range 0 - 12), no procedure-related permanent morbidity was added to our cohort. According to our experience, embolization of intracranial DAVFs with cortical venous drainage using Onyx is feasible with promising results, indicating stability at the time of mid-term follow-up. In very complex DAVFs additional embolization material might be necessary, and in some cases surgery is warranted. (orig.)

  16. Management of calculus anuria using ureteroscopic lithotripsy as a first line treatment: its efficacy and safety.

    Science.gov (United States)

    Savić, Slaviša; Vukotić, Vinka; Lazić, Miodrag; Savić, Nataša

    2014-05-06

    To present our experience with emergency ureteroscopic lithotripsy (URSL) for ureteral calculi associated with acute kidney injury (AKI). We retrospectively evaluated the 61 patients consisted of 90 ureteral units (UU), who underwent URSL. The cause of anuria was bilateral calculus obstructions in 29 cases, and unilateral calculus obstruction with, absent, nephrectomized contralateral kidney in 32 cases. In the case of bilateral synchronous ureteric calculi same-session bilateral ureteroscopy (SBBU) was done. The duration of anuria varied between 12 to 72 hours. At the end of the procedure, ureteral stent was systematically left in place in all patients. Surgery was performed 6-12 hours after admission to hospital. Patients were followed at least 1 month postoperatively. The stone free rates (SFR) were determined as baseline, on the first post-operative day, and as overall on the 30 days after procedure. The greatest success was achieved in the distal localization of stones up to 10 mm (93%). Renal function returned in 51 (83.6%) patients within 7 days. In 18 (29.5%) patients [18 (20%) UU] we performed second procedure as extracorporeal shockwave lithotripsy in 16.7% and open surgery in 2.2%. In 43 (70.5%) patients URSL was a successful therapeutic approach in dealing with pain, obstruction and calculus. Calculus anuria is a medical emergency that requires rapid diagnosis and prompt treatment for the purpose of decompression. URSL is the proper method of choice for selected patients and can be performed safely and has high success rates with minimal morbidity.

  17. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial.

    Science.gov (United States)

    Argilés, Guillem; Saunders, Mark P; Rivera, Fernando; Sobrero, Alberto; Benson, Al; Guillén Ponce, Carmen; Cascinu, Stefano; Van Cutsem, Eric; Macpherson, Iain R; Strumberg, Dirk; Köhne, Claus-Henning; Zalcberg, John; Wagner, Andrea; Luigi Garosi, Vittorio; Grunert, Julia; Tabernero, Josep; Ciardiello, Fortunato

    2015-05-01

    The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Regorafenib+mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. Copyright © 2015. Published by Elsevier Ltd.

  18. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma

    Science.gov (United States)

    Russell, Jeffery; Lebbé, Céleste; Chmielowski, Bartosz; Gambichler, Thilo; Grob, Jean-Jacques; Kiecker, Felix; Rabinowits, Guilherme; Terheyden, Patrick; Zwiener, Isabella; Bajars, Marcis; Hennessy, Meliessa; Kaufman, Howard L.

    2018-01-01

    Importance Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti–programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). Objective To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC. Design, Setting, and Participants JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Interventions Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Main Outcomes and Measures Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. Results As of March 24, 2017, 39 patients were enrolled (30 men and 9 women; median age, 75 years [range, 47-88 years]), with a median follow-up of 5.1 months (range, 0.3-11.3 months). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up; the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing

  19. Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance.

    Science.gov (United States)

    Cosme, Angel; Montes, Milagrosa; Ibarra, Begoña; Tamayo, Esther; Alonso, Horacio; Mendarte, Usua; Lizasoan, Jacobo; Herreros-Villanueva, Marta; Bujanda, Luis

    2017-05-14

    To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance. A total of 1034 patients infected by Helicobacter pylori ( H. pylori ) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori -resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori -resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. Intention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.

  20. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients

    International Nuclear Information System (INIS)

    Maréchal, Raphaël; De Schutter, Jef; Nagy, Nathalie; Demetter, Pieter; Lemmers, Arnaud; Devière, Jacques; Salmon, Isabelle; Tejpar, Sabine; Van Laethem, Jean-Luc

    2010-01-01

    Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown. We assessed immune cells infiltrate (CD56, CD68, CD3, CD4, CD8, Foxp3) in the primary tumor of metastatic colorectal cancer (mCRC) patients treated with a first-line cetuximab-based chemotherapy in the framework of prospective trials (treatment group) and in a matched group of mCRC patients who received the same chemotherapy regimen without cetuximab (control group). The relationship between intra-tumoral immune effector cells, the K-ras status and the efficacy of the treatment were investigated. We also evaluated in vitro, the ADCC activity in healthy donors and chemonaive mCRC patients and the specific contribution of CD56 + cells. ADCC activity against DLD1 CRC cell line is maintained in cancer patients and significantly declined after CD56 + cells depletion. In multivariate analysis, K-ras wild-type (HR: 4.7 (95% CI 1.8-12.3), p = 0.001) and tumor infiltrating CD56 + cells (HR: 2.6, (95%CI:1.14-6.0), p = 0.019) were independent favourable prognostic factors for PFS and response only in the cetuximab treatment group. By contrast CD56 + cells failed to predict PFS and response in the control group. CD56 + cells, mainly NK cells, may be the major effector of ADCC related-cetuximab activity. Assessment of CD56 + cells infiltrate in primary colorectal adenocarcinoma may provide additional information to K-ras status in predicting response and PFS in mCRC patients treated with first-line cetuximab-based chemotherapy

  1. First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Gupta N

    2013-12-01

    Full Text Available Neha Gupta, Hassan Hatoum, Grace K DyDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USAAbstract: Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007 is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel. A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.Keywords: ABI-007, Abraxane, nab

  2. Immunotherapy “Shock” a case series of PD-L1 100% and pembrolizumab first-line treatment

    Directory of Open Access Journals (Sweden)

    Paul Zarogoulidis

    2017-01-01

    Full Text Available In this decade a “bloom” of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression.

  3. Uterine Artery Embolization for Retained Products of Conception with Marked Vascularity: A Safe and Efficient First-Line Treatment

    International Nuclear Information System (INIS)

    Bazeries, Paul; Paisant-Thouveny, Francine; Yahya, Sultan; Bouvier, Antoine; Nedelcu, Cosmina; Boussion, Francoise; Sentilhes, Loic; Willoteaux, Serge; Aubé, Christophe

    2017-01-01

    ObjectiveTo report our clinical practice regarding a case series of retained products of conception (RPOC) with marked vascularity (MV) managed with selective uterine artery embolization (UAE) as first-line treatment.MethodsThis was a monocentric, retrospective study of 31 consecutive cases of RPOC with MV diagnosed by Doppler ultrasound in the context of postpartum/postabortal bleeding. The primary outcome was the absence of rebleeding following embolization.ResultsRPOC with MV occurred after abortion in 27 out of 31 patients (87%). The time elapsed between delivery/abortion and UAE ranged from 1 to 210 days (mean 55.7 ± 45 days). Primary clinical success was achieved in 23 women (74.2%) following a single embolization. In total, 27 out of 31 women (87%) had been exclusively managed by UAE with conservative success. Although procedural success was achieved in this number, six women had a further procedure to evacuate RPOC despite procedural success. Large uterine arteriovenous (AV) shunts associated with RPOC were observed in five cases (16.1%), among which two were successfully treated after a single UAE and one after two UAEs, while hysterectomy was performed in the last two cases despite two and three UAE procedures respectively. RPOC was histologically proven in ten cases (32.2%) including four out of five cases of uterine AV shunt.ConclusionRPOC with MV can present with large uterine AV shunt, particularly in case of late management. Uterine artery embolization is an effective and safe first-line treatment, and should be evaluated for this indication in larger prospective trials.

  4. Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Noemí Reguart

    2010-06-01

    Full Text Available Noemí Reguart1, Andrés Felipe Cardona2, Rafael Rosell31Medical Oncology Service, ICMHO, Hospital Clinic Barcelona, Barcelona, Spain; 2Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, D.C., Colombia; 3Medical Oncology Service, Catalan Institute of Oncology, ICO, Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainAbstract: Erlotinib hydrochloride (Tarceva® is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR, with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents.Keywords: erlotinib, tyrosine kinase inhibitors, first line, maintenance, non-small-cell lung cancer

  5. Uterine Artery Embolization for Retained Products of Conception with Marked Vascularity: A Safe and Efficient First-Line Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bazeries, Paul, E-mail: paul.bazeries@chu-angers.fr; Paisant-Thouveny, Francine; Yahya, Sultan; Bouvier, Antoine; Nedelcu, Cosmina [Centre Hospitalier Universitaire d’Angers, Département d’Imagerie Diagnostique et interventionnelle (France); Boussion, Francoise; Sentilhes, Loic [Centre Hospitalier Universitaire d’Angers, Département de Gynécologie et Obstétrique (France); Willoteaux, Serge; Aubé, Christophe [Centre Hospitalier Universitaire d’Angers, Département d’Imagerie Diagnostique et interventionnelle (France)

    2017-04-15

    ObjectiveTo report our clinical practice regarding a case series of retained products of conception (RPOC) with marked vascularity (MV) managed with selective uterine artery embolization (UAE) as first-line treatment.MethodsThis was a monocentric, retrospective study of 31 consecutive cases of RPOC with MV diagnosed by Doppler ultrasound in the context of postpartum/postabortal bleeding. The primary outcome was the absence of rebleeding following embolization.ResultsRPOC with MV occurred after abortion in 27 out of 31 patients (87%). The time elapsed between delivery/abortion and UAE ranged from 1 to 210 days (mean 55.7 ± 45 days). Primary clinical success was achieved in 23 women (74.2%) following a single embolization. In total, 27 out of 31 women (87%) had been exclusively managed by UAE with conservative success. Although procedural success was achieved in this number, six women had a further procedure to evacuate RPOC despite procedural success. Large uterine arteriovenous (AV) shunts associated with RPOC were observed in five cases (16.1%), among which two were successfully treated after a single UAE and one after two UAEs, while hysterectomy was performed in the last two cases despite two and three UAE procedures respectively. RPOC was histologically proven in ten cases (32.2%) including four out of five cases of uterine AV shunt.ConclusionRPOC with MV can present with large uterine AV shunt, particularly in case of late management. Uterine artery embolization is an effective and safe first-line treatment, and should be evaluated for this indication in larger prospective trials.

  6. Modeling and simulation of maintenance treatment in first-line non-small cell lung cancer with external validation

    International Nuclear Information System (INIS)

    Han, Kelong; Claret, Laurent; Sandler, Alan; Das, Asha; Jin, Jin; Bruno, Rene

    2016-01-01

    Maintenance treatment (MTx) in responders following first-line treatment has been investigated and practiced for many cancers. Modeling and simulation may support interpretation of interim data and development decisions. We aimed to develop a modeling framework to simulate overall survival (OS) for MTx in NSCLC using tumor growth inhibition (TGI) data. TGI metrics were estimated using longitudinal tumor size data from two Phase III first-line NSCLC studies evaluating bevacizumab and erlotinib as MTx in 1632 patients. Baseline prognostic factors and TGI metric estimates were assessed in multivariate parametric models to predict OS. The OS model was externally validated by simulating a third independent NSCLC study (n = 253) based on interim TGI data (up to progression-free survival database lock). The third study evaluated pemetrexed + bevacizumab vs. bevacizumab alone as MTx. Time-to-tumor-growth (TTG) was the best TGI metric to predict OS. TTG, baseline tumor size, ECOG score, Asian ethnicity, age, and gender were significant covariates in the final OS model. The OS model was qualified by simulating OS distributions and hazard ratios (HR) in the two studies used for model-building. Simulations of the third independent study based on interim TGI data showed that pemetrexed + bevacizumab MTx was unlikely to significantly prolong OS vs. bevacizumab alone given the current sample size (predicted HR: 0.81; 95 % prediction interval: 0.59–1.09). Predicted median OS was 17.3 months and 14.7 months in both arms, respectively. These simulations are consistent with the results of the final OS analysis published 2 years later (observed HR: 0.87; 95 % confidence interval: 0.63–1.21). Final observed median OS was 17.1 months and 13.2 months in both arms, respectively, consistent with our predictions. A robust TGI-OS model was developed for MTx in NSCLC. TTG captures treatment effect. The model successfully predicted the OS outcomes of an independent study based on interim

  7. Modeling and simulation of maintenance treatment in first-line non-small cell lung cancer with external validation.

    Science.gov (United States)

    Han, Kelong; Claret, Laurent; Sandler, Alan; Das, Asha; Jin, Jin; Bruno, Rene

    2016-07-13

    Maintenance treatment (MTx) in responders following first-line treatment has been investigated and practiced for many cancers. Modeling and simulation may support interpretation of interim data and development decisions. We aimed to develop a modeling framework to simulate overall survival (OS) for MTx in NSCLC using tumor growth inhibition (TGI) data. TGI metrics were estimated using longitudinal tumor size data from two Phase III first-line NSCLC studies evaluating bevacizumab and erlotinib as MTx in 1632 patients. Baseline prognostic factors and TGI metric estimates were assessed in multivariate parametric models to predict OS. The OS model was externally validated by simulating a third independent NSCLC study (n = 253) based on interim TGI data (up to progression-free survival database lock). The third study evaluated pemetrexed + bevacizumab vs. bevacizumab alone as MTx. Time-to-tumor-growth (TTG) was the best TGI metric to predict OS. TTG, baseline tumor size, ECOG score, Asian ethnicity, age, and gender were significant covariates in the final OS model. The OS model was qualified by simulating OS distributions and hazard ratios (HR) in the two studies used for model-building. Simulations of the third independent study based on interim TGI data showed that pemetrexed + bevacizumab MTx was unlikely to significantly prolong OS vs. bevacizumab alone given the current sample size (predicted HR: 0.81; 95 % prediction interval: 0.59-1.09). Predicted median OS was 17.3 months and 14.7 months in both arms, respectively. These simulations are consistent with the results of the final OS analysis published 2 years later (observed HR: 0.87; 95 % confidence interval: 0.63-1.21). Final observed median OS was 17.1 months and 13.2 months in both arms, respectively, consistent with our predictions. A robust TGI-OS model was developed for MTx in NSCLC. TTG captures treatment effect. The model successfully predicted the OS outcomes of an independent study

  8. Genetic variants as ovarian cancer first-line treatment hallmarks: A systematic review and meta-analysis.

    Science.gov (United States)

    Assis, Joana; Pereira, Carina; Nogueira, Augusto; Pereira, Deolinda; Carreira, Rafael; Medeiros, Rui

    2017-12-01

    The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer pharmacogenetic studies to update and summarize the available data and to provide directions for further research. A systematic review followed by a meta-analysis was conducted on cohort studies assessing the involvement of genetic polymorphisms in ovarian cancer first-line treatment response retrieved through a MEDLINE database search by November 2016. Studies were pooled and summary estimates and 95% confidence intervals (CI) were calculated using random or fixed-effects models as appropriate. One hundred and forty-two studies gathering 106871 patients were included. Combined data suggested that GSTM1-null genotype patients have a lower risk of death compared to GSTM1-wt carriers, specifically in advanced stages (hazard ratio (HR), 0.68; 95% CI, 0.48-0.97) and when submitted to platinum-based chemotherapy (aHR, 0.61; 95% CI, 0.39-0.94). ERCC1 rs11615 and rs3212886 might have also a significant impact in treatment outcome (aHR, 0.67; 95% CI, 0.51-0.89; aHR, 1.28; 95% CI, 1.01-1.63, respectively). Moreover, ERCC2 rs13181 and rs1799793 showed a distinct ethnic behavior (Asians: aHR, 1.41; 95% CI, 0.80-2.49; aHR, 1.07; 95% CI, 0.62-1.86; Caucasians: aHR, 0.10; 95% CI, 0.01-0.96; aHR, 0.18; 95% CI, 0.05-0.68, respectively). The definition of integrative predictive models should encompass genetic information, especially regarding GSTM1 homozygous deletion. Justifying additional pharmacogenetic investigation are variants in ERCC1 and ERCC2, which highlight the DNA Repair ability to ovarian cancer prognosis. Further knowledge could aid to understand platinum-treatment failure and to tailor chemotherapy strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Non small-cell lung cancer and treatment options after tyrosine kinase inhibitors failure in the first line

    International Nuclear Information System (INIS)

    Chowaniecova, G.

    2014-01-01

    Introduction: Advanced non-small cell lung cancer with present epidermal growth factor receptor (EGFR) sensitising mutation is standardly treated with tyrosine kinase inhibitors (TKI). During treatment a resistance to TKI develops, disease progresses. We differ primary and secondary resistance. The most effective treatment after TKI failure is not definitively proven. Standard chemotherapy is usually introduced, eventually it is possible to use other TKI in the next lines. Case: The author presents a case of 60-year old patient with lung adenocarcinoma with EGFR sensitising mutation, where primary resistance to TKI was observed. Chemotherapy after progression was introduced. Planned therapy with afatnib was not carried out due to deterioration of patient´s condition. Conclusion: Presented case of EGFR mutation-positive patient represents an example of not very frequent primary resistance to TKI. Mechanisms of primary resistance are not well understood. Treatment after first line TKI failure in non-small cell lung cancer with EGFR mutation represents a challenge for medical research. (author)

  10. [Tranexamic acid as first-line emergency treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors].

    Science.gov (United States)

    Beauchêne, C; Martins-Héricher, J; Denis, D; Martin, L; Maillard, H

    2018-05-04

    Episodes of acquired bradykinin-mediated angioedema due to angiotensin-converting enzyme (ACE) inhibitors may result in fatal outcomes. There is no consensus regarding emergency pharmacological management of these episodes. Treatment options include icatibant and C1INH concentrate. Tranexamic acid is administered for moderate episodes. Its efficacy in the treatment of ACE inhibitor-induced episodes of angioedema is not established. The aim of this retrospective study is to assess the benefits of emergency tranexamic acid administration in the management of ACE inhibitor-induced episodes of angioedema. Retrospective analysis of the medical files of patients who consulted between 2010 and 2016 in two French tertiary care hospitals for a bradykinic angioedema attributed to an ACE treatment. All of them had received tranexamic acid as a first line treatment. Thirty three patients who had experienced severe episode of angioedema were included. Twenty seven patients showed significant improvement when treated with tranexamic acid alone. The six remaining patients were treated with icatibant (5/33) or C1INH concentrate (1/33), due to partial improvement after tranexamic acid therapy. None of the patients were intubated, no fatalities were recorded and no side effects were reported. Tranexamic acid is an easily accessible and affordable therapy that may provide effective treatment for ACE inhibitor-induced episodes of angioedema. It may help while waiting for a more specific treatment (icatibant and C1INH concentrate) that is at times unavailable in emergency departments. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  11. The influence of patient beliefs and treatment satisfaction on the discontinuation of current first-line antiretroviral regimens.

    Science.gov (United States)

    Casado, J L; Marín, A; Romero, V; Bañón, S; Moreno, A; Perez-Elías, M J; Moreno, S; Rodriguez-Sagrado, M A

    2016-01-01

    Large cohort studies have shown a high rate of first-line combination antiretroviral therapy (cART) regimen discontinuation in HIV-infected patients, attributed to characteristics of the cART regimen or toxicity. A cohort study of 274 patients receiving a first-line regimen was carried out. Patients' perceptions and beliefs prior to initiation were assessed using an attitude towards medication scale (0-15 points), and their satisfaction during therapy was assessed using an HIV treatment satisfaction questionnaire (HIVTSQ). Treatment discontinuation was defined as any switch in the cART regimen. During 474.8 person-years of follow-up, 63 (23%) patients changed their cART regimen, mainly because of toxicity/intolerance (42; 67%). The overall rate of change was 13.2 per 100 patient-years [95% confidence interval (CI) 11.1-16.4 per 100 patient-years]. An efavirenz (EFV)-based single tablet regimen showed the highest rate of adverse events (27%), but the lowest rate of change (16%; 7.44 per 100 patient-years). Cox regression revealed a decreased hazard of first regimen termination with better initial attitude towards drugs [hazard ratio (HR) 0.76; 95% CI 0.62-0.93; P satisfaction (HR 0.94; 95% CI 0.89-0.99; P = 0.01), and an increased hazard of termination with the presence of adverse events (HR 7.7; 95% CI 2.4-11.6; P patients (18 of 59; 31%) with mild/moderate adverse events (which were mainly central nervous system symptoms) continued the regimen; these patients, compared with those discontinuing therapy, showed better perception of therapy (mean score 14.4 versus 12.1, respectively; P = 0.05) and greater satisfaction during therapy (mean score 50.6 versus 44.6, respectively; P = 0.04). Patients' beliefs and satisfaction with therapy influence the durability of the first antiretroviral regimen. These patient-related factors modulate the impact of mild adverse events, and could explain differences in the rate of discontinuation. © 2015 British HIV

  12. Longitudinal Analysis of Adherence to First-Line Antiretroviral Therapy: Evidence of Treatment Sustainability from an Indian HIV Cohort.

    Science.gov (United States)

    Shet, Anita; Kumarasamy, N; Poongulali, Selvamuthu; Shastri, Suresh; Kumar, Dodderi Sunil; Rewari, Bharath B; Arumugam, Karthika; Antony, Jimmy; De Costa, Ayesha; D'Souza, George

    2016-01-01

    Given the chronic nature of HIV infection and the need for life-long antiretroviral therapy (ART), maintaining long-term optimal adherence is an important strategy for maximizing treatment success. In order to understand better the dynamic nature of adherence behaviors in India where complex cultural and logistic features prevail, we assessed the patterns, trajectories and time-dependent predictors of adherence levels in relation to virological failure among individuals initiating first-line ART in India. Between July 2010 and August 2013, eligible ART-naïve HIV-infected individuals newly initiating first-line ART within the national program at three sites in southern India were enrolled and monitored for two years. ART included zidovudine/stavudine/tenofovir plus lamivudine plus nevirapine/efavirenz. Patients were assessed using clinical, laboratory and adherence parameters. Every three months, medication adherence was measured using pill count, and a structured questionnaire on adherence barriers was administered. Optimal adherence was defined as mean adherence ≥95%. Statistical analysis was performed using a bivariate and a multivariate model of all identified covariates. Adherence trends and determinants were modeled as rate ratios using generalized estimating equation analysis in a Poisson distribution. A total of 599 eligible ART-naïve patients participated in the study, and contributed a total of 921 person-years of observation time. Women constituted 43% and mean CD4 count prior to initiating ART was 192 cells/mm3. Overall mean adherence among all patients was 95.4%. The proportion of patients optimally adherent was 75.6%. Predictors of optimal adherence included older age (≥40 years), high school-level education and beyond, lower drug toxicity-related ART interruption, full disclosure, sense of satisfaction with one's own health and patient's perception of having good access to health-care services. Adherence was inversely proportional to virological

  13. Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Chouaïd C

    2014-12-01

    Full Text Available Christos Chouaïd,1 Perinne Crequit,2 Isabelle Borget,3 Alain Vergnenegre4 1Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal Créteil et Université de Paris Est Créteil, Paris, France; 2Service de Pneumologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France; 3Service de Biostatistique et d’Epidémiologie, Institut Gustave Roussy, Villejuif, France; 4Unité d’Oncologie Thoracique et Cutanée, Centre Hospitalier Universitaire Limoges, Limoges, France Abstract: During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC, with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs per life-year gained (LYG were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY. In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY

  14. Cost analysis of biologic drugs in rheumatoid arthritis first line treatment after methotrexate failure according to patients' body weight.

    Science.gov (United States)

    Román Ivorra, José Andrés; Ivorra, José; Monte-Boquet, Emilio; Canal, Cristina; Oyagüez, Itziar; Gómez-Barrera, Manuel

    2016-01-01

    The objective was to assess the influence of patients' weight in the cost of rheumatoid arthritis treatment with biologic drugs used in first line after non-adequate response to methotrexate. Pharmaceutical and administration costs were calculated in two scenarios: non-optimization and optimization of intravenous (IV) vials. The retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service was used to obtain posology and weight data. The study time horizon was two years. Costs were expressed in 2013 euros. For an average 69kg-weighted patient the lowest cost corresponded to abatacept subcutaneous (SC ABA) (€21,028.09) in the scenario without IV vials optimization and infliximab (IFX) (€20,779.29) with optimization. Considering patients' weight in the scenario without IV vials optimization infliximab (IFX) was the least expensive drug in patients ranged 45-49kg, IV ABA in 50-59kg and SC ABA in patients over 60kg. With IV vials optimization IFX was the least expensive drug in patients under 69kg and SC ABA over 70kg. Assuming comparable effectiveness of biological drugs, patient's weight is a variable to consider, potentials savings could reach €20,000 in two years. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  15. Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia.

    Science.gov (United States)

    Atta, Elias H; Lima, Carlos B L; Dias, Danielle S P; Clé, Diego V; Bonduel, Mariana M; Sciuccati, Gabriela B; Medeiros, Larissa A; Oliveira, Michel M; Salvino, Marco A; Garanito, Marlene P; Blum Fonseca, Patricia B; Saad, Sara Teresinha O; Calado, Rodrigo T; Scheinberg, Phillip

    2017-11-01

    Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10 9 /L (OR 7.64, P  35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10 9 /L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

  16. First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Shu Yong-Qian

    2010-09-01

    Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

  17. Current problems in the first-line treatment of metastatic breast cancer: focus on the role of docetaxel

    Directory of Open Access Journals (Sweden)

    Filippo Montemurro

    2010-09-01

    Full Text Available Metastatic breast cancer is a very heterogeneous disease, both from a clinical and a biological point of view. Despite being still incurable, the expanding therapeutic repertoire has determined a progressive increase in median survival. We describe the clinical course of a 67-year-old woman with a locally advanced, hormone-receptor positive breast cancer with synchronous liver metastases. Single-agent docetaxel at the dose of 100 mg/m2 for 8 cycles determined a pathological complete remission in the breast and a near complete remission of liver metastases. After more than 4 years from diagnosis, the patient is alive and without signs of tumour progression. Based on this clinical case, we discuss management issues like the choice of the initial treatment, the use of monochemotherapy vs polychemotherapy, the worth of surgery of the primary tumour in patients with stage IV disease, and the issue of maintenance endocrine therapy. Furthermore, we reviewed the pivotal role of docetaxel in the management of advanced breast cancer. Whether monochemotherapy or polychemotherapy is felt to be an adequate choice in the clinical practice, docetaxel qualifies as one of the most active and manageable agents. Single agent activity ranging from 20-48% in terms of response rate has been reported in several clinical trials in patients treated in various clinical settings. Docetaxel-based combinations with other cytotoxic agents have become established in the first line treatment both in patients with anthracycline-resistant and anthracycline-sensitive metastatic breast cancer. Finally, docetaxel has been shown to be an optimal companion drug for biologically targeted agents like trastuzumab or bevacizumab, resulting in further treatment options.

  18. [Prospect and Current Situation of Immune Checkpoint Inhibitors 
in First-line Treatment in Advanced Non-small Cell Lung Cancer Patients].

    Science.gov (United States)

    Wang, Haiyang; Yu, Xiaoqing; Fan, Yun

    2017-06-20

    With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients.

  19. Learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer.

    Science.gov (United States)

    Lendínez-Cano, G; Osman García, I; Congregado Ruiz, C B; Conde Sánchez, J M; Medina López, R A

    2018-03-07

    To analyse the learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. We evaluated 32 consecutive patients treated in our department for metastatic renal cancer with tyrosine kinase inhibitors (pazopanib or sunitinib) as first-line treatment between September 2012 and November 2015. We retrospectively analysed this sample. We measured the time to the withdrawal of the first-line treatment, the time to progression and overall survival using Kaplan-Meier curves. The learning curve was analysed with the cumulative sum (CUSUM) methodology. In our series, the median time to the withdrawal of the first-line treatment was 11 months (95% CI 4.9-17.1). The mean time to progression was 30.4 months (95% CI 22.7-38.1), and the mean overall survival was 34.9 months (95% CI 27.8-42). By applying the CUSUM methodology, we obtained a graph for the CUSUM value of the time to withdrawal of the first-line treatment (CUSUM TW), observing 3 well-differentiated phases: phase 1 or initial learning phase (1-15), phase 2 (16-26) in which the management of the drug progressively improved and phase 3 (27-32) of maximum experience or mastery of the management of these drugs. The number of treated patients needed to achieve the proper management of these patients was estimated at 15. Despite the limitations of the sample size and follow-up time, we estimated (in 15 patients) the number needed to reach the necessary experience in the management of these patients with tyrosine kinase inhibitors. We observed no relationship between the time to the withdrawal of the first-line treatment for any cause and progression. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Level of suboptimal adherence to first line antiretroviral treatment & its determinants among HIV positive people in India.

    Science.gov (United States)

    Joshi, Beena; Chauhan, Sanjay; Pasi, Achhelal; Kulkarni, Ragini; Sunil, Nithya; Bachani, Damodar; Mankeshwar, Ranjit

    2014-07-01

    National Anti-retroviral treatment (ART) programme in India was launched in 2004. Since then, there has been no published country representative estimate of suboptimal adherence among people living with HIV (PLHIV) on first line ART in public settings. Hence a multicentric study was undertaken in 15 States of India to assess the level of suboptimal adherence and its determinants among PLHIV. Using a prospective observational study design, 3285 PLHIV were enrolled and followed up to six months across 30 ART centres in India. Adherence was assessed using pill count and self-reported recall method and determinants of suboptimal adherence were explored based on the responses to various issues as perceived by them. Suboptimal adherence was found in 24.5 per cent PLHIV. Determinants of suboptimal adherence were illiteracy (OR--1.341, CI--1.080-1.665), on ART for less than 6 months (OR--1.540, CI--1.280-1.853), male gender (OR for females--0.807, CI--0.662-0.982), tribals (OR--2.246, CI--1.134-4.447), on efavirenz (EFA) regimen (OR--1.479, CI--1.190-1.837), presence of anxiety (OR--1.375, CI--1.117-1.692), non-disclosure of HIV status to family (OR--1.549, CI--1.176-2.039), not motivated for treatment (OR--1.389, CI--1.093-1.756), neglect from friends (OR--1.368, CI--1.069-1.751), frequent change of residence (OR--3.373, CI--2.659-4.278), travel expenses (OR--1.364, CI--1.138-1.649), not meeting the PLHIV volunteer/community care coordinator at the ART center (OR--1.639, CI--1.330-2.019). To enhance identification of PLHIV vulnerable to suboptimal adherence, the existing checklist to identify the barriers to adherence in the National ART Guidelines needs to be updated based on the study findings. Quality of comprehensive adherence support services needs to be improved coupled with vigilant monitoring of adherence measurement.

  1. Level of suboptimal adherence to first line antiretroviral treatment & its determinants among HIV positive people in India

    Directory of Open Access Journals (Sweden)

    Beena Joshi

    2014-01-01

    Full Text Available Background & objectives: National Anti-retroviral treatment (ART programme in India was launched in 2004. Since then, there has been no published country representative estimate of suboptimal adherence among people living with HIV (PLHIV on first line ART in public settings. Hence a multicentric study was undertaken in 15 States of India to assess the level of suboptimal adherence and its determinants among PLHIV. Methods: Using a prospective observational study design, 3285 PLHIV were enrolled and followed up to six months across 30 ART centres in India. Adherence was assessed using pill count and self-reported recall method and determinants of suboptimal adherence were explored based on the responses to various issues as perceived by them. Results: Suboptimal adherence was found in 24.5 per cent PLHIV. Determinants of suboptimal adherence were illiteracy (OR-1.341, CI-1.080-1.665 , on ART for less than 6 months (OR-1.540, CI- 1.280-1.853, male gender (OR for females -0.807, CI- 0.662-0.982, tribals (OR-2.246, CI-1.134-4.447, on efavirenz (EFA regimen (OR- 1.479, CI - 1.190 - 1.837, presence of anxiety (OR- 1.375, CI - 1.117 - 1.692, non-disclosure of HIV status to family (OR- 1.549, CI - 1.176 - 2.039, not motivated for treatment (OR- 1.389, CI - 1.093 - 1.756, neglect from friends (OR-1.368, CI-1.069-1.751, frequent change of residence (OR- 3.373, CI - 2.659 - 4.278, travel expenses (OR- 1.364, CI - 1.138-1.649, not meeting the PLHIV volunteer/community care coordinator at the ART center (OR-1.639, CI-1.330-2.019. Interpretation & conclusions: To enhance identification of PLHIV vulnerable to suboptimal adherence, the existing checklist to identify the barriers to adherence in the National ART Guidelines needs to be updated based on the study findings. Quality of comprehensive adherence support services needs to be improved coupled with vigilant monitoring of adherence measurement.

  2. Qualitative study of patients’ decision-making when accepting second-line treatment after failure of first-line chemotherapy

    Science.gov (United States)

    Roch, Benoît; Roth, Caroline; Mérel, Jean-Pierre

    2018-01-01

    Objective Treatment failures in advanced lung cancer are frequent events affecting patients during or after first-line chemotherapy. International guidelines recommend second-line chemotherapy. However, around one half of patients who experience disease progression enter a systemic second-line therapy. In the herein qualitative study, we investigated patients' thoughts and attitudes determining the decision to undergo a second-line chemotherapy. Methods Thirty-three purposively selected patients who recently accepted second-line or palliative chemotherapy were invited to participate in this survey consisting of semi-structured in-depth interviews. Grounded theory was applied to investigate participants’ perceptions of the context that have surrounded their decision to undergo palliative chemotherapy. Results For most patients, tumor burden and reduced quality of life in relation with lung cancer itself were major drivers of the decision-making process. There was a balance between two different attitudes: making a decision to undergo a new line of chemotherapy or starting a psychological process in order to accept end of life. Choosing between these two attitudes allowed the patient to keep the matter of palliative care at a distance. Even in case of low chance of success, many patients who worried about their life partner's future would accept a new chemotherapy line. Some patients experienced ambivalent thoughts regarding social network, particularly about their family as daily function impairment required an increased need for relative's support. The initial "Worrying about others" thoughts left place to in an increasing self-need of care as those provided by relatives; this phenomenon might increase patients' self- perception of being a burden for others. Confidence previously established with formal caregiver support was another major decision driver: some patients with sustained confidence in their medical staff may have privileged this formal support rather

  3. Nanoparticle albumin-bound paclitaxel combined with cisplatin as the first-line treatment for metastatic esophageal squamous cell carcinoma

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    Shi Y

    2013-05-01

    Full Text Available Yan Shi, Rui Qin, Zhi-Kuan Wang, Guang-Hai DaiDepartment of Multimodality Therapy of Oncology, General Hospital of CPLA, Beijing, People's Republic of ChinaAbstract: Esophageal cancer is a major health hazard in many parts of the world and is often diagnosed late. The objective of this study was to explore the efficacy and safety of nanoparticle albumin-bound paclitaxel (Nab-PTX combined with cisplatin (DDP in patients with metastatic esophageal squamous cell carcinoma (ESCC. Patients with histologically confirmed ESCC were treated with Nab-PTX 250 mg/m2 and DDP 75 mg/m2 intravenously on day 1, every 21 days. Evaluation was performed after every two cycles of therapy and the therapy was continued until disease progression or unacceptable toxicity. From April 2010 to December 2012, 33 patients were enrolled. Ten patients had recurrent and metastatic tumors after surgery and 23 patients were diagnosed with unresectable metastatic disease. Patients received a median of four cycles of therapy (ranging from two to six cycles. Twenty patients achieved partial response and nine patients achieved stable disease; no complete response was observed. The objective response rate was 60.6% and the disease control rate was 87.9%. The median progression-free survival was 6.2 months (95% confidence interval: 4.0 to 8.4 months and the median overall survival was 15.5 months (95% CI: 7.6 to 23.4 months. Only four patients experienced grade 3 adverse events, including vomiting, neutropenia, and sensory neuropathy. The most common adverse events were nausea/vomiting (81.8%, neutropenia (63.6%, leucopenia (48.5%, anemia (24.2% and sensory neuropathy (24.2%. In conclusion, the combination of Nab-PTX and DDP is a highly effective and well-tolerated first-line treatment in metastatic ESCC.Keywords: esophageal squamous cell carcinoma, nanoparticle albumin-bound paclitaxel, chemotherapy, metastasis

  4. Cross-market cost-effectiveness analysis of erlotinib as first-line maintenance treatment for patients with stable non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Vergnenègre A

    2012-01-01

    Full Text Available Alain Vergnenègre1, Joshua A Ray2, Christos Chouaid3, Francesco Grossi4, Helge G Bischoff5, David F Heigener6, Stefan Walzer21Department of Pneumology, Hôpital du Cluzeau, Limoges, France; 2Global Health Economics and Strategic Pricing, F Hoffmann-La Roche Ltd, Basel, Switzerland; 3Respiratory Service, Hôpital Saint Antoine, Paris, France; 4Lung Cancer Unit, National Institute for Cancer Research, Genoa, Italy; 5Thoracic Oncology, Onkologie Thoraxklinik Heidelberg, Heidelberg, Germany; 6Department of Thoracic Oncology, Krankenhaus Großhansdorf, Großhansdorf, GermanyBackground: Platinum-doublet, first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC is limited to 4–6 cycles. An alternative strategy used to prolong the duration of first-line treatment and extend survival in metastatic NSCLC is first-line maintenance therapy. Erlotinib was approved for first-line maintenance in a stable disease population following results from a randomized, controlled Phase III trial comparing erlotinib with best supportive care. We aimed to estimate the incremental cost-effectiveness of erlotinib 150 mg/day versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease.Methods: An economic decision model was developed using patient-level data for progression-free survival and overall survival from the SATURN (SequentiAl Tarceva in UnResectable NSCLC study. An area under the curve model was developed; all patients entered the model in the progression-free survival health state and, after each month, moved to progression or death. A time horizon of 5 years was used. The model was conducted from the perspective of national health care payers in France, Germany, and Italy. Probabilistic sensitivity analyses were performed.Results: Treatment with erlotinib in first-line maintenance resulted in a mean life expectancy of 1.39 years in all countries

  5. Fidaxomicin versus Vancomycin as a First-Line Treatment for Clostridium difficile-Associated Diarrhea in Specific Patient Populations: A Pharmacoeconomic Evaluation.

    Science.gov (United States)

    Reveles, Kelly R; Backo, Jennifer L; Corvino, Frank A; Zivkovic, Marko; Broderick, Kelly C

    2017-12-01

    The reduction in recurrent Clostridium difficile-associated diarrhea (CDAD) with fidaxomicin therapy may reduce hospital readmissions and lead to lower overall CDAD costs. However, studies assessing the cost-effectiveness of fidaxomicin as first-line therapy from the U.S. hospital perspective are lacking. This study evaluated the costs associated with utilizing fidaxomicin or vancomycin as a first-line therapy for CDAD in specific patient populations from a U.S. hospital perspective. A decision-analytic model was developed to estimate total costs (hospitalization and drug costs) associated with using fidaxomicin or vancomycin as first-line therapy for a first episode and up to two recurrences of CDAD in five patient populations: general population, elderly, patients receiving concomitant antibiotics, and patients with renal impairment or cancer. The total cost of CDAD treatment using fidaxomicin first line in the general population was $14,442 per patient versus $14,179 per patient with vancomycin first line. In subgroup analyses, fidaxomicin use resulted in total hospital cost savings of $616 per patient in patients with cancer and $312 in patients with concomitant antibiotic use; vancomycin use was associated with total hospital cost savings of $243 per patient in the elderly and $371 in patients with renal impairment. Fidaxomicin as first-line CDAD therapy is associated with similar total costs as compounded vancomycin oral solution in the general population. In elderly and renally impaired patients, slight increases in hospital cost were observed with fidaxomicin therapy, and in patients with cancer or concomitant antibiotic use, hospital cost savings were observed. © 2017 Pharmacotherapy Publications, Inc.

  6. First-line treatment disruption among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study.

    Science.gov (United States)

    Tang, Derek H; Li, Nanxin; Du, Ella X; Peeples, Miranda; Chu, Lihao; Xie, Jipan; Barghout, Victoria

    2017-12-01

    This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2- metastatic breast cancer (mBC) in the US. Post-menopausal women with HR+/HER2- mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as ≥1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of ≥60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data. A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1-42.2%), liver (8.8-17.3%), and lung (8.6-9.5%). Overall, 37.7% (n = 3,074) of patients receiving endocrine therapy and 86.1% (n = 1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p disruption rates of first-line therapies were sub-optimal among post-menopausal women with HR+/HER2- mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient population.

  7. Cigarette smoking habit does not reduce the benefit from first line trastuzumab-based treatment in advanced breast cancer patients.

    Science.gov (United States)

    Santini, Daniele; Vincenzi, Bruno; Adamo, Vincenzo; Addeo, Raffaele; Fusco, Vittorio; Russo, Antonio; Montemurro, Filippo; Roato, Ilaria; Redana, Stefania; Lanzetta, Gaetano; Satolli, Maria Antonietta; Berruti, Alfredo; Leoni, Valentina; Galluzzo, Sara; Antimi, Mauro; Ferraro, Giuseppa; Rossi, Maura; Del Prete, Salvatore; Valerio, Maria Rosaria; Marra, Monica; Caraglia, Michele; Tonini, Giuseppe

    2011-06-01

    Many ErbB2-positive cancers may show intrinsic resistance, and the frequent development of acquired resistance to ErbB-targeted agents represents a substantial clinical problem. The constitutive NF-κB activation in some HER-2/neu positive breast cancer may represent a potential cause of resistance to trastuzumab therapy. Preclinical data revealed that 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific nitrosamine is able to enhance NF-κB DNA binding activity and theoretically to increase the resistance to trastuzumab. Two hundred and forty-eight women with pathologically confirmed, uni- or bidimensionally measurable, HER-2-positive metastatic breast cancer (MBC) treated with trastuzumab-based therapy as first line combination for metastatic disease were considered eligible. For all included patients data on smoking habit were detectable from medical records. We retrospectively analysed the smoking habits of 248 MBC patients and correlated these habits with activity and efficacy of trastuzumab-based therapy. No statistically significant difference in terms of response rate (RR), time to progression (TTP) and overall survival (OS) was identified between smokers (former plus active smokers) and never smokers. Moreover, no statistically significant difference in terms of RR, TTP and OS was identified either comparing active smokers and former smokers. Moreover, we did not observed any significant statistical difference in terms of TTP and OS between smokers ≥10 cigarettes/day and smoking habit and both activity and efficacy of trastuzumab-based first line therapy in metastatic HER2/neu positive breast cancer patients.

  8. “…still waiting for chloroquine”: the challenge of communicating changes in first-line treatment policy for uncomplicated malaria in a remote Kenyan district

    Science.gov (United States)

    2014-01-01

    Background Widespread parasite resistance to first-line treatment for uncomplicated malaria leads to introduction of new drug interventions. Introducing such interventions is complex and sensitive because of stakeholder interests and public resistance. To enhance take up of such interventions, health policy communication strategies need to deliver accurate and accessible information to empower communities with necessary information and address problems of cultural acceptance of new interventions. Objectives To explore community understanding of policy changes in first-line treatment for uncomplicated malaria in Kenya; to evaluate the potential role of policy communication in influencing responses to changes in first-line treatment policy. Methods Data collection involved qualitative strategies in a remote district in the Kenyan Coast: in-depth interviews (n = 29), focus group discussions (n = 14), informal conversations (n = 11) and patient narratives (n = 8). Constant comparative method was used in the analysis. Being malaria-prone and remotely located, the district offered an ideal area to investigate whether or not and how policy communication about a matter as critical as change of treatment policy reaches vulnerable populations. Results Three years after initial implementation (2009), there was limited knowledge or understanding regarding change of first-line treatment from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in the study district. The print and electronic media used to create awareness about the drug change appeared to have had little impact. Although respondents were aware of the existence of AL, the drug was known neither by name nor as the official first-line treatment. Depending on individuals or groups, AL was largely viewed negatively. The weaknesses in communication strategy surrounding the change to AL included poor choice of communication tools, confusing

  9. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy

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    Bacha Tigist

    2012-08-01

    Full Text Available Abstract Background The emergence of resistance to first line antiretroviral therapy (ART regimen leads to the need for more expensive and less tolerable second line drugs. Hence, it is essential to identify and address factors associated with an increased probability of first line ART regimen failure. The objective of this article is to report on the predictors of first line ART regimen failure, the detection rate of ART regime failure, and the delay in switching to second line ART drugs. Methods A retrospective cohort study was conducted from 2005 to 2011. All HIV infected children under the age of 15 who took first line ART for at least six months at the four major hospitals of Addis Ababa, Ethiopia were included. Data were collected, entered and analyzed using Epi info/ENA version 3.5.1 and SPSS version 16. The Cox proportional-hazard model was used to assess the predictors of first line ART failure. Results Data of 1186 children were analyzed. Five hundred seventy seven (48.8% were males with a mean age of 6.22 (SD = 3.10 years. Of the 167(14.1% children who had treatment failure, 70 (5.9% had only clinical failure, 79 (6.7% had only immunologic failure, and 18 (1.5% had both clinical and immunologic failure. Patients who had height for age in the third percentile or less at initiation of ART were found to have higher probability of ART treatment failure [Adjusted Hazard Ratio (AHR, 3.25 95% CI, 1.00-10.58]. Patients who were less than three years old [AHR, 1.85 95% CI, 1.24-2.76], chronic diarrhea after initiation of antiretroviral treatment [AHR, 3.44 95% CI, 1.37-8.62], ART drug substitution [AHR, 1.70 95% CI, 1.05-2.73] and base line CD4 count below 50 cells/mm3 [AHR, 2.30 95% CI, 1.28-4.14] were also found to be at higher risk of treatment failure. Of all the 167 first line ART failure cases, only 24 (14.4% were switched to second line ART with a mean delay of 24 (SD = 11.67 months. The remaining 143 (85.6% cases were diagnosed

  10. Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site

    DEFF Research Database (Denmark)

    Hainsworth, John D; Daugaard, Gedske; Lesimple, Thierry

    2015-01-01

    : The addition of belinostat to paclitaxel/carboplatin did not improve the PFS of patients with CUP who were receiving first-line therapy, although the patients who received belinostat had a higher investigator-assessed response rate. Future trials in CUP should focus on specific subsets, defined either......BACKGROUND: The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first-line treatment of patients with carcinoma of unknown primary site (CUP). METHODS: In this randomized phase 2 trial......, previously untreated patients with CUP were randomized to receive belinostat plus paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B) repeated every 21 days. Patients were re-evaluated every 2 cycles, and those without disease progression continued treatment for 6 cycles. Patients...

  11. Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.

    Science.gov (United States)

    Zhang, Jingwen; Huang, Yanhong; Wang, Changyi; He, Yuanfang; Zheng, Shukai; Wu, Kusheng

    2017-08-01

    Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.

  12. Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.

    Science.gov (United States)

    Brooks, Katherine; Diero, Lameck; DeLong, Allison; Balamane, Maya; Reitsma, Marissa; Kemboi, Emmanuel; Orido, Millicent; Emonyi, Wilfred; Coetzer, Mia; Hogan, Joseph; Kantor, Rami

    2016-01-01

    Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests. Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for

  13. Design of a randomized trial to evaluate the influence of mobile phone reminders on adherence to first line antiretroviral treatment in South India - the HIVIND study protocol

    Directory of Open Access Journals (Sweden)

    Kumarasamy Nagalingeswaran

    2010-03-01

    Full Text Available Abstract Background Poor adherence to antiretroviral treatment has been a public health challenge associated with the treatment of HIV. Although different adherence-supporting interventions have been reported, their long term feasibility in low income settings remains uncertain. Thus, there is a need to explore sustainable contextual adherence aids in such settings, and to test these using rigorous scientific designs. The current ubiquity of mobile phones in many resource-constrained settings, make it a contextually appropriate and relatively low cost means of supporting adherence. In India, mobile phones have wide usage and acceptability and are potentially feasible tools for enhancing adherence to medications. This paper presents the study protocol for a trial, to evaluate the influence of mobile phone reminders on adherence to first-line antiretroviral treatment in South India. Methods/Design 600 treatment naïve patients eligible for first-line treatment as per the national antiretroviral treatment guidelines will be recruited into the trial at two clinics in South India. Patients will be randomized into control and intervention arms. The control arm will receive the standard of care; the intervention arm will receive the standard of care plus mobile phone reminders. Each reminder will take the form of an automated call and a picture message. Reminders will be delivered once a week, at a time chosen by the patient. Patients will be followed up for 24 months or till the primary outcome i.e. virological failure, is reached, whichever is earlier. Self-reported adherence is a secondary outcome. Analysis is by intention-to-treat. A cost-effectiveness study of the intervention will also be carried out. Discussion Stepping up telecommunications technology in resource-limited healthcare settings is a priority of the World Health Organization. The trial will evaluate if the use of mobile phone reminders can influence adherence to first-line

  14. Design of a randomized trial to evaluate the influence of mobile phone reminders on adherence to first line antiretroviral treatment in South India--the HIVIND study protocol.

    Science.gov (United States)

    De Costa, Ayesha; Shet, Anita; Kumarasamy, Nagalingeswaran; Ashorn, Per; Eriksson, Bo; Bogg, Lennart; Diwan, Vinod K

    2010-03-26

    Poor adherence to antiretroviral treatment has been a public health challenge associated with the treatment of HIV. Although different adherence-supporting interventions have been reported, their long term feasibility in low income settings remains uncertain. Thus, there is a need to explore sustainable contextual adherence aids in such settings, and to test these using rigorous scientific designs. The current ubiquity of mobile phones in many resource-constrained settings, make it a contextually appropriate and relatively low cost means of supporting adherence. In India, mobile phones have wide usage and acceptability and are potentially feasible tools for enhancing adherence to medications. This paper presents the study protocol for a trial, to evaluate the influence of mobile phone reminders on adherence to first-line antiretroviral treatment in South India. 600 treatment naïve patients eligible for first-line treatment as per the national antiretroviral treatment guidelines will be recruited into the trial at two clinics in South India. Patients will be randomized into control and intervention arms. The control arm will receive the standard of care; the intervention arm will receive the standard of care plus mobile phone reminders. Each reminder will take the form of an automated call and a picture message. Reminders will be delivered once a week, at a time chosen by the patient. Patients will be followed up for 24 months or till the primary outcome i.e. virological failure, is reached, whichever is earlier. Self-reported adherence is a secondary outcome. Analysis is by intention-to-treat. A cost-effectiveness study of the intervention will also be carried out. Stepping up telecommunications technology in resource-limited healthcare settings is a priority of the World Health Organization. The trial will evaluate if the use of mobile phone reminders can influence adherence to first-line antiretrovirals in an Indian context.

  15. First-line antiretroviral treatment failure and associated factors in HIV patients at the University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia.

    Science.gov (United States)

    Ayalew, Mohammed Biset; Kumilachew, Dawit; Belay, Assefa; Getu, Samson; Teju, Derso; Endale, Desalegn; Tsegaye, Yemisirach; Wale, Zebiba

    2016-01-01

    Antiretroviral therapy (ART) restores immune function and reduces HIV-related adverse outcomes. But treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. The aim of this study was to determine the prevalence and factors associated with first-line ART failure in HIV patients at the University of Gondar Teaching Hospital. A retrospective study was conducted on 340 adults who had started ART during the period of September 2011 to May 2015. Data regarding patients' sociodemographics, baseline characteristics, and treatment-related information were collected through review of their medical charts. Data were analyzed using SPSS version 21. Descriptive statistics, cross-tabs, and binary and multiple logistic regressions were utilized. Pfailure. The median duration of treatment failure from initiation of treatment was 17.5 months (8-36 months). Poor adherence to treatment and low baseline CD4 cell count were found to be significant predictors of treatment failure. The prevalence of first-line ART failure was 4.1%. Treatment failure was most likely to occur for the patients who had poor drug adherence and those who were delayed to start ART till their CD4 cell count became very low (<100 cells/mm(3)).

  16. Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

    Science.gov (United States)

    Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

    2016-08-01

    Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

  17. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.

    Science.gov (United States)

    Hughes, T P; Saglio, G; Quintás-Cardama, A; Mauro, M J; Kim, D-W; Lipton, J H; Bradley-Garelik, M B; Ukropec, J; Hochhaus, A

    2015-09-01

    BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247.

  18. Cost identification of Nordic FLIRI, Nordic FLOX, XELIRI and XELOX in first-line treatment of advanced colorectal cancer in Sweden -- a clinical practice model approach.

    Science.gov (United States)

    Pettersson, Karin; Carlsson, Göran; Holmberg, Christoffer; Sporrong, Sofia Kälvemark

    2012-09-01

    The role of health-related economy is crucial due to the finite healthcare resources. Intravenous (i.v.) regimes Nordic FLOX and Nordic FLIRI, and the partly oral alternatives XELIRI and XELOX are four commonly used chemotherapies in the first-line treatment of advanced colorectal cancer (CRC) in the Scandinavian countries, all with different costs. To describe and compare costs associated with four commonly used treatments for advanced CRC in clinical routine practice. An additional aim was to evaluate the theoretical cost impact of adverse effects associated with the therapies. The retrospective study was carried out using observations and a clinical quality database of CRC patients treated with Nordic FLOX, Nordic FLIRI, XELIRI and XELOX as first line at an oncology clinic in Gothenburg, Sweden. The treatments are used in parallel in clinical practice. All patients treated from 2003 to 2009 were included. The clinical outcome of the therapies was equivalent; mean treatment time was 5.9-7.7 months. A clinical economic evaluation model was designed. All direct costs associated with the baseline treatment, administration of chemotherapy and drug costs were collected and evaluated. The maximum cost for the four treatments was estimated to be 72 000-75 000 SEK per patient for six months, of this approximately 8000 SEK was linked to treatment of toxicity. During six months the i.v. treatments could include 17 more outpatient visits per patient compared to the oral alternatives. During treatment at the clinic around 20% of the patients were hospitalised (XELOX excluded, because of few included patients). The results indicate that the four regimens are similar in terms of treatment costs. Different costs affect the total cost. The oral alternative makes it possible to treat additional patients with the same labour force resources. Treatment of adverse effects contributes to extensive resource use at the hospital.

  19. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.

    Science.gov (United States)

    Vogel, Charles L; Cobleigh, Melody A; Tripathy, Debu; Gutheil, John C; Harris, Lyndsay N; Fehrenbacher, Louis; Slamon, Dennis J; Murphy, Maureen; Novotny, William F; Burchmore, Michael; Shak, Steven; Stewart, Stanford J; Press, Michael

    2002-02-01

    To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.

  20. A Randomized, Controlled, Multicenter Clinical Trial Comparing Pemetrexed/Cisplatin and Gemcitabine/Cisplatin as First-line Treatment for Advanced Nonsquamous Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan HUANG

    2012-10-01

    Full Text Available Background and objective Platinum-based doublet chemotherapy is still the standard first-line treatment for non-small cell lung cancer (NSCLC. Previous studies have demonstrated that pemetrexed combined with platinum had promising efficacy and safety profile in NSCLC, especially in patients with nonsquamous NSCLC. This trial was conducted to evaluate the efficacy and safety of pemetrexed made in China as first-line treatment. Methods The present study was a randomized, controlled, multicenter clinical trial. Patients were randomly assigned (1:1 to receive cisplatin plus pemetrexed chemotherapy (PC group or gemcitabine plus cisplatin (GC group every 3 weeks. The primary end point was progression free survival (PFS and the secondary end points included 1 year survival rate, objective response rate (ORR, survival without grade 3/4 toxicity (SWT3/4 and safety profile. Results A total of 288 patients from 20 institutions across China were enrolled into the study. Based on the Full Analyses Set (FAS, the PFS was 168 days (5.6 months vs 140 days (4.7 months (P=0.16, one year survival rate was 50.0% vs 54.9% (P=0.47, ORR was 24.4% vs 14.2% (P=0.06 in the PC group and the GC group, respectively; Survival without grade 3/4 toxicity was 11.3 months in GC group vs 8.1 months in PC group (P=0.23. In terms of the safety, side effects were less observed on the PC group (81.95% vs 93.75%, P=0.003. The main side effects included leukopenia, neutropenia, emesis, anemia, thrombopenia. Conclusion The both regimens have similar efficacy as the treatment for advanced nonsquamous NSCLC, but pemetrexed plus cisplatin regimen has better safety profile and seems to have longer PFS, which makes it a new option as the first line setting.

  1. The Impact and Cost-Effectiveness of a Four-Month Regimen for First-Line Treatment of Active Tuberculosis in South Africa.

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    Gwenan M Knight

    Full Text Available A 4-month first-line treatment regimen for tuberculosis disease (TB is expected to have a direct impact on patient outcomes and societal costs, as well as an indirect impact on Mycobacterium tuberculosis transmission. We aimed to estimate this combined impact in a high TB-burden country: South Africa.An individual based M. tb transmission model was fitted to the TB burden of South Africa using a standard TB natural history framework. We measured the impact on TB burden from 2015-2035 of introduction of a non-inferior 4-month regimen replacing the standard 6-month regimen as first-line therapy. Impact was measured with respect to three separate baselines (Guidelines, Policy and Current, reflecting differences in adherence to TB and HIV treatment guidelines. Further scenario analyses considered the variation in treatment-related parameters and resistance levels. Impact was measured in terms of differences in TB burden and Disability Adjusted Life Years (DALYs averted. We also examined the highest cost at which the new regimen would be cost-effective for several willingness-to-pay thresholds.It was estimated that a 4-month regimen would avert less than 1% of the predicted 6 million person years with TB disease in South Africa between 2015 and 2035. A similarly small impact was seen on deaths and DALYs averted. Despite this small impact, with the health systems and patient cost savings from regimen shortening, the 4-month regimen could be cost-effective at $436 [NA, 5983] (mean [range] per month at a willingness-to-pay threshold of one GDP per capita ($6,618.The introduction of a non-inferior 4-month first-line TB regimen into South Africa would have little impact on the TB burden. However, under several scenarios, it is likely that the averted societal costs would make such a regimen cost-effective in South Africa.

  2. Efficacy and Safety of the Triple Therapy Containing Ilaprazole, Levofloxacin, and Amoxicillin as First-Line Treatment in Helicobacter pylori Infections

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    Hyo Jun Ahn

    2017-01-01

    Full Text Available Background and Aims. To establish the efficacy and safety of ilaprazole, levofloxacin, and amoxicillin as a first-line eradication treatment for Helicobacter pylori. Methods. Patients with gastric ulcer, duodenal ulcer, or gastritis, as detected by esophagogastroduodenoscopy with confirmed H. pylori infection between September 2014 and November 2015, were enrolled in the study. All participants received ilaprazole (10 mg bid, levofloxacin (500 mg bid, and amoxicillin (1000 mg bid for 10 days. H. pylori eradication was confirmed by a 13C-urea breath test at 6–8 weeks after the end of treatment. Results. Of 84 patients included in the analysis, the eradication rate was 88.8% in the per protocol group (n=80. Demographic factors such as age, gender, body mass index (BMI, alcohol, smoking, hypertension, diabetes mellitus, and peptic ulcer did not affect the eradication rate. However, multivariate analysis showed that overweight patients and patients with cerebrovascular accident (CVA had a significantly lower eradication rate than patients with normal BMI and without CVA. Laboratory test results did not change significantly after treatment. A total of six (7.5% patients developed eight adverse reactions. Conclusions. A 10-day triple therapy containing ilaprazole, levofloxacin, and amoxicillin is a safe alternative first-line eradication treatment for H. pylori.

  3. The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

    Science.gov (United States)

    Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

    2010-01-01

    Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

  4. Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, L H; Sindrup, S H; Christiansen, I

    2017-01-01

    BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment...... treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function...... tests. RESULTS: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG...

  5. Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

    Directory of Open Access Journals (Sweden)

    Mezei Z

    2012-10-01

    Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

  6. Hydroxyurea as a first-line treatment of extramedullary hematopoiesis in patients with beta thalassemia: Four case reports.

    Science.gov (United States)

    Karimi, Mehran; Cohan, Nader; Pishdad, Parisa

    2015-01-01

    Extramedullary hematopoiesis (EMH) is evidenced by erythropoietic masses, which occurs as a compensatory mechanism to overcome hypoxia during chronic anemia. EMH masses in spinal cord could lead to cord compression and neurological symptoms. Besides transfusion, radiotherapy, and surgery, hydroxyurea (HU) is also a treatment strategy in EMH. We described four cases of beta thalassemia with EMH who were treated with HU as a monotherapy. INTERVENTION (AND TECHNIQUE): HU therapy was done in all patients without any transfusion during therapy. HU is a good treatment option for patients with EMH and it could be a substitute for radiotherapy and invasive surgery or regular blood transfusion.

  7. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma

    DEFF Research Database (Denmark)

    Judson, Ian; Verweij, Jaap; Gelderblom, Hans

    2014-01-01

    BACKGROUND: Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used...

  8. Cumulative clinical experience from a decade of use: imatinib as first-line treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Baran Y

    2012-11-01

    Full Text Available Yusuf Baran,1 Guray Saydam21Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey; 2Department of Hematology, School of Medicine, Ege University, Izmir, TurkeyAbstract: Chronic myeloid leukemia (CML is a malignant disease that originates in the bone marrow and is designated by the presence of the Philadelphia (Ph+ chromosome, a translocation between chromosomes 9 and 22. Targeted therapy against CML commenced with the development of small-molecule tyrosine kinase inhibitors (TKIs exerting their effect against the oncogenic breakpoint cluster region (BCR-ABL fusion protein. Imatinib emerged as the first successful example of a TKI used for the treatment of chronic-phase CML patients and resulted in significant improvements in response rate and overall survival compared with previous treatments. However, a significant portion of patients failed to respond to the therapy and developed resistance against imatinib. Second-generation TKIs nilotinib and dasatinib were to have higher efficiency in clinical trials in imatinib- resistant or intolerant CML patients compared with imatinib. Identification of novel strategies such as dose escalation, drug combination therapy, and use of novel BCR-ABL inhibitors may eventually overcome resistance against BCR-ABL TKIs. This article reviews the history of CML, including the treatment strategies used prediscovery of TKIs and the preclinical and clinical data obtained after the use of imatinib, and the second-generation TKIs developed for the treatment of CML.Keywords: drug resistance, tyrosine kinase inhibitors, chronic myeloid leukemia, imatinib, BCR/ABL

  9. Patient preferences for first-line oral treatment for mild-to-moderate ulcerative colitis: a discrete-choice experiment.

    Science.gov (United States)

    Hodgkins, Paul; Swinburn, Paul; Solomon, Dory; Yen, Linnette; Dewilde, Sarah; Lloyd, Andrew

    2012-01-01

    Patients with ulcerative colitis (UC) frequently require long-term therapy to prevent relapse. Treatments such as 5-aminosalicylic acid (5-ASA [mesalazine]) are efficacious and well tolerated, but adherence to treatment is often poor. This discrete-choice experiment (DCE) was conducted to estimate differences in patient preferences for 5-ASA treatment in mild-to-moderate UC based on levels of self-reported adherence. Inclusion of patients residing in the US, UK, Germany, and Canada allowed for assessment of possible cultural differences in patient preferences. DCE attributes were determined through literature review, clinician consultation, and patient interviews. Six treatment attributes were identified: ease of swallowing, time of day, quantity, extent of flare resolution, likelihood of flare occurrence, and cost. A total of 400 patients in four countries completed the DCE and adherence (Modified Morisky Scale) surveys. Data were analyzed using generalized estimating equations to estimate patient preference and willingness to pay (WTP) by levels of self-reported adherence and country of residence. All attributes had expected polarity and were significant predictors of patient preference. Self-reported 'good' versus 'poor' adherers significantly preferred symptom control (p = 0.0108) and mucosal healing (p = 0.0190) attributes. All patients stated preference for symptom control/mucosal healing and flare risk attributes; the latter attribute was significantly preferred across all countries. Country differences in patient preference for convenience versus clinical attributes were found. Overall, patients were willing to pay £29.24 ($US46.27) per month for symptom control and mucosal healing, and an additional £78.81 ($US124.70) per month for reduction in flare risk to 10% per year (WTP costs were equalized between each country using the published 2008 purchasing power parity). Those with flares in the past year significantly preferred avoiding future

  10. Adoption of new HIV treatment guidelines and drug substitutions within first-line as a measure of quality of care in rural Lesotho: health centers and hospitals compared.

    Science.gov (United States)

    Labhardt, Niklaus D; Sello, Motlalepula; Lejone, Thabo; Ehmer, Jochen; Mokhantso, Mohlaba; Lynen, Lutgarde; Pfeiffer, Karolin

    2012-10-01

    In 2007, Lesotho launched new national antiretroviral treatment (ART) guidelines, prioritising tenofovir and zidovudine over stavudine as a backbone together with lamivudine. We compared the rate of adoption of these new guidelines and substitution of first-line drugs by health centers (HC) and hospitals in two catchment areas in rural Lesotho. Retrospective cohort analysis. Patients aged ≥16 years were stratified into a HC- and a hospital-group. Type of backbone at ART-initiation (i), substitutions within first line (ii) and type of backbone among patients retained by December 2010 (iii). A multiple logistic regression model including HC vs. hospital, patient characteristics (sex, age, WHO-stage, baseline CD4-count, concurrent pregnancy, concurrent tuberculosis treatment) and year of ART-start, was used. Of 3936 adult patients initiated on ART between 2007 and 2010, 1971 started at hospitals and 1965 at HCs. Hospitals were more likely to follow the new guidelines as measured by prescription of backbones without stavudine (Odds-ratio 1.55; 95%CI: 1.32-1.81) and had a higher rate of drug substitutions while on first-line ART (2.39; 1.83-3.13). By December 2010, patients followed at health centres were more likely to still receive stavudine (2.28; 1.83-2.84). Health centers took longer to adopt the new guidelines and substituted drugs less frequently. Decentralised ART-programmes need close support, supervision and mentoring to absorb new guidelines and to adhere to them. © 2012 Blackwell Publishing Ltd.

  11. Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study.

    Science.gov (United States)

    Li, Wenhua; Zhao, Xiaoying; Wang, Huijie; Liu, Xin; Zhao, Xinmin; Huang, Mingzhu; Qiu, Lixin; Zhang, Wen; Chen, Zhiyu; Guo, Weijian; Li, Jin; Zhu, Xiaodong

    2017-06-06

    Maintenance therapy proves to be effective in advanced lung and breast cancer after initial chemotherapy. The purpose of this phase II study was to evaluate the efficacy and safety of Uracil and Tegafur (UFT) maintenance in metastatic gastric cancer patients following the first-line fluorouracil-based chemotherapy. Metastatic gastric cancer patients with stable disease or a better response after the completion of first-line chemotherapy were randomized to oral UFT (360mg/m2 × 2 weeks) every 3 weeks until disease progression/intolerable toxicity or to observation (OBS). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS) and safety. The trial was closed after the interim analysis of the 58 enrolled (120 planned) patients. Median PFS was not improved in the UFT group compared with the OBS group (3.2 months versus 3.6 months, P = 0.752), as well as the median OS (14.2 months for both, P = 0.983). However, subgroup analysis showed that low baseline hemoglobin (maintenance therapy (P = 0.032), while the normal hemoglobin patients benefit from the UFT treatment (P = 0.008). Grade 3 to 4 toxicities in the UFT group were anemia (3.4%), thrombocytopenia (3.4%) and diarrhea (6.9%). This trial did not show superiority of UFT maintenance in non-selected patients responding to fluorouracil-based first-line chemotherapy. The normal hemoglobin level at baseline is a predictive biomarker for favorable patient subsets from the maintenance treatment.

  12. Retrospective Evaluation of Hairy Cell Leukemia Patients Treated with Three Different First-Line Treatment Modalities in the Last Two Decades: A Single-Center Experience

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    Şeniz Öngören

    2017-12-01

    Full Text Available Objective: In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL cases. Materials and Methods: Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA was administered in 31 cases, 19 patients received interferon-alpha (INF-α, splenectomy was performed in 16 cases, and rituximab was used in one. Results: Although the highest overall response rate (ORR was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem. Conclusion: Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.

  13. A pilot study of gestational diabetes mellitus not controlled by diet alone: First-line medical treatment with myoinositol may limit the need for insulin.

    Science.gov (United States)

    Lubin, V; Shojai, R; Darmon, P; Cosson, E

    2016-06-01

    This study assessed whether myoinositol might be a first-line medical treatment for gestational diabetes mellitus (GDM). For 12 months, women with GDM not controlled by diet (n=32) were prospectively treated with myoinositol 1200mg and folic acid 400μg/day, while consecutive women (n=28) with insulin-requiring GDM treated during the previous year at our centre constituted the control group. Baseline characteristics and care were similar in both groups. Insulin was required in eight women (25%) in the myoinositol group who, compared with the 24 who did not need insulin, were older (37±5 vs. 32±5 years, respectively; P=0.018) and had a larger percentage of high self-monitored glucose values (45±8% vs. 32±14%; P<0.0001) during the week prior to the introduction of myoinositol treatment. All of the women had similar pregnancy outcomes regardless of their GDM management, although less labour induction was required in the myoinositol group (OR: 0.22 [0.07-0.65]), which had no side effects. This pilot study suggests that myoinositol may be a safe first-line medical treatment for uncontrolled GDM. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. The background and rationale for a new fixed-dose combination for first-line treatment of tuberculosis in children.

    Science.gov (United States)

    Graham, S M; Grzemska, M; Gie, R P

    2015-12-01

    In 2010, the World Health Organization revised the recommendations for the treatment of tuberculosis (TB) in children. The major revision was to increase isoniazid, rifampicin and pyrazinamide dosages according to body weight in children. The recommendations for higher dosages are based on consistent evidence from 1) pharmacokinetic studies suggesting that young children require higher dosages than adolescents and adults to achieve desired serum concentrations; and 2) observational studies reporting that the higher dosages would not be associated with increased risk of toxicity in children. However, national tuberculosis programmes faced unforeseen challenges in implementing the revised recommendations. The main difficulty was to adapt the revised dosages for the treatment of children with drug-susceptible TB using available fixed-dose combinations (FDCs). A more suitable FDC for the intensive and continuation phases of treatment has now been developed for planned implementation in 2015. This paper explains the background and rationale for the development of a new FDC tablet for children with drug-susceptible TB.

  15. Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

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    Catriona Elizabeth Mactier

    2012-10-01

    Full Text Available Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

  16. High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Rasmussen, Mads Heilskov; Jensen, Niels; Tarpgaard, Line Schmidt

    2013-01-01

    The backbone of current cytotoxic treatment of metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine together with either oxaliplatin (XELOX/FOLFOX) or irinotecan (XELIRI/FOLFIRI). With an overall objective response rate of approximately 50% for either treatment combination, a major...... analyses showed that miR-625-3p was not dysregulated between normal and cancer samples, nor was its expression associated with recurrence of stage II or III disease, indicating that miR-625-3p solely is a response marker. Finally, we also found that these miRNAs were up-regulated in oxaliplatin resistant...... unsolved problem is that no predictors of response to these treatments are available. To address this issue, we profiled 742 microRNAs in laser-capture microdissected cancer cells from responding and non-responding patients receiving XELOX/FOLFOX as first-line treatment for mCRC, and identified, among...

  17. More than 5000 patients with metastatic melanoma in Europe per year do not have access to recommended first-line innovative treatments

    DEFF Research Database (Denmark)

    Kandolf Sekulovic, L.; Peris, Ketty; Hauschild, A.

    2017-01-01

    Background Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access...... to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF...... treated with innovative medicines and a number of reimbursed medicines. Conclusions Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma...

  18. GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    T. E. Shmidt

    2016-01-01

    Full Text Available Multiple sclerosis (MS is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs. To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

  19. Sustainability of first-line antiretroviral regimens: findings from a large HIV treatment program in western Kenya.

    Science.gov (United States)

    Braitstein, Paula; Ayuo, Paul; Mwangi, Ann; Wools-Kaloustian, Kara; Musick, Beverly; Siika, Abraham; Kimaiyo, Sylvester

    2010-02-01

    To describe first change or discontinuation in combination antiretroviral treatment (cART) among previously treatment naive, HIV-infected adults in a resource-constrained setting. The United States Agency for International Development-Academic Model Providing Access to Healthcare Partnership has enrolled >90,000 HIV-infected patients at 18 clinics throughout western Kenya. Patients in this analysis were aged > or =18 years, previously antiretroviral treatment naive, and initiated to cART between January 2006 and November 2007, with at least 1 follow-up visit. A treatment change or discontinuation was defined as change of regimen including single drug substitutions or a complete halting of cART. There were 14,162 patients eligible for analysis and 10,313 person-years of follow-up, of whom 1376 changed or stopped their cART. Among these, 859 (62%) changed their regimen (including 514 patients who had a single drug substitution) and 517 (38%) completely discontinued cART. The overall incidence rate (IR) of cART changes or stops per 100 person-years was 13.3 [95% confidence interval (CI): 12.7-14.1]. The incidence was much higher in the first year of post-cART initiation (IR: 25.0, 95% CI: 23.6-26.3) compared with the second year (IR: 2.4, 95% CI: 2.0-2.8). The most commonly cited reason was toxicity (46%). In multivariate regression, individuals were more likely to discontinue cART if they were World Health Organization stage III/IV [adjusted hazard ratio (AHR): 1.37, 95% CI: 1.11-1.69] or were receiving a zidovudine-containing regimen (AHR: 4.44, 95% CI: 3.35-5.88). Individuals were more likely to change their regimen if they were aged > or =38 years (AHR: 1.44, 95% CI: 1.23-1.69), had to travel more than 1 hour to clinic (AHR: 1.34, 95% CI: 1.15-1.57), had a CD4 at cART initiation < or =111 cells/mm3 (AHR: 1.51, 95% CI: 1.29-1.77), or had been receiving a zidovudine-containing regimen (AHR: 3.73, 95% CI: 2.81-4.95). Those attending urban clinics and those receiving

  20. Prevalence of metabolic syndrome in HIV-infected patients naive to antiretroviral therapy or receiving a first-line treatment.

    Science.gov (United States)

    Calza, Leonardo; Colangeli, Vincenzo; Magistrelli, Eleonora; Rossi, Nicolo'; Rosselli Del Turco, Elena; Bussini, Linda; Borderi, Marco; Viale, Pierluigi

    2017-05-01

    The combination antiretroviral therapy (cART) has dramatically improved the life expectancy of patients with HIV infection, but may lead to several long-term metabolic abnormalities. However, data about the frequency of metabolic syndrome (MS) in HIV-infected people vary considerably across different observational studies. The prevalence of MS among HIV-infected patients was evaluated by a cross-sectional study conducted among subjects naive to cART or receiving the first antiretroviral regimen and referring to our Clinics from January 2015 to December 2015. The diagnosis of MS was made based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. The study recruited 586 patients: 98 naive to cART and 488 under the first antiretroviral treatment. The prevalence of MS, according to NCEP-ATP III criteria, was significantly higher among treated patients than among naive ones (20.9% vs. 7.1%; p = 0.014). The most frequently reported components of MS among treated patients were high triglycerides (44.3%), low high-density lipoprotein cholesterol (41.1%), and hypertension (19.7%). On multivariate analysis, long duration of HIV infection, low nadir of CD4 lymphocytes, high body mass index, current use of one protease inhibitor, and long duration of cART were significantly associated with a higher risk of MS, while current use of one integrase inhibitor was significantly associated with a lower risk of MS. The non-negligible prevalence of MS among HIV-infected patients under cART requires a careful and periodic monitoring of its components, with particular attention to dyslipidemia and hypertension.

  1. The effectiveness of RECIST on survival in patients with NSCLC receiving chemotherapy with or without target agents as first-line treatment.

    Science.gov (United States)

    Zhou, Ting; Zheng, Lie; Hu, Zhihuang; Zhang, Yang; Fang, Wenfeng; Zhao, Yuanyuan; Ge, Jieying; Zhao, Hongyun; Zhang, Li

    2015-01-08

    We analyzed the correlation between survival and antitumor effect evaluated by RECIST in advanced NSCLC patients with chemotherapy plus target therapy or not as first-line treatment, to examine the applicability of RECIST in this population. The patients were screened from 4 clinical trials (12621, 12006, FASTACT-I, and FASTACT-II), and those who received chemotherapy plus target therapy or chemotherapy alone were eligible. Among the 59 enrolled patients, 29 received combination therapy, while the other 30 received chemotherapy only. In the combination therapy group, patients with PR or SD had longer overall survival (OS) than those with PD (P chemotherapy alone group, compared with PD patients, either PR or SD group had no significant overall survival benefit (P = 0.690 and P = 0.528, respectively). In summary, for advanced NSCLC patients receiving chemotherapy plus target therapy as first-line treatment and evaluated by RECIST criteria, SD has the same overall survival benefit as PR, suggesting that antitumor effective evaluation by RECIST criteria cannot be translated to overall survival benefit especially for this kind of patients. Therefore, developing a more comprehensive evaluation method to perfect RECIST criteria is thus warranted for patients received target therapy in NSCLC.

  2. Effect of first line cancer treatment on the ovarian reserve and follicular density in girls under the age of 18 years

    DEFF Research Database (Denmark)

    El Issaoui, Meryam; Giorgione, Veronica; Mamsen, Linn S

    2016-01-01

    the age of 18 years who underwent OTC before (group 1: 31 patients) and after (group 2: 32 patients) their initial cancer treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Follicular densities (follicles/mm(3)) measured from an ovarian cortical biopsy before OTC. The ovarian volume (mL) of entire...... to have little effect on the follicle pool. This information will improve counseling of young female cancer patients in deciding whether to undergo fertility preservation treatment.......OBJECTIVE: To study the impact of first-line antineoplastic treatment on ovarian reserve in young girls returning for ovarian tissue cryopreservation (OTC) in connection with a relapse. DESIGN: Retrospective case-control study. SETTING: University hospitals. PATIENT(S): Sixty-three girls under...

  3. Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation

    DEFF Research Database (Denmark)

    Tram Henriksen, Louise; Gottschalk Højfeldt, Sofie; Schmiegelow, Kjeld

    2017-01-01

    BACKGROUND: As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment. METHODS: The aim of this study was to evaluate the pharmacokinetics...... of prolonged upfront biweekly PEG-asparaginase (where PEG is polyethylene glycol) treatment by measuring serum l-asparaginase activity and formation of anti-PEG-asparaginase antibodies. A total of 97 evaluable patients (1-17 years), diagnosed with ALL, and treated according to the NOPHO ALL2008 protocol (where...... NOPHO is Nordic Society of Paediatric Haematology and Oncology) were included. In the NOPHO ALL2008 protocol, patients are randomized to 8 or 15 doses of intramuscular PEG-asparaginase (Oncaspar(®) ) 1,000 IU/m²/dose, at 2-week or 6-week intervals with a total of 30-week treatment (Clinical trials...

  4. Vaccines against drugs of abuse: a viable treatment option?

    Science.gov (United States)

    Kantak, Kathleen M

    2003-01-01

    Drug addiction is a chronically relapsing brain disorder. There is an urgent need for new treatment options for this disease because the relapse rate among drug abusers seeking treatment is quite high. During the past decade, many groups have explored the feasibility of using vaccines directed against drugs of abuse as a means of eliminating illicit drug use as well as drug overdose and neurotoxicity. Vaccines work by inducing drug-specific antibodies in the bloodstream that bind to the drug of abuse and prevent its entry into the brain. The majority of work in this area has been conducted with vaccines and antibodies directed against cocaine and nicotine. On the basis of preclinical work, vaccines for cocaine and nicotine are now in clinical trials because they can offer long-term protection with minimal treatment compliance. In addition, vaccines and antibodies for phencyclidine, methamphetamine and heroin abuse are currently under development. An underlying theme in this research is the need for high concentrations of circulating drug-specific antibodies to reduce drug-seeking and drug-taking behaviour when the drug is repeatedly available, especially in high doses. Although vaccines against drugs of abuse may become a viable treatment option, there are several drawbacks that need to be considered. These include: a lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice;a lack of an effect on drug craving that predisposes an addict to relapse; and tremendous individual variability in antibody formation. Forced or coerced vaccination is not likely to work from a scientific perspective, and also carries serious legal and ethical concerns. All things considered, vaccination against a drug of abuse is likely to work best with individuals who are highly motivated to quit using drugs altogether and as part of a comprehensive treatment programme. As such, the medical treatment of drug abuse will not be radically

  5. Tandem autotransplant as first-line consolidative treatment in poor-risk aggressive lymphoma: a pilot study of 36 patients.

    Science.gov (United States)

    Haioun, C; Mounier, N; Quesnel, B; Morel, P; Rieux, C; Beaujean, F; Marolleau, J P; Belhadj, K; Simon, D; Gaulard, P H; Lepage, E; Gisselbrecht, C H; Reyes, F

    2001-12-01

    In the previous LNH87-2 study, consolidative high-dose therapy followed by stem cell transplantation (HDT) improved disease-free survival, as well as survival for patients (pts) presenting with two or three factors of the age-adjusted international prognostic index (Aa-IPI) in first complete remission (CR). In order to improve further the outcome of such patients, we conducted a pilot study of consolidative tandem autotranplant. Thirty-six patients (pts) under 60 years of age with two or three factors of the Aa-IPI were enrolled. Their main characteristics were: diffuse large B-cell lymphoma (83%), Aa-IPI three factors (50%), and marrow involved (36)%. The procedure consisted of 1) induction with four cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) 2) in responding pts, peripheral blood stem cell (PBSC) collection after the fourth cycle of ACVBP (11 pts) or after an additional mobilization regimen (Cyclophosphamide-VP16) (17 pts) 3) a first HDT (mitoxantrone, cyclophosphamide, VP16 and carmustine) followed by PBSC infusion 4) a second HDT (busulfan, carboplatin and melphalan) followed by PBSC infusion. Among the 29 patients responding to induction, 28 received the first HDTand 24 the second. The rates of three-year-event free survival and survival are 47% (95% confidence interval (95% CI: 31%-63%) and 50% (95% CI: 37%-69%), respectively. Eighteen patients remained free of evolutive disease and 18 patients have died, 15 from disease progression and three from treatment-related toxicity after tandem transplant (two veno-occlusive disease and one cerebral toxoplasmosis). We conclude that tandem transplant did not improve the results of the LNH87-2 study in which patients received a single consolidative HDT.

  6. Managing first-line failure.

    Science.gov (United States)

    Cooper, David A

    2014-01-01

    WHO standard of care for failure of a first regimen, usually 2N(t)RTI's and an NNRTI, consists of a ritonavir-boosted protease inhibitor with a change in N(t)RTI's. Until recently, there was no evidence to support these recommendations which were based on expert opinion. Two large randomized clinical trials, SECOND LINE and EARNEST both showed excellent response rates (>80%) for the WHO standard of care and indicated that a novel regimen of a boosted protease inhibitor with an integrase inhibitor had equal efficacy with no difference in toxicity. In EARNEST, a third arm consisting of induction with the combined protease and integrase inhibitor followed by protease inhibitor monotherapy maintenance was inferior and led to substantial (20%) protease inhibitor resistance. These studies confirm the validity of the current recommendations of WHO and point to a novel public health approach of using two new classes for second line when standard first-line therapy has failed, which avoids resistance genotyping. Notwithstanding, adherence must be stressed in those failing first-line treatments. Protease inhibitor monotherapy is not suitable for a public health approach in low- and middle-income countries.

  7. Flipped script for gefitinib: A reapproved tyrosine kinase inhibitor for first-line treatment of epidermal growth factor receptor mutation positive metastatic nonsmall cell lung cancer.

    Science.gov (United States)

    Bogdanowicz, Brian S; Hoch, Matthew A; Hartranft, Megan E

    2017-04-01

    Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917). Both studies were recently referenced by the United States Food & Drug Administration to reapprove gefitinib for the first-line treatment of advanced nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 substitution. Diarrhea, acneiform rash, and interstitial lung disease are known side effects of gefitinib. Conclusion Use of gefitinib for the first-line therapy of metastatic nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions (residues 747-750) or exon 21 substitution mutation (L858R) is well-documented and supported.

  8. Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies

    Directory of Open Access Journals (Sweden)

    Felger Ingrid

    2005-11-01

    Full Text Available Abstract Background Systematic surveillance for resistant malaria shows high level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP across eastern and southern parts of Africa. This study assessed in vivo SP efficacy after two years of use as an interim first-line drug in Tanzania, and determined the rates of treatment failures obtained after 14 and 28 days of follow-up. Methods The study was conducted in the Ipinda, Mlimba and Mkuranga health facilities in Tanzania. Children aged 6–59 months presenting with raised temperature associated exclusively with P. falciparum (1,000–100,000 parasites per μl were treated with standard dose of SP. Treatment responses were classified according to the World Health Organization (WHO definition as Adequate Clinical and Parasitological Response (ACPR, Early Treatment Failure (ETF, Late Clinical Failure (LCF and Late Parasitological Failure (LPF on day 14 and day 28. Results Overall 196 (85.2% of 230 patients had ACPR on day 14 but only 116 (50.9% on day 28 (57.7% after excluding new infections by parasite genotyping. Altogether 21 (9.1% and 13 (5.7% of the 230 patients assessed up to day 14 and 39 (17.1% and 55 (24.1% of the 228 followed up to day 28 had clinical and parasitological failure, respectively. Conclusion These findings indicate that SP has low therapeutic value in Tanzania. The recommendation of changing first line treatment to artemether + lumefantrine combination therapy from early next year is, therefore, highly justified. These findings further stress that, for long half-life drugs such as SP, establishment of cut-off points for policy change in high transmission areas should consider both clinical and parasitological responses beyond day 14.

  9. Balancing risk and benefit for first-line treatment of metastatic colorectal cancer: a graphic communication tool for patients and physicians.

    Science.gov (United States)

    Sanatani, Michael S; Vincent, Mark D

    2007-01-01

    Advances in the treatment of metastatic colorectal cancer have improved overall survival (OS); however, this might come at the cost of increased toxicity. Health-related quality of life, a significant concern closely related to toxicity and important when discussing palliative therapy, is infrequently assessed and reported in older clinical trials. As the number of tested regimens increases, the question arises on how to best present palliative treatment options. We present a simple way to compare treatment options in terms of potential risks and benefits. The literature was surveyed for reports of first-line systemic chemotherapies for metastatic colorectal cancer. The largest recent reports with detailed toxicity data were selected as representative for a regimen. Toxicity sum of a regimen was calculated as percent occurrences in the study cohort of severe adverse effects: diarrhea, mucositis, neurocutaneous conditions (excluding alopecia), vomiting, and febrile neutropenia. Limitations of toxicity reporting precluded inclusion of other or milder adverse events. Benefits (OS and progression-free survival [PFS]) were plotted graphically as benefit versus toxicity sum. Thirty-four regimens were found. Overall survival, PFS, and toxicity sum ranged from 8.9-24.7 months, 4.9-9.2 months, and 12-70 months, respectively. Weaknesses of our study include omission of some specific toxicities and of symptom control benefit, as well as heterogeneity of trial design and study populations. Furthermore, more recent OS data might reflect the availability of more lines of therapy rather than the effect of the first-line regimen, as comparison with PFS outcomes show. Our comparative tool helps physicians discuss the large number of available options with a patient in order to arrive at the treatment plan most appropriate to the individual and improve informed consent and disclosure, while highlighting limitations in available evidence.

  10. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial.

    Science.gov (United States)

    D'Angelo, Sandra P; Russell, Jeffery; Lebbé, Céleste; Chmielowski, Bartosz; Gambichler, Thilo; Grob, Jean-Jacques; Kiecker, Felix; Rabinowits, Guilherme; Terheyden, Patrick; Zwiener, Isabella; Bajars, Marcis; Hennessy, Meliessa; Kaufman, Howard L

    2018-03-22

    Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti-programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC. JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. As of March 24, 2017, 39 patients were enrolled (30 men and 9 women; median age, 75 years [range, 47-88 years]), with a median follow-up of 5.1 months (range, 0.3-11.3 months). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up; the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing at the time of analysis. In responding patients, the estimated proportion with duration of response of at

  11. Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

    Directory of Open Access Journals (Sweden)

    Giroux Leprieur E

    2016-06-01

    Full Text Available Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Department, APHP – Tenon Hospital, Paris, France; 4Sorbonne University, GRC 04, UPMC Univ Paris 06, France Abstract: Around 4% of advanced non-small-cell lung cancers (NSCLCs have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy depends on the phenotype of the progression, the

  12. First line treatment response in patients with transmitted HIV drug resistance and well defined time point of HIV infection: updated results from the German HIV-1 seroconverter study.

    Directory of Open Access Journals (Sweden)

    Fabia Zu Knyphausen

    Full Text Available BACKGROUND: Transmission of drug-resistant HIV-1 (TDR can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed. METHODS: Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined. RESULTS: Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667 in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0% and decreased significantly over time (OR = 0.92, CI = 0.87-0.98, p = 0.01. Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92-1.09, p = 0.96 and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17 remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41. CONCLUSION: Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were

  13. Cost-effectiveness of adding cetuximab to platinum-based chemotherapy for first-line treatment of recurrent or metastatic head and neck cancer.

    Directory of Open Access Journals (Sweden)

    Malek B Hannouf

    Full Text Available To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC from the perspective of the Canadian public healthcare system.We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%.In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of $36,000 per person, resulting in an incremental cost effectiveness ratio (ICER of $386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab.The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy.

  14. Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux.

    Science.gov (United States)

    Puri, Prem; Kutasy, Balazs; Colhoun, Eric; Hunziker, Manuela

    2012-10-01

    In recent years the endoscopic injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis and the surgical management of vesicoureteral reflux. We determined the safety and effectiveness of the endoscopic injection of dextranomer/hyaluronic acid as first line treatment for high grade vesicoureteral reflux. Between 2001 and 2010, 1,551 children (496 male, 1,055 female, median age 1.6 years) underwent endoscopic correction of intermediate and high grade vesicoureteral reflux using dextranomer/hyaluronic acid soon after the diagnosis of vesicoureteral reflux on initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 761 children and bilateral in 790. Renal scarring was detected in 369 (26.7%) of the 1,384 patients who underwent dimercapto-succinic acid imaging. Reflux grade in the 2,341 ureters was II in 98 (4.2%), III in 1,340 (57.3%), IV in 818 (34.9%) and V in 85 (3.6%). Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure, and renal ultrasound was performed annually thereafter. Patients were followed for 3 months to 10 years (median 5.6 years). Vesicoureteral reflux resolved after the first, second and third endoscopic injection of dextranomer/hyaluronic acid in 2,039 (87.1%), 264 (11.3%) and 38 (1.6%) ureters, respectively. Febrile urinary tract infections developed during followup in 69 (4.6%) patients. None of the patients in the series needed reimplantation of ureters or experienced any significant complications. Our results confirm the safety and efficacy of the endoscopic injection of dextranomer/hyaluronic acid in the eradication of high grade vesicoureteral reflux. We recommend this 15-minute outpatient procedure as the first line of treatment for high grade vesicoureteral reflux. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Ming Li

    Full Text Available To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC.A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS, progression-free survival (PFS, response rate (RR, and different types of toxicity. Hazard ratios (HRs, odds ratios (ORs and their 95% confidence intervals (CIs were pooled using RevMan software.Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC improved survival compared with other platinum-based regimens (PBR in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04, especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02. No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95-1.39, p = 0.15, respectively. Compared with PBR, PPC led to less grade 3-4 neutropenia and leukopenia but more grade 3-4 nausea. However, hematological toxicity analysis revealed significant heterogeneities.Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology.

  16. Cost-Effectiveness Analysis of Afatinib versus Gefitinib for First-Line Treatment of Advanced EGFR-Mutated Advanced Non-Small Cell Lung Cancers.

    Science.gov (United States)

    Chouaid, Christos; Luciani, Laura; LeLay, Katell; Do, Pascal; Bennouna, Jaafar; Perol, Maurice; Moro-Sibilot, Denis; Vergnenègre, Alain; de Pouvourville, Gérard

    2017-10-01

    The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. For all EGFR mutation-positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations. First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation-positive NSCLCs. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  17. The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden

    Directory of Open Access Journals (Sweden)

    Murphy Daniel R

    2012-10-01

    Full Text Available Abstract Background This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO and Glucocorticoid-induced osteoporosis (GIOP. The study’s objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. Methods A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated. For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD T-Score of −3.0. The GIOP cohorts simulated had an initial BMD T-Score of −2.5. Results The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. Conclusions The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO

  18. Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: a randomized phase II study

    International Nuclear Information System (INIS)

    Lee, Su Jin; Kim, Sungmin; Kim, Moonjin; Lee, Jeeyun; Park, Yeon Hee; Im, Young-Hyuck; Park, Se Hoon

    2015-01-01

    The aim of this study was to assess the efficacy and safety of a combination regimen of capecitabine plus cisplatin (CC) or capecitabine plus paclitaxel (CP) as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma. Patients with recurrent or metastatic esophageal squamous cell carcinoma were enrolled in this open-label, phase II, randomized trial. Patients were assigned to either the CC arm (days [D]1–14 capecitabine 1000 mg/m 2 twice daily + D1 cisplatin 75 mg/m 2 , every 3 weeks) or the CP arm (D1–14 capecitabine 1000 mg/m 2 twice daily + D1, 8 paclitaxel 80 mg/m 2 , every 3 weeks). The primary endpoint of the study was response rate and secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity and quality of life. A total of 94 patients were entered into this study between October 2008 and October 2012, 46 patients in the CC arm and 48 in the CP arm. Patients in both arms received a median of six cycles of treatment (range, 1–14) and the response rates were 57 and 58 % in the cisplatin and paclitaxel arm, respectively. With a median follow-up of 23 months, the median PFS was 5.1 months (95 % CI 4.0–6.2 months) in the cisplatin arm and 6.7 months (95 % CI 4.9–8.5 months) in the paclitaxel arm, whereas the median OS was 10.5 months (95 % CI 9.2–11.9 months) in the cisplatin arm and 13.2 months (95 % CI 9.4–17.0 months) in the paclitaxel arm. Patients in the cisplatin arm were more likely to experience neutropenia and thrombocytopenia, whereas patients in the paclitaxel arm had a higher frequency of neuropathy and alopecia. Quality of life was similar between treatment arms. Both CC and CP regimens were effective and well tolerated as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma

  19. Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China.

    Science.gov (United States)

    Lu, Shun; Ye, Ming; Ding, Lieming; Tan, Fenlai; Fu, Jie; Wu, Bin

    2017-02-07

    Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy.

  20. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

    Science.gov (United States)

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

    2015-06-01

    To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

  1. Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study.

    Science.gov (United States)

    Semvua, Hadija H; Mtabho, Charles M; Fillekes, Quirine; van den Boogaard, Jossy; Kisonga, Riziki M; Mleoh, Liberate; Ndaro, Arnold; Kisanga, Elton R; van der Ven, Andre; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Burger, David M

    2013-01-01

    To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART). A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported. Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

  2. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.

    Science.gov (United States)

    Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-Ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

    2014-12-01

    The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); Paplastic anemia. Copyright© Ferrata Storti Foundation.

  3. A new approach in the first-line treatment of bacterial and mycotic vulvovaginitis with topical lipohydroperoxides and glycyrrhetic acid: a comparative study.

    Science.gov (United States)

    Mainini, G; Rotondi, M; Scaffa, C

    2011-01-01

    PURPOSE OF INVESTIGATIONS: The aim of this randomized controlled trial was to evaluate efficacy and tolerability of a new association of lipohydroperoxides and glycyrrhetic acid on topical treatment of bacterial and mycotic vulvovaginitis. One hundred consecutive patients with bacterial or mycotic vulvovaginitis were randomly assigned to a study group treated with vaginal lipohydroperoxides and a derivative of glycyrrhetic acid for three days (n = 50), and a control group using vaginal antibacterial metronidazole (500 mg) or antimycotic econazole (150 mg) for six days (n = 50). A clinical and microbiological response was achieved in 80.4% and 88.9% in investigational and control group, respectively (p > 0.05). Compared to traditional antimicrobial drugs, the effect appears to be faster and safer, even if not significantly. The 6-month recurrence rate was 7.7% and 5.6% in the investigational and control group, respectively. Topical medication based on lipohydroperoxides and glycyrrhetic acid showed a clinical and microbiological efficacy in the first-line treatment of bacterial and mycotic vulvovaginitis, comparable to conventional drugs.

  4. Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study.

    Science.gov (United States)

    Dragovic, Gordana; Smith, Colette J; Jevtovic, Djordje; Dimitrijevic, Bozana; Kusic, Jovana; Youle, Mike; Johnson, Margaret A

    2016-03-03

    The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH). All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods. 361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p HIV disease, resulting in higher mortality rates than in high income countries, supporting improved testing campaigns for early detection of HIV infection and early introduction of newer cART regimens.

  5. Endovascular Treatment of Phlegmasia Cerulea Dolens with Impending Venous Gangrene: Manual Aspiration Thrombectomy as the First-Line Thrombus Removal Method

    International Nuclear Information System (INIS)

    Oguzkurt, Levent; Ozkan, Ugur; Demirturk, Orhan S.; Gur, Serkan

    2011-01-01

    Purpose: Our purpose was to report the outcome of endovascular treatment with manual aspiration thrombectomy as the first-line thromboablative method for phlegmasia cerulea dolens. Methods: Between October 2006 and May 2010, seven consecutive patients (5 women, 2 men; age range, 31–80 years) with the diagnosis of phlegmasia cerulea dolens secondary to acute iliofemoral deep venous thrombosis had endovascular treatment with manual aspiration thrombectomy. Catheter-directed thrombolysis and stent placement were used as adjunctive procedures. Phlegmasia was left-sided in five and right-sided in two patients. Results: All patients had associated great saphenous vein thrombosis in addition to iliofemoral deep vein thrombosis (DVT). Aspiration thrombectomy completely removed the thrombus from the popliteal vein to the inferior vena cava (IVC) in all cases. Three patients with May-Thurner syndrome had stent placement in the left common iliac vein. Two patients had early recurrences. Repeated aspiration thrombectomy was unsuccessful in one patient. There were no complications related to the procedure. One patient who had been successfully treated died of sepsis and another patient who had unsuccessful repeated interventions had below-the-knee amputation. Overall, the clinical success and survival rates of patients in this study were 86%. On follow-up, three patients with successful treatment were asymptomatic with no deep venous insufficiency. One of these patients died during the 4-month follow-up period. Two patients had mild ankle swelling with deep venous insufficiency. Conclusions: Manual aspiration thrombectomy with adjunctive use of catheter-directed thrombolysis and stent placement is an effective endovascular treatment method with high clinical success and survival rates for phlegmasia cerulean dolens.

  6. The efficacy of modified docetaxel-cisplatin-5-fluorouracil regimen as first-line treatment in patients with alpha-fetoprotein producing gastric carcinoma

    Science.gov (United States)

    Bozkaya, Yakup; Doğan, Mutlu; Yazıcı, Ozan; Erdem, Gökmen Umut; Demirci, Nebi Serkan; Zengin, Nurullah

    2017-01-01

    Alpha-fetoprotein producing gastric carcinoma (AFP-PGC) is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF) as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients. In total, 169 patients (34 with AFP-PGC and 135 with non-AFP-PGC) were included in this study. AFP-PGC patients had more liver metastases than non-AFP-PGC patients (p < 0.001). A decrease in basal AFP levels after three cycles of chemotherapy was significantly different in AFP-PGC group (p = 0.001). Overall disease control rate was 79.4% (partial response [PR] - 44.1%, stable disease [SD] - 35.3%), and 82.2% (complete response - 3%, PR - 36.2%, SD - 43%) in AFP-PGC and non-AFP-PGC patients, respectively. There was no difference between AFP-PGC and non-AFP-PGC groups in overall and progression-free survival rates (11.3 versus 11.4 months and 7.7 versus 7.1 months, respectively). Rates of grade 3-4 hematologic toxicity were 8.8% and 6.7% for neutropenia in AFP-PGC and non-AFP-PGC group, respectively and 5.9% and 7.4% for anemia. In conclusion, mDCF regimen is well-tolerated with acceptable toxicity outcomes in both AFP-PGC and non-AFP-PGC patients. A statistically significant decrease in AFP levels after mDCF regimen indicate that AFP might be considered as a supplemental marker of response to mDCF chemotherapy in AFP-PGC patients. However, further prospective clinical trials are required in this area. PMID:28273032

  7. The efficacy of modified docetaxel-cisplatin-5-fluorouracil regimen as first-line treatment in patients with alpha-fetoprotein producing gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Yakup Bozkaya

    2017-05-01

    Full Text Available Alpha-fetoprotein producing gastric carcinoma (AFP-PGC is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients. In total, 169 patients (34 with AFP-PGC and 135 with non-AFP-PGC were included in this study. AFP-PGC patients had more liver metastases than non-AFP-PGC patients (p < 0.001. A decrease in basal AFP levels after three cycles of chemotherapy was significantly different in AFP-PGC group (p = 0.001.Overall disease control rate was 79.4% (partial response [PR] - 44.1%, stable disease [SD] - 35.3%, and 82.2% (complete response - 3%, PR - 36.2%, SD - 43% in AFP-PGC and non-AFP-PGC patients, respectively. There was no difference between AFP-PGC and non-AFP-PGC groups in overall and progression-free survival rates (11.3 versus 11.4 months and 7.7 versus 7.1 months, respectively. Rates of grade 3-4 hematologic toxicity were 8.8% and 6.7% for neutropenia in AFP-PGC and non-AFP-PGC group, respectively and 5.9% and 7.4% for anemia. In conclusion, mDCF regimen is well-tolerated with acceptable toxicity outcomes in both AFP-PGC and non-AFP-PGC patients. A statistically significant decrease in AFP levels after mDCF regimen indicate that AFP might be considered as a supplemental marker of response to mDCF chemotherapy in AFP-PGC patients. However, further prospective clinical trials are required in this area.

  8. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

    DEFF Research Database (Denmark)

    Fløtten, Ø; Grønberg, B H; Bremnes, R

    2012-01-01

    BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare...... a non-platinum with a platinum combination. METHODS: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0-2. Patients received up to three cycles of vinorelbine 60 mg m(-2) p.o.+gemcitabine 1000 mg m(-2) i.v. day 1 and 8 (VG) or vinorelbine 60 mg m(-2) p.o. day 1 and 8+carboplatin...... was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P=0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P=0.008) and grade IV neutropenia (VG: 7%, VC: 19%, P

  9. PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China.

    Science.gov (United States)

    Wu, Kai-Jie; Pei, Xin-Qi; Tian, Ge; Wu, Da-Peng; Fan, Jin-Hai; Jiang, Yu-Mei; He, Da-Lin

    2018-01-01

    Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.

  10. Endoscopic Injection of Dextranomer/Hyaluronic Acid as First-Line Treatment in 851 Consecutive Children with High-Grade Vesicoureteral Reflux: Efficacy and Long-Term Results.

    Science.gov (United States)

    Friedmacher, Florian; Colhoun, Eric; Puri, Prem

    2018-03-15

    Endoscopic injection of dextranomer/hyaluronic is widely acknowledged as first-line treatment of lower grade vesicoureteral reflux. Our objective was to demonstrate its long-term efficacy and safety in eradicating high-grade reflux. Eight-hundred-fifty-one children (518 girls, 333 boys), median age 2.3 years (2 months-13.7 years), underwent endoscopic correction of high-grade vesicoureteral reflux using dextranomer/hyaluronic acid. Reflux was unilateral in 415 cases and bilateral in 436, comprising 1,287 refluxing units: grade IV in 1,153 (89.6%) and grade V in 134 (10.4%). 99m technetium-dimercaptosuccinic acid imaging identified renal scarring in 317 (37.3%) patients. Follow-up ultrasound and voiding cystourethrogram were performed 3 months post intervention and renal ultrasound annually thereafter. Median follow-up was 8.5 years (6 months-16 years). Overall resolution rate after the first endoscopic injection was 895/1,287 (69.5%): 70.4% in grade IV and 61.9% in grade V, respectively. Reflux resolved after a second injection in 259 (20.1%) and after a third in 133 (10.4%). Persistent reflux after initial treatment was significantly more common in infants reflux resolution, 43 (5.1%) children developed febrile urinary tract infections: 24 (55.8%) in the first, 15 (34.9%) in the second and 4 (9.3%) after ≥3 years. Of these, 6 had reflux recurrence and 8 demonstrated neocontralateral grade III reflux, which was successfully treated with single endoscopic injection of dextranomer/hyaluronic acid. Endoscopic injection of dextranomer/hyaluronic acid is an efficient and safe long-term treatment for grade IV and V vesicoureteral reflux, which can be easily repeated in cases of failure with a high subsequent resolution rate. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Indirect treatment comparison of bevacizumab + interferon-α-2a vs tyrosine kinase inhibitors in first-line metastatic renal cell carcinoma therapy

    Directory of Open Access Journals (Sweden)

    Gerald HJ Mickisch

    2011-01-01

    Full Text Available Gerald HJ Mickisch1, Björn Schwander2, Bernard Escudier3, Joaquim Bellmunt4, José P Maroto5, Camillo Porta6, Stefan Walzer7, Uwe Siebert8,91Department of Urology, Center of Operative Urology Bremen, Bremen, Germany; 2Department of Outcomes Research, AiM GmbH Assessment-in-Medicine, Lörrach, Germany; 3Immunotherapy Unit, Institut Gustave Roussy, Villejuif, France; 4Department of Medical Oncology, University Hospital del Mar UPF, Barcelona, Spain; 5Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 6Department of Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia, Italy; 7Global Health Economics, F Hoffmann-La Roche Pharmaceuticals AG, Basel, Switzerland; 8Department of Public Health, Medical Decision Making and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria; 9Department of Health Policy and Management, Harvard School of Public Health, Boston, MA, USABackground: The vascular endothelial growth factor inhibitor bevacizumab (BEV given in combination with interferon-α-2a (IFN, and the tyrosine kinase inhibitors (TKIs sunitinib (SUN and pazopanib (PAZ, have all shown significant increase in progression-free survival (PFS in first-line metastatic renal-cell carcinoma (mRCC therapy. These targeted therapies are currently competing to be primary choice; hence, in the absence of direct head-to-head comparison, there is a need for valid indirect comparison assessment.Methods: Standard indirect comparison methods were applied to independent review PFS data of the pivotal Phase III trials, to determine indirect treatment comparison hazard-ratios (HR with 95% confidence intervals (95% CI. As BEV+IFN and SUN have been compared to IFN, indirect comparison was enabled by the common IFN comparator arms. As PAZ was compared to placebo (PLA, a connector trial (IFN vs PLA was required for the indirect comparison to BEV

  12. Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Bazarbashi, Shouki; Aljubran, Ali; Alzahrani, Ahmad; Mohieldin, Ahmed; Soudy, Hussein; Shoukri, Mohammed

    2015-01-01

    Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m 2 . Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity

  13. Comparison of gemcitabin, cisplatin, and dexamethasone (GDP), CHOP, and CHOPE in the first-line treatment of peripheral T-cell lymphomas.

    Science.gov (United States)

    Jia, Bo; Hu, Shaoxuan; Yang, Jianliang; Zhou, Shengyu; Liu, Peng; Qin, Yan; Gui, Lin; Yang, Sheng; Lin, Hua; Zhang, Changgong; Xing, Puyuan; Wang, Lin; Dong, Mei; Zhou, Liqiang; Sun, Yan; He, Xiaohui; Shi, Yuankai

    2016-10-01

    Optimal chemotherapy regimen for peripheral T-cell lymphomas (PTCL) has not been fully defined. This study aimed to evaluate the optimal chemotherapy regimen in the first-line treatment for PTCL patients. Between 2003 and 2014, 93 consecutive patients with PTCL were enrolled in this study. Of 93 patients, 42 patients received CHOPE, 40 patients with CHOP, and 11 patients with GDP regimen. Response could be evaluated in 88 of 93 patients at the end of primary treatment. The CR rate for patients received CHOP (n = 38), CHOPE (n = 39), and GDP (n = 11) were 28.9, 51.3, and 45.5%, respectively, (P = 0.132) with an ORR of 65.8, 76.9, and 90.9%, respectively, (P = 0.210). The median follow-up time was 17.1 (1.4-108.3) months. Median progression-free survival (PFS) in CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) groups were 6.0, 15.3, and 9.7 months (P = 0.094) with 1-year PFS of 35.0, 54.8, and 45.5%, respectively, (P = 0.078). One-year OS for patients received CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) were 65.0, 83.3, and 100%, respectively, (P = 0.013) (CHOP vs CHOPE, P = 0.030; CHOP vs GDP, P = 0.024; CHOPE vs GDP, P = 0.174). CHOPE has a trend to improve CR rate, 1-year PFS and OS compared with CHOP alone. GDP shows promising efficacy which worth further exploration in large cohort studies. Clinical experience presented in this study may serve as reference for future large cohort studies.

  14. Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell

    Directory of Open Access Journals (Sweden)

    Jonathan González García

    2017-01-01

    Full Text Available Introduction: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC, and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years. The main treatment regimens used for first-line treatment of NSCLC are: isplatin/pemetrexed (cis/pem, cisplatin/gemcitabine/ bevacizumab (cis/gem/bev, and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev. The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. Methodology: A cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. Results: The PFS obtained in clinical trials with cis/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19 942 €, 15 594 € and 36 095 €, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cis/pem and cis/gem/bev was 19 303 €. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V., due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

  15. The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

    Science.gov (United States)

    Rossi, Giuseppe; Marcheselli, Luigi; Dondi, Alessandra; Bottelli, Chiara; Tucci, Alessandra; Luminari, Stefano; Arcaini, Luca; Merli, Michele; Pulsoni, Alessandro; Boccomini, Carola; Puccini, Benedetta; Micheletti, Moira; Martinelli, Giovanni; Rossi, Andrea; Zilioli, Vittorio Ruggero; Bozzoli, Valentina; Balzarotti, Monica; Bolis, Silvia; Cabras, Maria Giuseppina; Federico, Massimo

    2015-01-01

    Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line. © 2014 Wiley Periodicals, Inc.

  16. Rituximab plus chemotherapy as first-line treatment in Chinese patients with diffuse large B-cell lymphoma in routine practice: a prospective, multicentre, non-interventional study

    International Nuclear Information System (INIS)

    Wu, Jianqiu; Song, Yongping; Su, Liping; Xu, Li; Chen, Tingchao

    2016-01-01

    The efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL. Treatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120 days after the last R-chemo administration. Overall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2 % (complete response [CR], 55.0 %; CR unconfirmed [CRu] 18.2 %; and partial response [PR], 20.9 %). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5 cm negatively correlated with CR + CRu, whereas age and HBsAg positivity negatively correlated with CR. This study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures

  17. Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

    Directory of Open Access Journals (Sweden)

    Verduyn S

    2012-09-01

    .3 (7.0; 9.9 for gefitinib. Conclusions In the Dutch health care setting, the previously established progression free survival benefit of first-line gefitinib in advanced NSCLC EGFR M+ patients in comparison to standard doublet chemotherapy is further supported by the Quality Adjusted PFS, which takes into account the additional health-related quality of life benefits of gefitinib over doublet chemotherapy.

  18. 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

    Science.gov (United States)

    Hecht, J Randolph; Mitchell, Edith P; Yoshino, Takayuki; Welslau, Manfred; Lin, Xun; Chow Maneval, Edna; Paolini, Jolanda; Lechuga, Maria Jose; Kretzschmar, Albrecht

    2015-01-01

    Background Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil) was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Methods Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Results Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with sunitinib. Hematologic toxicity was more common in the sunitinib arm. Conclusion While the results of the sunitinib arm are comparable with those of previously reported FOLFOX combinations, the sunitinib-based combination was associated with more toxicity than that observed with bevacizumab and mFOLFOX6. The bevacizumab arm had an unexpectedly good outcome, and was much better than that seen in the Phase III trials. Combination therapy with sunitinib plus mFOLFOX6 is not recommended for patients with metastatic colorectal cancer. PMID:26109878

  19. 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

    International Nuclear Information System (INIS)

    Hecht, J Randolph; Mitchell, Edith P; Yoshino, Takayuki; Welslau, Manfred; Lin, Xun; Chow Maneval, Edna; Paolini, Jolanda; Lechuga, Maria Jose; Kretzschmar, Albrecht

    2015-01-01

    Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil) was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with sunitinib. Hematologic toxicity was more common in the sunitinib arm. While the results of the sunitinib arm are comparable with those of previously reported FOLFOX combinations, the sunitinib-based combination was associated with more toxicity than that observed with bevacizumab and mFOLFOX6. The bevacizumab arm had an unexpectedly good outcome, and was much better than that seen in the Phase III trials. Combination therapy with sunitinib plus mFOLFOX6 is not recommended for patients with metastatic colorectal cancer

  20. The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis.

    Directory of Open Access Journals (Sweden)

    Han Yan

    Full Text Available The combination of chemotherapy and epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC. This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL, Chinese biomedical literature database (CNKI and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.A total of six randomized controlled trials (RCTs including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS, time to progression (TTP and objective response rate (ORR, compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98-1.12; TTP: HR = 0.94, 95%CI = 0.89-1.00; ORR: RR = 1.07, 95%CI = 0.98-1.17, and no significant difference in OS and progression-free survival (PFS, compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83-1.46; PFS: HR = 0.86, 95% CI = 0.67-1.10. The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10-1.79 and rash (RR = 7.43, 95% CI = 4.56-12.09, compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25-35.93 and fatigue (RR = 9.60, 95% CI = 2.28-40.86 compared with EGFR TKI monotherapy.The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.

  1. Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer

    International Nuclear Information System (INIS)

    Sun, Yan; Cheng, Ying; Hao, Xuezhi; Wang, Jie; Hu, Chengping; Han, Baohui; Liu, Xiaoqing; Zhang, Li; Wan, Huiping; Xia, Zhongjun; Liu, Yunpeng; Li, Wei; Hou, Mei; Zhang, Helong; Xiu, Qingyu; Zhu, Yunzhong; Feng, Jifeng; Qin, Shukui; Luo, Xiaoyan

    2016-01-01

    Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority. From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m 2 , day 1) and amrubicin (40 mg/m 2 , days 1–3) once every 21 days. EP-treated patients received cisplatin (80 mg/m 2 , day 1) and etoposide (100 mg/m 2 , days 1–3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal. Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95 % confidence interval for hazard ratio 0.63–1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8 % vs. 57.3 %, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4 %; EP 44.0 %). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable. AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China. This trial was registered on 10 April 2008 (ClinicalTrials.gov: NCT00660504)

  2. Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study

    NARCIS (Netherlands)

    Homburg, R.R.; Hendriks, M.L.; König, T.E.; Anderson, R.A.; Balen, A.H.; Brincat, M.; Child, T.; Davies, M.; D'Hooghe, T.; Martinez, A; Rajkhowa, M.; Rueda-Saenz, R.; Hompes, P.G.A.; Lambalk, C.B.

    2012-01-01

    BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the

  3. The predictive value of microRNA-126 in relation to first line treatment with capecitabine and oxaliplatin in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Sørensen, Flemming Brandt; Lindebjerg, Jan

    2012-01-01

    MicroRNA-126 is the only microRNA (miRNA) known to be endothelial cell-specific influencing angiogenesis in several ways. The aim of the present study was to analyse the possible predictive value of miRNA-126 in relation to first line capecitabine and oxaliplatin (XELOX) in patients with metastatic...

  4. Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

    Science.gov (United States)

    Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

    2012-01-01

    Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to

  5. Value of {sup 18}F-FDG PET/CT for therapeutic assessment of patients with polymyalgia rheumatica receiving tocilizumab as first-line treatment

    Energy Technology Data Exchange (ETDEWEB)

    Palard-Novello, X. [Brest University Hospital, Department of Nuclear Medicine, Brest Cedex (France); Querellou, S.; Abgral, R.; Salauen, P.Y. [Brest University Hospital, Department of Nuclear Medicine, Brest Cedex (France); Brest University, EA3878, GETBO, IFR148, Brest (France); Gouillou, M. [Institut National de la Sante et de la Recherche Medicale (INSERM), Clinical Investigation Centre (CIC) 1412, Brest (France); Saraux, A.; Devauchelle-Pensec, V. [Brest University Hospital, Department of Rheumatology, Brest (France); Brest University, EA 2216, ESPRI 29, Brest (France); Marhadour, T. [Brest University Hospital, Department of Rheumatology, Brest (France); Garrigues, F. [Brest University Hospital, Department of Radiology, Brest (France)

    2016-04-15

    To evaluate the use of {sup 18}F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR). Patients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman's rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR. Of 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4 mg/l and ESR from 49 to 6.5 mm; all p < 0.05) as did the median SUVmax (from 5.8 to 5.2; p < 0.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; p < 0.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ∇SUVmax and the other parameters including ∇PMR-AS, ∇CRP and ∇ESR in the patient-based and region-based analysis. FDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity. (orig.)

  6. Value of 18F-FDG PET/CT for therapeutic assessment of patients with polymyalgia rheumatica receiving tocilizumab as first-line treatment

    International Nuclear Information System (INIS)

    Palard-Novello, X.; Querellou, S.; Abgral, R.; Salauen, P.Y.; Gouillou, M.; Saraux, A.; Devauchelle-Pensec, V.; Marhadour, T.; Garrigues, F.

    2016-01-01

    To evaluate the use of 18 F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR). Patients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman's rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR. Of 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4 mg/l and ESR from 49 to 6.5 mm; all p < 0.05) as did the median SUVmax (from 5.8 to 5.2; p < 0.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; p < 0.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ∇SUVmax and the other parameters including ∇PMR-AS, ∇CRP and ∇ESR in the patient-based and region-based analysis. FDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity. (orig.)

  7. Cost-effectiveness analysis of entecavir versus lamivudine in the first-line treatment of Australian patients with chronic hepatitis B.

    Science.gov (United States)

    Arnold, Elizabeth; Yuan, Yong; Iloeje, Uchenna; Cook, Greg

    2008-01-01

    Chronic hepatitis B (CHB) virus infection is a major global healthcare problem. The recent introduction of entecavir in Australia for the treatment of CHB patients in the naive treatment setting has triggered significant optimism with regards to improved clinical outcomes for CHB patients. To estimate, from an Australian healthcare perspective, the cost effectiveness of entecavir 0.5 mg/day versus lamivudine 100 mg/day in the treatment of CHB patients naive to nucleos(t)ide therapy. A cost-utility analysis to project the clinical and economic outcomes associated with CHB disease and treatment was conducted by developing two decision-tree models specific to hepatitis B e antigen-positive (HBeAg+ve) and HBeAg-ve CHB patient subsets. This analysis was constructed using the Australian payer perspective of direct costs and outcomes, with indirect medical costs and lost productivity not being included. The study population comprised a hypothetical cohort of 1000 antiviral treatment-naive CHB patients who received either entecavir 0.5 mg/day or lamivudine 100 mg/day at model entry. The population of patients used in this analysis was representative of those patients likely to receive initial antiviral therapy in clinical practice in Australia. The long-term cost effectiveness of entecavir compared with lamivudine in the first-line treatment of CHB patients was expressed as an incremental cost per life-year gained (LYG) or QALY gained. Results revealed that the availability of entecavir 0.5 mg/day as part of the Australian hepatologist's treatment armamentarium should result in significantly lower future rates of compensated cirrhosis (CC), decompensated cirrhosis (DC), and hepatocellular carcinoma (HCC) events (i.e. 54 fewer cases of CC, seven fewer cases of DC, and 20 fewer cases of HCC over the model's timeframe for HBeAg+ve CHB patients, and 69 fewer cases of CC, eight fewer cases of DC and 25 fewer cases of HCC over the model's timeframe for HBeAg-ve CHB patients

  8. Simplified clinical prediction scores to target viral load testing in adults with suspected first line treatment failure in Phnom Penh, Cambodia.

    Directory of Open Access Journals (Sweden)

    Johan van Griensven

    Full Text Available BACKGROUND: For settings with limited laboratory capacity, 2013 World Health Organization (WHO guidelines recommend targeted HIV-1 viral load (VL testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done 'on the spot'. METHODOLOGY/PRINCIPAL: Findings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with 'current CD4 count' instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having 'decrease in CD4 count below baseline value' removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥ 1.5 or ≤ 0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC and 95% confidence intervals (CI. The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33-44; median baseline CD4 count: 94 cells/µL (IQR 28-205, median time on antiretroviral therapy 3.6 years (IQR 2.1-5.1, were included. Forty-five 45 (3.0% individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62-0.75 in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62-0.74, and CPS3, an AUROC of 0.67 (95% CI: 0.61-0.73. The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53-0.65. CONCLUSIONS: Simplified CPSs retained

  9. Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study

    NARCIS (Netherlands)

    Hamers, Raph L.; Schuurman, Rob; Sigaloff, Kim C. E.; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E.; Wellington, Maureen; Osibogun, Akin; Wit, Ferdinand W.; van Vugt, Michèle; Stevens, Wendy S.; de Wit, Tobias F. Rinke

    2012-01-01

    Background The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large

  10. First-line drugs for hypertension.

    Science.gov (United States)

    Wright, James M; Musini, Vijaya M; Gill, Rupam

    2018-04-18

    This is the first update of a review published in 2009. Sustained moderate to severe elevations in resting blood pressure leads to a critically important clinical question: What class of drug to use first-line? This review attempted to answer that question. To quantify the mortality and morbidity effects from different first-line antihypertensive drug classes: thiazides (low-dose and high-dose), beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers (ARB), and alpha-blockers, compared to placebo or no treatment.Secondary objectives: when different antihypertensive drug classes are used as the first-line drug, to quantify the blood pressure lowering effect and the rate of withdrawal due to adverse drug effects, compared to placebo or no treatment. The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. Randomized trials (RCT) of at least one year duration, comparing one of six major drug classes with a placebo or no treatment, in adult patients with blood pressure over 140/90 mmHg at baseline. The majority (over 70%) of the patients in the treatment group were taking the drug class of interest after one year. We included trials with both hypertensive and normotensive patients in this review if the majority (over 70%) of patients had elevated blood pressure, or the trial separately reported outcome data on patients with elevated blood pressure. The outcomes assessed were mortality, stroke, coronary heart disease (CHD), total cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and

  11. HIV-1 drug resistance genotyping from antiretroviral therapy (ART naïve and first-line treatment failures in Djiboutian patients

    Directory of Open Access Journals (Sweden)

    Elmi Abar Aden

    2012-10-01

    Full Text Available Abstract In this study we report the prevalence of antiretroviral drug resistant HIV-1 genotypes of virus isolated from Djiboutian patients who failed first-line antiretroviral therapy (ART and from ART naïve patients. Patients and methods A total of 35 blood samples from 16 patients who showed first-line ART failure (>1000 viral genome copies/ml and 19 ART-naïve patients were collected in Djibouti from October 2009 to December 2009. Both the protease (PR and reverse transcriptase (RT genes were amplified and sequenced using National Agency for AIDS Research (ANRS protocols. The Stanford HIV database algorithm was used for interpretation of resistance data and genotyping. Results Among the 16 patients with first-line ART failure, nine (56.2% showed reverse transcriptase inhibitor-resistant HIV-1 strains: two (12.5% were resistant to nucleoside (NRTI, one (6.25% to non-nucleoside (NNRTI reverse transcriptase inhibitors, and six (37.5% to both. Analysis of the DNA sequencing data indicated that the most common mutations conferring drug resistance were M184V (38% for NRTI and K103N (25% for NNRTI. Only NRTI primary mutations K101Q, K103N and the PI minor mutation L10V were found in ART naïve individuals. No protease inhibitor resistant strains were detected. In our study, we found no detectable resistance in ∼ 44% of all patients who experienced therapeutic failure which was explained by low compliance, co-infection with tuberculosis and malnutrition. Genotyping revealed that 65.7% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C. Conclusion The results of this first study about drug resistance mutations in first-line ART failures show the importance of performing drug resistance mutation test which guides the choice of a second-line regimen. This will improve the management of HIV-infected Djiboutian patients. Virtual slides The virtual slide(s for this article can be found

  12. Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes, after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique

    DEFF Research Database (Denmark)

    Enosse, Sonia; Magnussen, Pascal; Abacassamo, Fatima

    2008-01-01

    BACKGROUND: In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin...... Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here...... haplotype (CIRNI) remained high and only changed marginally from 46% to 53% (P = 0.405) after one year with SP as first-line treatment in the study area. Conversely, the combined Pfdhfr/Pfdhps quintuple mutant haplotype increased from 8% to 26% (P = 0.005). The frequency of the chloroquine resistance...

  13. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study

    International Nuclear Information System (INIS)

    Thaler, Josef; Köhne, Claus-Henning; Karthaus, Meinolf; Mineur, Laurent; Greil, Richard; Letocha, Henry; Hofheinz, Ralf; Fernebro, Eva; Gamelin, Erick; Baños, Ana

    2012-01-01

    Integument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial. Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity. 154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity. First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity. ClinicalTrials.gov NCT00508404

  14. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study

    Directory of Open Access Journals (Sweden)

    Thaler Josef

    2012-09-01

    Full Text Available Abstract Background Integument-related toxicities are common during epidermal growth factor receptor (EGFR-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial. Methods Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity. Results 154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59; most (98% experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]. Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56% compared with those with grade 0/1 (29%. Mean overall EQ-5D health state index scores (0.81 vs. 0.78, health rating scores (72.5 vs. 71.0 and QLQ-C30 global health status scores (65.8 vs. 66.7 were comparable at baseline vs. safety follow-up (8 weeks after completion, respectively and appeared unaffected by skin toxicity severity. Conclusions First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument

  15. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    Energy Technology Data Exchange (ETDEWEB)

    Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

    2014-08-15

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

  16. Hormonal therapy followed by chemotherapy or the reverse sequence as first-line treatment of hormone-responsive, human epidermal growth factor receptor-2 negative metastatic breast cancer patients: results of an observational study.

    Science.gov (United States)

    Bighin, Claudia; Dozin, Beatrice; Poggio, Francesca; Ceppi, Marcello; Bruzzi, Paolo; D'Alonzo, Alessia; Levaggi, Alessia; Giraudi, Sara; Lambertini, Matteo; Miglietta, Loredana; Vaglica, Marina; Fontana, Vincenzo; Iacono, Giuseppina; Pronzato, Paolo; Del Mastro, Lucia

    2017-07-04

    Introduction Although hormonal-therapy is the preferred first-line treatment for hormone-responsive, HER2 negative metastatic breast cancer, no data from clinical trials support the choice between hormonal-therapy and chemotherapy.Methods Patients were divided into two groups according to the treatment: chemotherapy or hormonal-therapy. Outcomes in terms of clinical benefit and median overall survival (OS) were retrospectively evaluated in the two groups. To calculate the time spent in chemotherapy with respect to OS in the two groups, the proportion of patients in chemotherapy relative to those present in either group was computed at every day from the start of therapy.Results From 1999 to 2013, 119 patients received first-line hormonal-therapy (HT-first group) and 100 first-line chemotherapy (CT-first group). Patients in the CT-first group were younger and with poorer prognostic factors as compared to those in HT-first group. Clinical benefit (77 vs 81%) and median OS (50.7 vs 51.1 months) were similar in the two groups. Time spent in chemotherapy was significantly longer during the first 3 years in CT-first group (54-34%) as compared to the HT-first group (11-18%). This difference decreased after the third year and overall was 28% in the CT-first group and 18% in the HT-first group.Conclusions The sequence first-line chemotherapy followed by hormonal-therapy, as compared with the opposite sequence, is associated with a longer time of OS spent in chemotherapy. However, despite the poorer prognostic factors, patients in the CT-first group had a superimposable OS than those in the HT-first group.

  17. Safety and Efficacy of Fingolimod and Natalizumab in Multiple Sclerosis After the Failure of First-Line Therapy: Single Center Experience Based on the Treatment of Forty-Four Patients.

    Science.gov (United States)

    Puz, Przemysław; Lasek-Bal, Anetta

    2016-11-10

    BACKGROUND In Poland, natalizumab or fingolimod treatment can be delivered as a second-line therapy to those patients with relapsing-remitting multiple sclerosis (RRMS) who demonstrated no response to interferon or glatiramer acetate treatment for a minimum of one year. MATERIAL AND METHODS Analysis covered 44 RRMS patients switched from first- to second-line therapy. The annualized relapse rate, disability progression (assessed with Expanded Disability Status Scale, EDSS) and MRI results (new or enlarged T2 lesions and new Gd-positive lesions) before and after switching were compared. The occurrence of adverse events was also assessed. RESULTS The annualized relapse rate for second-line therapy was significantly lower than for first-line therapy (0.35±0.74 vs. 2.13±0.87, p=0.00005). Median of EDSS progression with first-line therapy was significantly higher than that with natalizumab or fingolimod treatment (p=0.00002). The mean number of new or enlarged T2 and Gd+ lesions in MRI after one-year second-line treatment was significantly lower in comparison to lesions in MRI performed at the end of the first-line therapy (for T2: 0.61 vs. 4.56, p=0.0004; for Gd+: 0.13 vs. 1.98, p=0.0009). No significant differences in the clinical data, MRI results, and side effects between fingolimod and natalizumab patients have been observed. CONCLUSIONS Treatment with natalizumab or fingolimod as a second-line therapy in RRMS patients is safe and effective. Less restrictive criteria for switching should be considered.

  18. Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02).

    Science.gov (United States)

    Tahara, M; Kiyota, N; Yokota, T; Hasegawa, Y; Muro, K; Takahashi, S; Onoe, T; Homma, A; Taguchi, J; Suzuki, M; Minato, K; Yane, K; Ueda, S; Hara, H; Saijo, K; Yamanaka, T

    2018-04-01

    The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. The PCE regimen shows promising

  19. Clinical study of combined use of tomudex (raltitrexed) and xeloda (capecitabine) as first-line treatment for patients with metastasizing colorectal cancer.

    Science.gov (United States)

    Vakhabova, J V; Semenov, N N; Dobrova, N V; Lichinitser, M R

    2008-02-01

    We studied the efficiency of combined chemotherapy with tomudex and xeloda preparations in patients with metastasizing colorectal cancer. The treatment (240 courses) was effective in 75% patients. Time median before progression was 6.3 months, mean durations of partial remission and stabilization were 7.8 months, total survival 15.5 months, total survival after effective treatment was 18.2 months. The most prevalent manifestations of III-IV degree toxicity were neutropenia, diarrhea, and asthenia. Other symptoms of toxicity (increased transaminase level, bilirubin, nausea, vomiting) were observed in less than 3% courses. Thus, treatment with tomudex and xeloda are effective and safe for outpatient chemotherapy.

  20. High rates of regimen change due to drug toxicity among a cohort of South Indian adults with HIV infection initiated on generic, first-line antiretroviral treatment.

    Science.gov (United States)

    Sivadasan, Ajith; Abraham, O C; Rupali, Priscilla; Pulimood, Susanne A; Rajan, Joyce; Rajkumar, S; Zachariah, Anand; Kannangai, Rajesh; Kandathil, Abraham Joseph; Sridharan, G; Mathai, Dilip

    2009-05-01

    To determine the rates, reasons and predictors of treatment change of the initial antiretroviral treatment (ART) regimen in HIV-infected south Indian adults. In this prospective cohort study, ART-naive adults initiated on generic, fixed dose combination ART as per the National AIDS Control Organization guidelines were followed up at an academic medical center. Treatment change was defined as any event which necessitated a change in or discontinuation of the initial ART regimen. Two hundred and thirty persons with HIV infection (males 74.8% and median age 37 years) were followed up for median duration of 48 weeks. The majority (98.7%) had acquired HIV infection through the heterosexual route. Most (70.4%) had advanced IV infection (WHO clinical stage 3 or 4) and 78% had CD4+ T-lymphocyte counts below 200 cells/microL. The initial ART regimens used were: Lamivudine (3TC) with Stavudine (d4T) (in 76%) or Azidothymidine (AZT) and Nevirapine (NVP) (in 86%) or Efavirenz (EFV). The cumulative incidence of treatment change was 39.6% (91 patients). Drug toxicity (WHO grade 3 or 4) was the reason for treatment change among 62 (27%) (incidence rate 35.9/100 person-years). The most common toxicities were attributable to the thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs), d4T and AZT [lactic acidosis (8.7%), anemia (7%) and peripheral neuropathy (5.2%)]. The other toxicities were rash (3.9%) and hepatitis (1.3%) due to NVP. The mortality (4.6/100 person-years) and disease progression rates (4.1/100 person-years) were low. The ART regimens used in this study were effective in decreasing disease progression and death. However, they were associated with high rates of drug toxicities, particularly those attributable to thymidine analogue NRTI. As efforts are made to improve access to ART, treatment regimens chosen should not only be potent, but also safe.

  1. Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study

    NARCIS (Netherlands)

    Semvua, H.H.; Mtabho, C.M.; Fillekes, Q.; Boogaard, J. van den; Kisonga, R.M.; Mleoh, L.; Ndaro, A.; Kisanga, E.R.; Ven, A. van der; Aarnoutse, R.E.; Kibiki, G.S.; Boeree, M.J.; Burger, D.M.

    2013-01-01

    BACKGROUND: To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. METHODS: This was a Phase II open-label multiple dose

  2. Cost-utility analysis of dasatinib and nilotinib in patients with chronic myeloid leukemia refractory to first-line treatment with imatinib in Thailand.

    Science.gov (United States)

    Kulpeng, Wantanee; Sompitak, Sumalai; Jootar, Saengsuree; Chansung, Kanchana; Teerawattananon, Yot

    2014-04-01

    Recently, the second-generation tyrosine kinase inhibitors dasatinib and nilotinib have emerged as alternative treatments in patients with chronic myeloid leukemia (CML) who are resistant to or intolerant of imatinib. This article aimed to assess the cost utility and budget impact of using dasatinib or nilotinib, rather than high-dose (800-mg/d) imatinib, in patients with chronic phase (CP) CML who are resistant to standard-dose (400-mg/d) imatinib in Thailand. A Markov simulation model was developed and used to estimate the lifetime costs and outcomes of treating patients aged ≥38 years with CP-CML. The efficacy parameters were synthesized from a systematic review. Utilities using the European Quality of Life-5 Dimensions tool and costs were obtained from the Thai CML population. Costs and outcomes were compared and presented as the incremental cost-effectiveness ratio in 2011 Thai baht (THB) per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty. From a societal perspective, treatment with dasatinib was found to yield more QALYs (2.13) at a lower cost (THB 1,631,331) per person than high-dose imatinib. Nilotinib treatment was also found to be more cost-effective than high-dose imatinib, producing an incremental cost-effectiveness ratio of THB 83,328 per QALY gained. This treatment option also resulted in the highest number of QALYs gained of all of the treatment options. The costs of providing dasatinib, nilotinib, and high-dose imatinib were estimated at THB 5 billion, THB 6 billion, and THB 7 billion, respectively. Treatment with dasatinib or nilotinib is likely to be more cost-effective than treatment with high-dose imatinib in CP-CML patients who do not respond positively to standard-dose imatinib in the Thai context. Dasatinib was found to be more cost-effective than nilotinib. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  3. A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care

    DEFF Research Database (Denmark)

    Sørensen, Jan; Stage, Kurt B; Damsbo, Niels

    2007-01-01

    The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three-path dec...... clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.......The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three......, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS costs. Analyses were conducted from healthcare system and societal perspectives. The human capital approach was used to estimate societal cost of lost productivity. Costs were reported...

  4. Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar.

    Science.gov (United States)

    Thiha, Nay; Chinnakali, Palanivel; Harries, Anthony D; Shwe, Myint; Balathandan, Thanumalaya Perumal; Thein Than Tun, Sai; Das, Mrinalini; Tin, Htay Htay; Yi, Yi; Babin, François Xavier; Lwin, Thi Thi; Clevenbergh, Philippe Albert

    2016-01-01

    WHO recommends that stavudine is phased out of antiretroviral therapy (ART) programmes and replaced with tenofovir (TDF) for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL) before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment. Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR) to identify associated factors using log binomial regression. Of 4934 patients tested, 4324 (87%) had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8) compared to 25-44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2) compared to the public sector. This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries.

  5. Safety and treatment outcomes of first-line pazopanib in renal cell carcinoma: A prospective observational study in a single Malaysia tertiary hospital

    Directory of Open Access Journals (Sweden)

    Azmi Nor Mohd Farez Ahmat

    2017-12-01

    Full Text Available Introduction: Pazopanib is the standard of care for metastatic renal cell carcinoma (mRCC. Previous studies on this indication were limited to patients who were selected on the basis of a fairly preserved performance status and normal organ function. Thus, the clinical trial population may not be representative of all patients seen in real-world practice. Based on these considerations, this prospective single-centre observational study was designed to evaluate the treatment outcomes and safety profile of pazopanib in Malaysian population. Patients and methods: Patients prescribed with pazopanib between June 2015 and June 2017 were recruited and followed up for 2-years or till death whichever comes first. Progression-free survival (PFS and overall survival (OS were evaluated. Multivariate and survival analysis were performed. Results: Twenty-seven patients were treated with pazopanib where 89% had clear cell histology.  Sixteen patients (59% were intermediate risk and 41% were poor risk based on Memorial Sloan Kettering Cancer Center (MSKCC criteria. All patients experienced at least one adverse event. The most common were cutaneous toxicity (92% followed by proteinuria, hypertension, diarrhoea and mucositis. Treatment interruption was needed in 15 patients. The median PFS and OS were 9.57 months and 15.5 months, respectively. In multivariate analysis, MSKCC risk score demonstrates strong predictive treatment outcome. The median PFS was 14.5 months in intermediate risk and 3.96 months in poor risk (OR: 0.2, p<0.001. However, the median OS is still immature to be reported since 63% of intermediate risk group is still alive at 2-years follow-up. Conclusion: In mRCC patients, treatment with pazopanib was effective in patients with intermediate risk group. In terms of safety, patient tolerated pazopanib quite well with mostly experienced grade 1 to 2 adverse events.

  6. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hagman, H; Frödin, J-E; Berglund, Å

    2016-01-01

    without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev ± erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression...... to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. CLINICALTRIALSGOV: NCT01229813....

  7. Treatment outcomes of HIV-positive patients on first-line antiretroviral therapy in private versus public HIV clinics in Johannesburg, South Africa

    Directory of Open Access Journals (Sweden)

    Moyo F

    2016-03-01

    Full Text Available Faith Moyo,1 Charles Chasela,2,3 Alana T Brennan,1,4 Osman Ebrahim,5 Ian M Sanne,1,6 Lawrence Long,1 Denise Evans1 1Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2Epidemiology and Biostatistics Department, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3Epidemiology and Strategic Information (ESI, HIV/AIDS/STIs and TB, Human Sciences Research Council, Pretoria, South Africa; 4Center for Global Health and Development, Boston University, Boston, MA, USA; 5Brenthurst Clinic, Parktown, South Africa; 6Right to Care, Helen Joseph Hospital, Westdene, Johannesburg, South Africa Background: Despite the widely documented success of antiretroviral therapy (ART, stakeholders continue to face the challenges of poor HIV treatment outcomes. While many studies have investigated patient-level causes of poor treatment outcomes, data on the effect of health systems on ART outcomes are scarce.Objective: We compare treatment outcomes among patients receiving HIV care and treatment at a public and private HIV clinic in Johannesburg, South Africa.Patients and methods: This was a retrospective cohort analysis of ART naïve adults (≥18.0 years, initiating ART at a public or private clinic in Johannesburg between July 01, 2007 and December 31, 2012. Cox proportional-hazards regression was used to identify baseline predictors of mortality and loss to follow-up (>3 months late for the last scheduled visit. Generalized estimating equations were used to determine predictors of failure to suppress viral load (≥400 copies/mL while the Wilcoxon rank-sum test was used to compare the median absolute change in CD4 count from baseline to 12 months post-ART initiation.Results: 12,865 patients initiated ART at the public clinic compared to 610 at the private

  8. A retrospective case-cohort study comparing treatment outcomes in abacavir versus stavudine containing first line antiretroviral treatment regimens in children <3yrs old, at a paediatric programme based in Soweto, South Africa

    Science.gov (United States)

    Otwombe, Kennedy; Lazarus, Erica; Liberty, Afaaf; Gray, Glenda E.; Greeff, Oppel B. W.; Violari, Avy

    2017-01-01

    Introduction The current World Health Organization guideline for first line antiretroviral therapy (ART) in HIV-infected children recommends the use of abacavir and lamivudine as nucleoside backbones and no longer includes stavudine. We compared treatment outcomes with abacavir (ABC) versus stavudine (d4T) in a cohort of HIV-1 infected children 6 and 12 months after antiretroviral therapy was initiated. Methods This was a retrospective case-cohort study, using programmatic data from children enrolled in the Paediatric Wellness Programme at the Perinatal HIV Research Unit in Soweto, South Africa between 2005 and 2013. Children on abacavir/stavudine who had initiated ART at age 90% for ABC and d4T were similar too (95% in ABC vs. 86% in d4T, p = 0.10). The proportion of children who died over 12 months was 3.5% in the ABC and 7.9% in the d4T group (p = 0.27). Similarly, the anthropometric measures were comparable. Conclusions It is reassuring that in the short term, in this group of patients, the treatment outcomes were similar. PMID:28686654

  9. OS02.1 Multicenter pilot study of radio-chemotherapy as first-line treatment for adults with medulloblastoma - the NOA-07 trial

    Science.gov (United States)

    Beier, D.; Proescholdt, M.; Reinert, C.; Hattingen, E.; Seidel, C.; Dirven, L.; Lürding, R.; Pfister, S.; Pietsch, T.; Hau, P.

    2017-01-01

    Abstract Background: Medulloblastoma in adult patients has a low incidence, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. In contrast to children, no prospective data on the feasibility of radio-chemotherapy in adults exists. The German Neuro-Oncology Working Group (NOA) performed a prospective multicenter single-arm Phase II trial to evaluate the feasibility and toxicity of radio-chemotherapy in this population. Methods: The NOA-07 trial combined cranio-spinal irradiation with vincristine, followed by a maximum of eight cycles of cisplatin, lomustine and vincristine. Adverse events, imaging and progression patterns, combined histological and genetic markers, health-related quality of life (HRQoL) and cognition were evaluated prospectively. The primary endpoints were the rate of toxicity-related treatment terminations after four cycles of chemotherapy, and the toxicity profile. Findings: Thirty patients were evaluable. Fifty percent of patients showed classic, and 50% desmoplastic-nodular histology. Sixty-eight percent of patients were genetically classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13.6% in wingless (WNT), and 17.7% in Non-WNT/Non-SHH (Group 4). Four cycles of chemotherapy were feasible in the majority of patients (n=21; 70.0%). Leukopenia was the major toxicity, with 79 events of CTC grade 3 and 4 in 17 patients. Polyneuropathy and ototoxicity were the only grade 3 or 4 non-haematological toxicities during the active treatment phase and occurred 12 times in eight patients and one time in one patient, respectively. Events were also calculated per cycle and showed an increase of toxicity over treatment time. Feasibility appeared to be age-dependent, leading to application of four cycles of chemotherapy in 72.7% of patients below age 45 and 62.5% of patients 45 or above. Testing for all eight adjuvant cycles revealed that 45.5% of all patients younger than 45 years completed

  10. Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis.

    Science.gov (United States)

    Kanters, Steve; Vitoria, Marco; Doherty, Meg; Socias, Maria Eugenia; Ford, Nathan; Forrest, Jamie I; Popoff, Evan; Bansback, Nick; Nsanzimana, Sabin; Thorlund, Kristian; Mills, Edward J

    2016-11-01

    New antiretroviral therapy (ART) regimens for HIV could improve clinical outcomes for patients. To inform global guidelines, we aimed to assess the comparative effectiveness of recommended ART regimens for HIV in ART-naive patients. For this systematic review and network meta-analysis, we searched for randomised clinical trials published up to July 5, 2015, comparing recommended antiretroviral regimens in treatment-naive adults and adolescents (aged 12 years or older) with HIV. We extracted data on trial and patient characteristics, and the following primary outcomes: viral suppression, mortality, AIDS defining illnesses, discontinuations, discontinuations due to adverse events, and serious adverse events. We synthesised data using network meta-analyses in a Bayesian framework and included older treatments, such as indinavir, to serve as connecting nodes. We defined network nodes in terms of specific antivirals rather than specific ART regimens. We categorised backbone regimens and adjusted for them through group-specific meta-regression. We used the GRADE framework to interpret the strength of inference. We identified 5865 citations through database searches and other sources, of which, 126 articles related to 71 unique trials were included in the network analysis, including 34 032 patients randomly assigned to 161 treatment groups. For viral suppression at 48 weeks, compared with efavirenz, the odds ratio (OR) for viral suppression was 1·87 (95% credible interval [CrI] 1·34-2·64) with dolutegravir and 1·40 (1·02-1·96) with raltegravir; with respect to viral suppression, low-dose efavirenz was similar to all other treatments. Both low-dose efavirenz and integrase strand transfer inhibitors tended to be protective of discontinuations due to adverse events relative to normal-dose efavirenz. The most protective effect relative to efavirenz in network meta-analyses was that of dolutegravir (OR 0·26, 95% CrI 0·14-0·47), followed by low-dose efavirenz (0·39

  11. Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer.

    Science.gov (United States)

    Socinski, Mark A; Govindan, Ramaswamy; Spigel, David

    2012-10-01

    Treatments for non-small cell lung cancer (NSCLC) are based on the broad categories of squamous or non-squamous histology. Frontline treatment options include pemetrexed and cisplatin, pemetrexed and a taxane, gemcitabine with cisplatin, and the addition of bevacizumab to a taxane and carboplatin. Pemetrexed is used for maintenance therapy for non-squamous NSCLC, whereas patients with squamous NSCLC lack easy options for maintenance therapy. nab-Paclitaxel overcomes the solubility and toxicity issues of solvent-based paclitaxel, and the albumin in nab-paclitaxel improves the concentration of the drug in the tumor. A recent phase III trial in NSCLC compared nab-paclitaxel with carboplatin versus solvent-based paclitaxel with carboplatin, and found improved overall response rates (ORRs) in the nab-paclitaxel arm (33% vs 25%; P=.005). In a subset analysis, NSCLC patients with squamous histology had a higher ORR (41%) with nab-paclitaxel than with solvent-based paclitaxel (24%; P<.001). Another subset analysis found that patients ages 70 years and older had improved overall survival (median 19.9 months) with nab-paclitaxel compared with solvent-based paclitaxel (median 10.4 months; P=.009). Patients in the nab-paclitaxel arm had less neuropathy, less hearing loss, and fewer interruptions in daily living than patients in the solvent-based paclitaxel arm.

  12. A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care.

    Science.gov (United States)

    Sørensen, Jan; Stage, Kurt B; Damsbo, Niels; Le Lay, Agathe; Hemels, Michiel E

    2007-01-01

    The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three-path decision analytic model with a 6-month horizon was used. All patients started at the primary care path and were referred to outpatient or inpatient secondary care in the case of insufficient response to treatment. Model inputs included drug-specific probabilities derived from systematic literature review, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS escitalopram (64.1%) than citalopram (58.9%). From both perspectives, the total expected cost per successfully treated patient was lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for citalopram (DKK 25,778 healthcare, DKK 87,786 societal). Remission rates and costs were similar for escitalopram and venlafaxine. Robustness of the findings was verified in multivariate sensitivity analyses. For patients in primary care, escitalopram appears to be a cost-effective alternative to (generic) citalopram, with greater clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.

  13. A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France

    Directory of Open Access Journals (Sweden)

    Taipale K

    2017-08-01

    Full Text Available Kaisa Taipale,1 Katherine B Winfree,2 Mark Boye,2 Mickael Basson,3 Ghassan Sleilaty,4 James Eaton,5 Rachel Evans,5 Christos Chouaid6 1Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Corporate Affairs, Lilly France, Neuilly-sur-Seine, 4Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France; 5ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK; 6Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France Background: Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS and overall survival (OS relative to gemcitabine + cisplatin (induction sequences or best supportive care (BSC (maintenance sequences. Modeled health-care benefits were expressed as life-years (LYs and quality-adjusted LYs (QALYs (estimated using French EuroQol five-dimension questionnaire tariffs. The study was conducted from the payer perspective (National Health Insurance. Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results: Base-case results showed pemetrexed

  14. Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer

    DEFF Research Database (Denmark)

    Perez, Edith A; López-Vega, José Manuel; Petit, Thierry

    2016-01-01

    .2% (95% CI 63.8-82.9) in intent-to-treat patients with measurable disease (89/106 [84.0%]). Median PFS was 14.3 months (95% CI 11.2-17.5) in the intent-to-treat population. Treatment was reasonably well tolerated, with no unexpected toxicities. Diarrhea (61/106 patients [57.5%]) and neutropenia (54....../106 [50.9%]) were the most common adverse events (AEs); neutropenia (33/106 [31.1%]) and leukopenia (14/106 [13.2%]) were the most common grade ≥3 AEs. Serious AEs were reported in 32/106 (30.2%) patients. AEs led to study drug discontinuation in 36/106 patients (34.0%). Eighteen of 106 patients (17...

  15. Economic evaluation of everolimus versus sorafenib for the treatment of metastatic renal cell carcinoma after failure of first-line sunitinib.

    Science.gov (United States)

    Casciano, Roman; Chulikavit, Maruit; Di Lorenzo, Giuseppe; Liu, Zhimei; Baladi, Jean-Francois; Wang, Xufang; Robertson, Justin; Garrison, Lou

    2011-01-01

    A recent indirect comparison study showed that sunitinib-refractory metastatic renal cell carcinoma (mRCC) patients treated with everolimus are expected to have improved overall survival outcomes compared to patients treated with sorafenib. This analysis examines the likely cost-effectiveness of everolimus versus sorafenib in this setting from a US payer perspective. A Markov model was developed to simulate a cohort of sunitinib-refractory mRCC patients and to estimate the cost per incremental life-years gained (LYG) and quality-adjusted life-years (QALYs) gained. Markov states included are stable disease without adverse events, stable disease with adverse events, disease progression, and death. Transition probabilities were estimated using a subset of the RECORD-1 patient population receiving everolimus after sunitinib, and a comparable population receiving sorafenib in a single-arm phase II study. Costs of antitumor therapies were based on wholesale acquisition cost. Health state costs accounted for physician visits, tests, adverse events, postprogression therapy, and end-of-life care. The model extrapolated beyond the trial time horizon for up to 6 years based on published trial data. Deterministic and probabilistic sensitivity analyses were conducted. The estimated gain over sorafenib treatment was 1.273 LYs (0.916 QALYs) at an incremental cost of $81,643. The deterministic analysis resulted in an incremental cost-effectiveness ratio (ICER) of $64,155/LYG ($89,160/QALY). The probabilistic sensitivity analysis demonstrated that results were highly consistent across simulations. As the ICER fell within the cost per QALY range for many other widely used oncology medicines, everolimus is projected to be a cost-effective treatment relative to sorafenib for sunitinib-refractory mRCC. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  16. Economic Analysis of First-Line Treatment with Cetuximab or Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer in England.

    Science.gov (United States)

    Tikhonova, Irina A; Huxley, Nicola; Snowsill, Tristan; Crathorne, Louise; Varley-Campbell, Jo; Napier, Mark; Hoyle, Martin

    2018-03-01

    Combination therapies with cetuximab (Erbitux ® ; Merck Serono UK Ltd) and panitumumab (Vectibix ® ; Amgen UK Ltd) are shown to be less effective in adults with metastatic colorectal cancer who have mutations in exons 2, 3 and 4 of KRAS and NRAS oncogenes from the rat sarcoma (RAS) family. The objective of the study was to estimate the cost effectiveness of these drugs in patients with previously untreated RAS wild-type (i.e. non-mutated) metastatic colorectal cancer, not eligible for liver resection at baseline, from the UK National Health Service and Personal Social Services perspective. We constructed a partitioned survival model to evaluate the long-term costs and benefits of cetuximab and panitumumab combined with either FOLFOX (folinic acid, fluorouracil and oxaliplatin) or FOLFIRI (folinic acid, fluorouracil and irinotecan) vs. FOLFOX or FOLFIRI alone. The economic analysis was based on three randomised controlled trials. Costs and quality-adjusted life-years were discounted at 3.5% per annum. Based on the evidence available, both drugs fulfil the National Institute for Health and Care Excellence's end-of-life criteria. In the analysis, assuming discount prices for the drugs from patient access schemes agreed by the drug manufacturers with the Department of Health, predicted mean incremental cost-effectiveness ratios for cetuximab + FOLFOX, panitumumab + FOLFOX and cetuximab + FOLFIRI compared with chemotherapy alone appeared cost-effective at the National Institute for Health and Care Excellence's threshold of £50,000 per quality-adjusted life-year gained, applicable to end-of-life treatments. Cetuximab and panitumumab were recommended by the National Institute for Health and Care Excellence for patients with previously untreated RAS wild-type metastatic colorectal cancer, not eligible for liver resection at baseline, for use within the National Health Service in England. Both treatments are available via the UK Cancer Drugs Fund.

  17. A cost-benefit analysis of bevacizumab in combination with paclitaxel in the first-line treatment of patients with metastatic breast cancer.

    Science.gov (United States)

    Montero, Alberto J; Avancha, Kiran; Glück, Stefan; Lopes, Gilberto

    2012-04-01

    Bevacizumab in combination with chemotherapy increases progression-free survival (PFS), but not overall survival when compared to chemotherapy alone in the treatment of metastatic breast cancer (MBC). Recently in November, 2011 the Food and drug administration revoked approval of bevacizumab in combination with paclitaxel for the treatment of MBC. The European Medicines Agency, in contrast, maintained its approval of bevacizumab in MBC. While neither agency considers health economics in their decision-making process, one of the greatest challenges in oncology practice today is to reconcile hard-won small incremental clinical benefits with exponentially rising costs. To inform policy-makers in the US, this study aimed to assess the cost-effectiveness of bevacizumab/paclitaxel in MBC, from a payer perspective. We created a decision analytical model using efficacy and adverse events data from the ECOG 2100 trial. Health utilities were derived from available literature. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2010 US dollars. Quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. Sensitivity analyses were performed. Bevacizumab added 0.49 years of PFS and 0.135 QALY with an incremental cost of $100,300, and therefore a cost of $204,000 per year of PFS gained and an ICER of $745,000 per QALY. The main drivers of the model were drug acquisition cost, PFS, and health utility values. Using a threshold of $150,000/QALY, drug price would have to be reduced by nearly 80% or alternatively PFS increased by 10 months to make bevacizumab cost-effective. The results of the model were robust in sensitivity analyses. Bevacizumab plus paclitaxel is not cost-effective in treating MBC. Value-based pricing and the development of biomarkers to improve patient selection are needed to better define the role of the drug in this population.

  18. Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

    Science.gov (United States)

    Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

    2016-01-01

    This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced. (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas, the secondary endpoint was overall survival(OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance was determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR.sensitive mutation.

  19. Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation

    Directory of Open Access Journals (Sweden)

    Xiao Zhao

    2014-01-01

    Full Text Available Objective: This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. Patients and Methods: This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV lung adenocarcinoma with epidermal growth factor receptor (EGFR-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS. Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test. Results: The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Conclusion: Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

  20. Cost-Effectiveness of Nivolumab-Ipilimumab Combination Therapy Compared with Monotherapy for First-Line Treatment of Metastatic Melanoma in the United States.

    Science.gov (United States)

    Oh, Anna; Tran, Dang M; McDowell, Leann C; Keyvani, Dor; Barcelon, Jay Andrew; Merino, Oscar; Wilson, Leslie

    2017-06-01

    The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients. To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients. A 3-state Markov model (PD-L1 positive stable disease, PD-L1 negative stable disease, and progression and/or death) was developed using a U.S. societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free (PF) survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 U.S. dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. Nivolumab-ipilimumab combination therapy was not the cost-effective choice ($454,092 per PF quality-adjusted life-year [QALY]) compared with nivolumab monotherapy in a base case analysis at a willingness-to-pay threshold of $100,000 per PFQALY. Combination therapy and nivolumab monotherapy were cost-effective choices compared with ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment, but combination

  1. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment

    Directory of Open Access Journals (Sweden)

    Laura Muinelo-Romay

    2014-01-01

    Full Text Available In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC and their utility for therapy monitoring in non-small cell lung cancer (NSCLC. A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells were counted. At baseline 18 (41.9% patients were positive for intact CTC count and 10 (23.2% of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ³5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively. Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other “objects” such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

  2. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Muinelo-Romay, Laura; Vieito, Maria; Abalo, Alicia; Alonso Nocelo, Marta; Barón, Francisco; Anido, Urbano; Brozos, Elena; Vázquez, Francisca; Aguín, Santiago; Abal, Miguel; López López, Rafael, E-mail: rafael.lopez.lopez@sergas.es [Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela (Spain)

    2014-01-21

    In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ≥5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other “objects” such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

  3. Modified biweekly cisplatin, docetaxel plus cetuximab (TPEx) as first-line treatment for patients with recurrent/metastatic head and neck cancer.

    Science.gov (United States)

    Fuchs, Hannah; Pammer, Johannes; Minichsdorfer, Christoph; Posch, Doris; Kornek, Gabriela; Aretin, Marie-Bernadette; Fuereder, Thorsten

    2018-02-07

    Three weekly high-dose chemotherapy regimens in combination with weekly cetuximab are the treatment of choice for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN), although the majority of patients suffer from severe side effects. Thus, we investigated the efficacy and safety of an alternative, more convenient and less toxic biweekly modified cisplatin, docetaxel plus cetuximab (TPEx) regimen in this retrospective analysis. Thirty-eight patients receiving off-protocol cisplatin (50 mg/m 2 ) in combination with docetaxel (50 mg/m 2 ) plus cetuximab (500 mg/m 2 ) every other week were included. Data collection included baseline demographic, response rate (ORR) and toxicity data as well as disease control rate, overall survival (OS) and progression-free survival (PFS). The median age was 60 years, and the majority of patients suffered from oral cavity carcinomas (44.7%) followed by oropharyngeal (28.9%) and laryngeal (17.9%) carcinomas. The ORR was 50%, and four (10.5%) patients achieved a complete response, while 15 (39.5%) patients had a partial response. The OS and PFS were 10.8 months (95% CI 6.7-14.2) and 6.3 months (95% CI 5.7-6.8), respectively. The one-year survival rate was 44.7%. The therapy was well tolerated, and the most common grade 3/4 adverse events were myelosuppression (13.2%), hypomagnesaemia (23.7%) and acne-like rash (13.1%). In conclusion, modified biweekly TPEx is of comparable efficacy with conventional TPEx and represents a well-tolerated regimen in R/M SCCHN patients. Further evaluation of this protocol in prospective clinical trials is warranted.

  4. Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute

    International Nuclear Information System (INIS)

    Hainsworth, John D; Thompson, Dana S; Bismayer, John A; Gian, Victor G; Merritt, William M; Whorf, Robert C; Finney, Lindsey H; Dudley, B Stephens

    2015-01-01

    This trial compared the efficacy and toxicity of standard first-line treatment with paclitaxel/carboplatin versus paclitaxel/carboplatin plus sorafenib in patients with advanced ovarian carcinoma. Patients with stage 3 or 4 epithelial ovarian cancer with residual measurable disease or elevated CA-125 levels after maximal surgical cytoreduction were randomized (1:1) to receive treatment with paclitaxel (175 mg/m 2 , 3 h infusion, day 1) and carboplatin (AUC 6.0, IV, day 1) with or without sorafenib 400 mg orally twice daily (PO BID). Patients were reevaluated for response after completing 6 weeks of treatment (two cycles); responding or stable patients received six cycles of paclitaxel/carboplatin. Patients receiving the sorafenib-containing regimen continued sorafenib (400 PO BID) for a total of 52 weeks. Eighty-five patients were randomized and received treatment.Efficacy was similar for patients receiving paclitaxel/carboplatin/sorafenib versus paclitaxel/carboplatin: overall response rates 69% versus 74%; median progression-free survival 15.4 versus 16.3 months; 2 year survival 76% versus 81%. The addition of sorafenib added substantially to the toxicity of the regimen; rash, hand–foot syndrome, mucositis, and hypertension were significantly more common in patients treated with sorafenib. The addition of sorafenib to standard paclitaxel/carboplatin did not improve efficacy and substantially increased toxicity in the first-line treatment of advanced epithelial ovarian cancer. Based on evidence from this study and other completed trials, sorafenib is unlikely to have a role in the treatment of ovarian cancer

  5. Concomitant chemoradiotherapy versus induction chemotherapy followed by chemoradiotherapy as definitive, first line treatment of squamous cell carcinoma of the head and neck. A retrospective single center analysis

    Energy Technology Data Exchange (ETDEWEB)

    Balermpas, P.; Bauer, C.; Fraunholz, I.; Ottinger, A.; Fokas, E.; Roedel, C.; Weiss, C. [Goethe University Frankfurt, Department of Radiation Therapy and Oncology, Frankfurt am Main (Germany); Wagenblast, J.; Stoever, T. [Goethe University, Department of Otorhinolaryngology, Frankfurt am Main (Germany); Seitz, O. [Goethe University, Department of Oral Maxillofacial and Plastic Facial Surgery, Frankfurt am Main (Germany)

    2014-03-15

    Despite the lack of evidence to support its implementation in the clinical practice, induction chemotherapy (IC) before chemoradiotherapy (CRT) is often used in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). We retrospectively examined the tolerability, feasibility, and clinical outcome of both concepts in a single center analysis. In all, 83 patients were treated between 2007 and 2010 with IC + CRT (n = 42) or CRT alone (n = 41). IC consisted of docetaxel, cisplatin and 5-fluorouracil (TPF), or cisplatin and 5-fluorouracil (PF). All patients were scheduled to receive 2 cycles of PF during concurrent CRT. Adverse events were assessed according to the common toxicity criteria of adverse events (CTCAE v. 3.0). Associations were tested using the χ{sup 2} test, and survival estimates were calculated according to Kaplan-Meier. The median follow-up was 30.35 months (range 2.66-61.25 months). At 2 years, the overall survival rate was significantly higher for primary CRT compared to IC + CRT group (74.8 % vs. 54 %, respectively; p = 0.041). Significantly more treatment-related overall grade 4 toxicities were documented in the IC + CRT group compared to the CRT group (42.9% vs. 9.8%; p = 0.001). Renal toxicity ≥ grade 2 occurred in 52.4 % vs. 7.3 % (p < 0.001), respectively. In all, 93 % of the patients with primary CRT compared to 71 % with IC + CRT received the planned full radiotherapy dose (p = 0.012). This is, to our knowledge, the largest retrospective study to compare IC + CRT with primary CRT. IC showed high acute toxicity, compromised the feasibility of concurrent CRT, and was associated with reduced overall survival rates compared to primary CRT. The lack of clinical benefit in conjunction with the increased toxicity does not support implementation of IC. (orig.) [German] Trotz fehlender Studienergebnisse, die den Einsatz einer Induktionschemotherapie (IC) vor einer simultanen Radiochemotherapie (RCT) in der klinischen

  6. New modalities (setting, fractionation) of radioimmunotherapy by 90Y-ibritumomab tiuxetan (90Y zevalin) in first line treatment of follicular type non Hodgkin malignant lymphomas: efficiency, toxicity and personalized dosimetry approach

    International Nuclear Information System (INIS)

    Morschhauser, F.

    2008-12-01

    Rationale: radioimmunotherapy (R.I.T.) with 90 Y-ibritumomab tiuxetan ([ 90 Y] Zevalin ) is a new treatment option for patients with relapsed/refractory non Hodgkin follicular lymphoma (F.L.). Efficacy increases when Zevalin is used earlier in the disease course. Currently, Zevalin dosage is based on weight and not dosimetry. This most likely results in a wide range of absorbed dose to critical organs and tumor, which in turn translates in unpredictable efficacy and toxicity. Optimizing R.I.T. with [ 90 Y] Zevalin will require its use as part of first-line therapy and implementation of patient-specific dosimetry methods in clinical trials. Objectives and methods: we have consecutively studied 2 new modalities of using Zevalin in first line therapy of F.L.. First, we conducted an international, randomized, phase 3 trial to evaluate the efficacy and safety of consolidation with Zevalin(15 MBq/Kg) in patients with advanced-stage F.L. achieving at least a partial response after induction immuno chemotherapy. A second approach consisted of evaluating a fractionated schedule with 2 doses of Zevalin (11.1 MBq/kg each), 9 to 13 weeks apart, as front line therapy in F.L. patients with high tumor burden. As part of this second approach, we designed a refined imaging-based (planar and 3-dimensional) dosimetry protocol to improve prediction of dose efficacy and toxicity after each dose of zevalin. Data acquisition was performed in 3 centers (Lille, Nantes and Manchester) while data treatment and specific dose calculations for major organ, tumor masses and bone marrow were centralized. Conclusion: Consolidation of first remission with 90 Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging P.F.S. by 2 years and resulting in high P.R.-to-C.R. conversion rates regardless of type of first-line induction treatment. Preliminary data show the feasibility of front line fractionated R.I.T. with Zevalin in patient

  7. Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.

    Science.gov (United States)

    Iacoboni, G; Zucca, E; Ghielmini, M; Stathis, A

    2018-05-01

    The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.

  8. OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer

    Science.gov (United States)

    Zhang, Pengfei; Hutton, David; Li, Qiu

    2018-01-01

    Objectives Erlotinib, the first generation of epidermoid growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recommended as an essential treatment in patients with non-small-cell lung cancer (NSCLC) with EGFR mutation. Although it has improved progression-free survival (PFS), overall survival (OS) was limited and erlotinib can be expensive. This cost-effectiveness analysis compares erlotinib monotherapy with gemcitabine-included doublet chemotherapy. Setting First-line treatment of Asian patients with NSCLC with EGFR mutation. Methods A Markov model was created based on the results of the ENSURE (NCT01342965) and OPTIMAL (CTONG-0802) trials which evaluated erlotinib and chemotherapy. The model simulates cancer progression and all causes of death. All medical costs were calculated from the perspective of the Chinese healthcare system. Main outcome measures The primary outcomes are costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Results The combined PFS was 11.81 months and 5.1 months for erlotinib and chemotherapy, respectively, while the OS was reversed at 24.68 months for erlotinib and 26.16 months for chemotherapy. The chemotherapy arm gained 0.13 QALYs compared with erlotinib monotherapy (1.17 QALYs vs 1.04 QALYs), while erlotinib had lower costs ($55 230 vs $77 669), resulting in an ICER of $174 808 per QALY for the chemotherapy arm, which exceeds three times the Chinese GDP per capita. The most influential factors were the health utility of PFS, the cost of erlotinib and the health utility of progressed disease. Conclusion Erlotinib monotherapy may be acceptable as a cost-effective first-line treatment for NSCLC compared with gemcitabine-based chemotherapy. The results were robust to changes in assumptions. Trial registration number NCT01342965 and CTONG-0802. PMID:29654023

  9. Real-world first-line treatment and overall survival in non-small cell lung cancer without known EGFR mutations or ALK rearrangements in US community oncology setting.

    Directory of Open Access Journals (Sweden)

    Amy P Abernethy

    Full Text Available To establish a baseline for care and overall survival (OS based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC without common actionable mutations.Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015. Patients with documented epidermal growth factor receptor (EGFR or anaplastic lymphoma kinase (ALK translocation were excluded. Anti-cancer drug therapy and overall survival were described overall, and by histology.A total of 2,014 patients with stage IV NSCLC without known EGFR or ALK genomic tumor aberrations initiated systemic anticancer therapy, 22% with squamous and 78% with nonsquamous histology. Their mean (SD age was 67 (10 years, 55% were male, and 87% had a smoking history. In nonsquamous NSCLC, carboplatin plus pemetrexed either without (25.7% or with bevacizumab (16% were the most common regimens; 26.6% of nonsquamous patients receiving induction therapy also received continuation maintenance therapy. In squamous NSCLC, carboplatin plus paclitaxel (37.6% or nab-paclitaxel (21.1% were the most commonly used regimens. Overall median OS was 9.7 months (95% CI: 9.1, 10.3, 8.5 months (95% CI: 7.4, 10.0 for squamous, and 10.0 months (95% CI: 9.4, 10.8 for nonsquamous NSCLC.The results provide context for evaluating the effect of shifting treatment patterns of NSCLC treatments on patient outcomes, and for community oncology benchmarking initiatives.

  10. Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar.

    Directory of Open Access Journals (Sweden)

    Nay Thiha

    Full Text Available WHO recommends that stavudine is phased out of antiretroviral therapy (ART programmes and replaced with tenofovir (TDF for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment.Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR to identify associated factors using log binomial regression.Of 4934 patients tested, 4324 (87% had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8 compared to 25-44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2 compared to the public sector.This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries.

  11. The Budget Impact of Including Necitumumab on the Formulary for First-Line Treatment of Metastatic Squamous Non-Small Cell Lung Cancer: U.S. Commercial Payer and Medicare Perspectives.

    Science.gov (United States)

    Bly, Christopher A; Molife, Cliff; Brown, Jacqueline; Tawney, Mahesh K; Carter, Gebra Cuyun; Cinfio, Frank N; Klein, Robert W

    2018-06-01

    Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints. To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U.S. commercial and Medicare payer perspectives. The budget impact model estimates the costs of msqNSCLC before and after adoption of Neci + GCis in hypothetical U.S. commercial and Medicare health plans over a 3-year time horizon. The eligible patient population was estimated from U.S. epidemiology statistics. Clinical data were obtained from randomized clinical trials, U.S. prescribing information, and clinical guidelines. Market share projections were based on market research data. Cost data were obtained from online sources and published literature. The incremental aggregate annual health plan, per-patient-per-year (PPPY), and per-member-per-month (PMPM) costs were estimated in 2015 U.S. dollars. One-way sensitivity analyses were conducted to assess the effect of model parameters on results. In a hypothetical 1,000,000-member commercial health plan with an estimated population of 30 msqNSCLC patients receiving first-line chemotherapy, the introduction of Neci + GCis at an initial market share of approximately 5% had an overall year 1 incremental budget impact of $88,394 ($3,177 PPPY, $0.007 PMPM), representing a 2.9% cost increase and reaching $304,079 ($10,397 PPPY, $0.025 PMPM) or a 7.4% cost increase at a market share of 14.7% in year 3. This increase in total costs was largely attributable to Neci drug costs and, in part, due to longer survival and treatment duration for patients treated with Neci+GCis. Overall, treatment costs increased by $81

  12. Budget Impact Analysis of Afatinib for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 Substitution Mutations in a U.S. Health Plan.

    Science.gov (United States)

    Graham, Jonathan; Earnshaw, Stephanie; Burslem, Kate; Lim, Jonathan

    2018-06-01

    Afatinib is 1 of 3 tyrosine kinase inhibitors approved in the United States for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions (del19) or exon 21 (L858R) substitution mutations. In clinical trials, afatinib has demonstrated improvement in progression-free survival versus standard chemotherapy and gefitinib. To analyze the impact of increases in afatinib treatment share on the cost and health outcomes in a commercial health plan in the United States. A decision model was developed to evaluate the budget impact of increases in afatinib share for the first-line treatment of patients with metastatic NSCLC with EGFR del19 or L858R substitution mutations over a 5-year time horizon. The model compared the total annual costs for a health plan with 1 million covered lives in a scenario in which afatinib share increased 5 percentage points annually to one in which all treatment shares remained constant over time. The number of patients eligible for treatment was estimated using published incidence data. Therapies included in the model were afatinib, erlotinib, gefitinib, and the chemotherapy doublet, pemetrexed in combination with cisplatin. The mean time spent by patients in progression-free and progressive disease states was based on survival data from clinical trials and a network meta-analysis. Therapy-related costs included monthly drug acquisition and administration costs and costs of managing adverse reactions. Disease management costs were also assessed in the model. Scenario analyses were performed to assess alternative scenarios of afatinib treatment share. Additionally, a one-way sensitivity analysis was performed to test the robustness of the model, given parameter uncertainty. Using the base-case parameter assumptions and a 5-percentage-point annual increase in afatinib treatment share, we estimated the total budget increases in years 1 through 5

  13. First line management in the public sector

    DEFF Research Database (Denmark)

    Voxted, Søren

    The paper will examines and discusses the results from a structured observational study, wherein 50 first-line managers from the public sector in Denmark in five areas of employment where observed. These observational studies are a key contribution in the ‘greenhouse for management’ project...... in first-line managers’ practice. Answering this question helps to illustrate and understand the degree of professionalism in terms of managers' usage of time....

  14. High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa.

    Directory of Open Access Journals (Sweden)

    Justen Manasa

    Full Text Available To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.Cross-sectional study nested within HIV treatment programme.Adult (≥ 18 years HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART regimen and with evidence of virological failure (one viral load >1000 copies/ml were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%; and stavudine, lamivudine and nevirapine (24%. Median duration of ART was 42 months (interquartile range (IQR 32-53 and median duration of antiretroviral failure was 27 months (IQR 17-40. One hundred and ninety one (86% had at least one drug resistance mutation. For 34 individuals (15%, the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR 5.70, 95% confidence interval (CI 2.60-12.49.There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.

  15. Comparative effectiveness and safety of nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin in first-line treatment of advanced squamous cell non-small cell lung cancer in a US community oncology setting

    Directory of Open Access Journals (Sweden)

    Mudad R

    2017-10-01

    Full Text Available Raja Mudad,1 Manish B Patel,2 Sandra Margunato-Debay,2 David Garofalo,3 Lincy S Lal4 1University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Hollywood, FL, USA; 2Celgene Corporation, Summit, NJ, USA; 3Cardinal Health, Dallas, TX, USA; 4University of Texas School of Public Health, Houston, TX, USA Introduction: Real-world comparative effectiveness, safety, and supportive care use of nab-paclitaxel plus carboplatin vs gemcitabine plus platinum were analyzed in patients with advanced or metastatic squamous cell non-small cell lung cancer (NSCLC.Materials and methods: Patients who received ≥ 1 cycle of first-line nab-paclitaxel plus carboplatin or gemcitabine plus platinum were identified from the Navigating Cancer database. Clinical effectiveness endpoints included overall survival (OS and time to treatment discontinuation (TTD. Other endpoints included safety and utilization of supportive care. Cox proportional hazards models were used to control for potential confounding effects of baseline characteristics.Results: In total, 193 patients were included (nab-paclitaxel plus carboplatin, n = 61; gemcitabine plus platinum, n = 132. Baseline characteristics were generally similar between the cohorts. Patients receiving nab-paclitaxel plus carboplatin had a significantly longer OS than those receiving gemcitabine plus carboplatin (median, 12.8 vs 9.0 months; P = 0.03. However, the adjusted difference was not statistically significant (adjusted HR 1.55; 95% CI, 0.99–2.42; P = 0.06. nab-Paclitaxel plus carboplatin-treated patients had significantly longer TTD than gemcitabine plus carboplatin-treated patients (median, 4.3 vs 3.5 months; P = 0.03; adjusted HR 1.39; 95% CI, 1.01–1.90; P = 0.04. Grade 3 or 4 anemia and neutropenia were significantly lower in patients treated with nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin. Nausea and neuropathy (grade not specified were significantly higher in the

  16. Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2-negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK).

    Science.gov (United States)

    Matter-Walstra, K; Ruhstaller, T; Klingbiel, D; Schwenkglenks, M; Dedes, K J

    2016-07-01

    Endocrine therapy continues to be the optimal systemic treatment for metastatic ER(+)HER2(-) breast cancer. The CDK4/6 inhibitor palbociclib combined with letrozole has recently been shown to significantly improve progression-free survival. Here we examined the cost-effectiveness of this regimen for the Swiss healthcare system. A Markov cohort simulation based on the PALOMA-1 trial (Finn et al. in Lancet Oncol 16:25-35, 2015) was used as the clinical course. Input parameters were based on summary trial data. Costs were assessed from the Swiss healthcare system perspective. Adding palbociclib to letrozole (PALLET) compared to letrozole monotherapy was estimated to cost an additional CHF342,440 and gain 1.14 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio (ICER) of CHF301,227/QALY gained. In univariate sensitivity analyses, no tested variation in key parameters resulted in an ICER below a willingness-to-pay threshold of CHF100,000/QALY. PALLET had a 0 % probability of being cost-effective in probabilistic sensitivity analyses. Lowering PALLET's price by 75 % resulted in an ICER of CHF73,995/QALY and a 73 % probability of being cost-effective. At current prices, PALLET would cost the Swiss healthcare system an additional CHF155 million/year. Palbociclib plus letrozole cannot be considered cost-effective for the first-line treatment of patients with metastatic breast cancer in the Swiss healthcare system.

  17. 'Poker' association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study

    International Nuclear Information System (INIS)

    Bruera, Gemma; Ficorella, Corrado; Ricevuto, Enrico; Santomaggio, Alessandra; Cannita, Katia; Baldi, Paola Lanfiuti; Tudini, Marianna; De Galitiis, Federica; Mancini, Maria; Marchetti, Paolo; Antonucci, Adelmo

    2010-01-01

    This phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC). Simon two-step design: delta 20% (p 0 50%, p 1 70%), power 80%, α 5%, β 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m 2 , days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m 2 plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m 2 , days 8, 22; every 4 weeks. Fifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m 2 . ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%. Poker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered. Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34

  18. No survival benefit from adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first-line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Si-wei Zhou

    Full Text Available The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR monoclonal antibodies (MAbs remains controversial in colorectal cancer (CRC. The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC through meta-analysis.Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO and European Society for Medical Oncology (ESMO were searched. Eligible studies were randomized controlled trials (RCTs which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS, progression-free survival (PFS, overall response rate (ORR and toxicities. Hazard ratios (HR and risk ratio (RR were used for the meta-analysis and were expressed with 95% confidence intervals.This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn't result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95 or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13. The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75 or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36. Patients who received combined therapy didn't have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]. Toxicities slightly increased in anti-EGFR drugs group.The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in

  19. Presence of pleural effusion is associated with a poor prognosis in patients with epidermal growth factor receptor-mutated lung cancer receiving tyrosine kinase inhibitors as first-line treatment.

    Science.gov (United States)

    Wang, Tso-Fu; Chu, Sung-Chao; Lee, Jen-Jyh; Yang, Gee-Gwo; Huang, Wei-Han; Chang, En-Ting; Low, Tissot; Wu, Yi-Feng; Kao, Ruey-Ho; Lin, Chih-Bin

    2017-08-01

    This study was conducted to evaluate the effect of clinical factors on the treatment outcomes of lung cancer patients with active epidermal growth factor receptor (EGFR) mutations treated by first-line tyrosine kinase inhibitors (TKIs). Patients of stage IIIb or IV lung adenocarcinoma harboring mutated EGFR were enrolled between March 2010 and June 2014 and followed up until December 2015. The effects of various clinical features, such as age, sex, smoking history, EGFR mutation types, TKIs used, presence of pleural effusion, metastatic sites on progression-free survival (PFS) and overall survival (OS), were analyzed retrospectively. A total of 104 patients were included in this study. Patients with pleural effusion at initial diagnosis had significantly shorter PFS and OS than those without pleural effusion (median PFS: 8.2 months vs 15.3 months, P = 0.0004; median OS: 16.3 months vs 28.2 months, P = 0.0003). Univariate analysis revealed that being male or a smoker was associated with short PFS, whereas smoking history, bony metastasis and malignant pleural effusion were associated with poor OS. Stepwise multivariate Cox regression analysis showed that the presence of pleural effusion and different TKI use were independent prognostic factors for PFS [hazard ratio [HR] = 2.50 (95% confidence interval [CI], 1.53-4.10), P = 0.0003 and HR = 0.55 (95% CI, 0.31-0.97), P = 0.0396, respectively], whereas the presence of pleural effusion and liver metastasis were associated with poor OS [HR = 2.79 (95% CI: 1.46-5.30), P = 0.0018 and HR = 2.12 (95% CI, 1.02-4.40), P = 0.0440, respectively]. The presence of pleural effusion predicts poor PFS and OS in lung adenocarcinoma patients receiving TKIs as the first-line treatment. Additional studies are warranted to elucidate the underlying mechanisms and determine novel strategies for improving the outcome of these patients. © 2017 John Wiley & Sons Australia, Ltd.

  20. Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for human epidermal growth factor receptor 2 positive locally recurrent or metastatic breast cancer: results from a Phase II, single-arm, multicenter study

    Directory of Open Access Journals (Sweden)

    Puhalla S

    2016-12-01

    Full Text Available Shannon Puhalla,1 Sharon Wilks,2 Adam M Brufsky,1 Joyce O’Shaughnessy,3 Lee S Schwartzberg,4 Erhan Berrak,5 James Song,5 Linda Vahdat6 1Department of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, 2Department of Hematology Oncology, US Oncology-Cancer Care Centers of South Texas, San Antonio, TX, 3Department of Medical Oncology, Texas Oncology-Baylor Charles A. Sammons Cancer Center US Oncology, Dallas, TX, 4Department of Hematology/Oncology, West Cancer Center, University of Tennessee Health Science Center, Memphis, TN, 5Department of Medical Affairs, Formerly of Eisai Inc., Woodcliff Lake, NJ, 6Department of Medicine, Weill Cornell Medical College, New York, NY, USA Abstract: Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor in the halichondrin class of antineoplastic drugs, is indicated for the treatment of patients with metastatic breast cancer who previously received ≥2 chemotherapy regimens in the metastatic setting. Primary data from a Phase II trial for the first-line combination of ­eribulin plus trastuzumab in human epidermal growth factor receptor 2 positive patients showed a 71% objective response rate and tolerability consistent with the known profile of these agents. Here, we present prespecified analyses of efficacy of this combination based on prior trastuzumab use. Patients received eribulin mesylate 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin [expressed as free base] intravenously on days 1 and 8 plus trastuzumab (8 mg/kg intravenously/cycle 1, then 6 mg/kg on day 1 of each 21-day cycle. Objective response rates, progression-free survival, and tolerability were assessed in patients who had and had not received prior adjuvant or neoadjuvant (neo/adjuvant trastuzumab treatment. Fifty-two patients (median age: 59.5 years received eribulin/trastuzumab for a median treatment duration of ~31 weeks; 40.4% (n=21 had been previously treated with neo/adjuvant trastuzumab prior to

  1. Quantification of viable bacteria in wastewater treatment plants by using propidium monoazide combined with quantitative PCR (PMA-qPCR).

    Science.gov (United States)

    Li, Dan; Tong, Tiezheng; Zeng, Siyu; Lin, Yiwen; Wu, Shuxu; He, Miao

    2014-02-01

    The detection of viable bacteria in wastewater treatment plants (WWTPs) is very important for public health, as WWTPs are a medium with a high potential for waterborne disease transmission. The aim of this study was to use propidium monoazide (PMA) combined with the quantitative polymerase chain reaction (PMA-qPCR) to selectively detect and quantify viable bacteria cells in full-scale WWTPs in China. PMA was added to the concentrated WWTP samples at a final concentration of 100 micromol/L and the samples were incubated in the dark for 5 min, and then lighted for 4 min prior to DNA extraction and qPCR with specific primers for Escherichia coli and Enterococci, respectively. The results showed that PMA treatment removed more than 99% of DNA from non-viable cells in all the WWTP samples, while matrices in sludge samples markedly reduced the effectiveness of PMA treatment. Compared to qPCR, PMA-qPCR results were similar and highly linearly correlated to those obtained by culture assay, indicating that DNA from non-viable cells present in WWTP samples can be eliminated by PMA treatment, and that PMA-qPCR is a reliable method for detection of viable bacteria in environmental samples. This study demonstrated that PMA-qPCR is a rapid and selective detection method for viable bacteria in WWTP samples, and that WWTPs have an obvious function in removing both viable and non-viable bacteria. The results proved that PMA-qPCR is a promising detection method that has a high potential for application as a complementary method to the standard culture-based method in the future.

  2. First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment.

    Science.gov (United States)

    Munier, Francis L; Mosimann, Pascal; Puccinelli, Francesco; Gaillard, Marie-Claire; Stathopoulos, Christina; Houghton, Susan; Bergin, Ciara; Beck-Popovic, Maja

    2017-08-01

    The introduction of intra-arterial chemotherapy (IAC) as salvage treatment has improved the prognosis for eye conservation in group D retinoblastoma. The aim of this study was to compare the outcomes of consecutive patients with advanced unilateral disease treated with either first-line intravenous chemotherapy (IVC) or first-line IAC. This is a retrospective mono-centric comparative review of consecutive patients. Sporadic unilateral retinoblastoma group D cases treated conservatively at Jules-Gonin Eye Hospital and CHUV between 1997 and 2014. From January 1997 to August 2008, IVC, combined with focal treatments, was the primary treatment approach. From September 2008 to October 2014, IAC replaced IVC as first-line therapy. 48 patients met the inclusion criteria, receiving only either IAC or IVC as primary treatment modality. Outcomes of 23 patients treated by IVC were compared with those of 25 treated by IAC; mean follow-up was 105.3 months (range 29.2-218.6) and 41.7 months (range 19.6-89.5), respectively. Treatment duration was significantly shorter in the IAC group (pchemotherapy treatment. Despite this, the results reported here imply that eyes treated with first-line IAC will have shorter treatment period, better ocular survival and visual acuity than first-line IVC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18.

    Science.gov (United States)

    Finn, Richard S; Crown, John P; Ettl, Johannes; Schmidt, Marcus; Bondarenko, Igor M; Lang, Istvan; Pinter, Tamas; Boer, Katalin; Patel, Ravindranath; Randolph, Sophia; Kim, Sindy T; Huang, Xin; Schnell, Patrick; Nadanaciva, Sashi; Bartlett, Cynthia Huang; Slamon, Dennis J

    2016-06-28

    Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6. In the randomized, open-label, phase II PALOMA-1/TRIO-18 trial, palbociclib in combination with letrozole improved progression-free survival (PFS) compared with letrozole alone as first-line treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer (20.2 months versus 10.2 months; hazard ratio (HR) = 0.488, 95 % confidence interval (CI) 0.319-0.748; one-sided p = 0.0004). Grade 3-4 neutropenia was the most common adverse event (AE) in the palbociclib + letrozole arm. We now present efficacy and safety analyses based on several specific patient and tumor characteristics, and present in detail the clinical patterns of neutropenia observed in the palbociclib + letrozole arm of the overall safety population. Postmenopausal women (n = 165) with ER+, HER2-negative, advanced breast cancer who had not received any systemic treatment for their advanced disease were randomized 1:1 to receive either palbociclib in combination with letrozole or letrozole alone. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death. The primary endpoint was PFS. We now analyze the difference in PFS for the treatment populations by subgroups, including age, histological type, history of prior neoadjuvant/adjuvant systemic treatment, and sites of distant metastasis, using the Kaplan-Meier method. HR and 95 % CI are derived from a Cox proportional hazards regression model. A clinically meaningful improvement in median PFS and clinical benefit response (CBR) rate was seen with palbociclib + letrozole in every subgroup evaluated. Grade 3-4 neutropenia was the most common AE with palbociclib + letrozole in all subgroups. Analysis of the frequency of neutropenia by grade during the first six cycles of treatment showed that there was a downward trend in Grade 3-4 neutropenia

  4. Novel Approach for Enterocutaneous Fistula Treatment with the Use of Viable Cryopreserved Placental Membrane

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    Frederick Nichols

    2016-01-01

    Full Text Available Enterocutaneous fistulas (ECF are a difficult and costly surgical complication to manage. The standard treatment of nil per os (NPO and total paraenteral nutrition (TPN is not well tolerated by patients. TPN is also known for complications associated with long term central venous catheterization and for high cost of prolonged hospital stay. We present two low output ECF cases successfully treated with viable cryopreserved placental membrane (vCPM placed into the fistula tracts. One patient is a 59-year-old male with a low output ECF from a jejunostomy tube site four weeks after the surgery. The second patient is an 87-year-old male with a low output ECF following a small bowel resection secondary to a strangulated inguinal hernia. He was evaluated on day 41 after surgery. NPO and TPN for several weeks did not resolute the ECF. The fistulae were closed postoperatively in both patients with zero output on the same day after one vCPM application. On day 3 postoperatively both patients were started on clear liquid diets and subsequently advanced to regular diets. The ECF have remained resolved for over 2 months. The use of vCPM is a novel promising approach for treatment of ECF.

  5. First-line endoscopic treatment with over-the-scope clips significantly improves the primary failure and rebleeding rates in high-risk gastrointestinal bleeding: A single-center experience with 100 cases.

    Science.gov (United States)

    Richter-Schrag, Hans-Jürgen; Glatz, Torben; Walker, Christine; Fischer, Andreas; Thimme, Robert

    2016-11-07

    To evaluate rebleeding, primary failure (PF) and mortality of patients in whom over-the-scope clips (OTSCs) were used as first-line and second-line endoscopic treatment (FLET, SLET) of upper and lower gastrointestinal bleeding (UGIB, LGIB). A retrospective analysis of a prospectively collected database identified all patients with UGIB and LGIB in a tertiary endoscopic referral center of the University of Freiburg, Germany, from 04-2012 to 05-2016 ( n = 93) who underwent FLET and SLET with OTSCs. The complete Rockall risk scores were calculated from patients with UGIB. The scores were categorized as < or ≥ 7 and were compared with the original Rockall data. Differences between FLET and SLET were calculated. Univariate and multivariate analysis were performed to evaluate the factors that influenced rebleeding after OTSC placement. Primary hemostasis and clinical success of bleeding lesions (without rebleeding) was achieved in 88/100 (88%) and 78/100 (78%), respectively. PF was significantly lower when OTSCs were applied as FLET compared to SLET (4.9% vs 23%, P = 0.008). In multivariate analysis, patients who had OTSC placement as SLET had a significantly higher rebleeding risk compared to those who had FLET (OR 5.3; P = 0.008). Patients with Rockall risk scores ≥ 7 had a significantly higher in-hospital mortality compared to those with scores < 7 (35% vs 10%, P = 0.034). No significant differences were observed in patients with scores < or ≥ 7 in rebleeding and rebleeding-associated mortality. Our data show for the first time that FLET with OTSC might be the best predictor to successfully prevent rebleeding of gastrointestinal bleeding compared to SLET. The type of treatment determines the success of primary hemostasis or primary failure.

  6. A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer: North Central Cancer Treatment Group Study N0528.

    Science.gov (United States)

    Dy, Grace K; Mandrekar, Sumithra J; Nelson, Garth D; Meyers, Jeffrey P; Adjei, Araba A; Ross, Helen J; Ansari, Rafat H; Lyss, Alan P; Stella, Philip J; Schild, Steven E; Molina, Julian R; Adjei, Alex A

    2013-01-01

    The purpose of this study was to assess the safety and efficacy of gemcitabine and carboplatin with (arm A) or without (arm B) daily oral cediranib as first-line therapy for advanced non-small-cell lung cancer. A lead-in phase to determine the tolerability of gemcitabine 1000 mg/m on days 1 and 8, and carboplatin on day 1 at area under curve 5 administered every 21 days with cediranib 45 mg once daily was followed by a 2 (A):1 (B) randomized phase II study. The primary end point was confirmed overall response rate (ORR) with 6-month progression-free survival (PFS6) rate in arm A as secondary end point. Polymorphisms in genes encoding cediranib targets and transport were correlated with treatment outcome. On the basis of the safety assessment, cediranib 30 mg daily was used in the phase II portion. A total of 58 and 29 evaluable patients were accrued to arms A and B. Patients in A experienced more grade 3+ nonhematologic adverse events, 71% versus 45% (p = 0.01). The ORR was 19% (A) versus 20% (B) (p = 1.0). PFS6 in A was 48% (95% confidence interval: 35%-62%), thus meeting the protocol-specified threshold of at least 40%. The median overall survival was 12.0 versus 9.9 months (p = 0.10). FGFR1 rs7012413, FGFR2 rs2912791, and VEGFR3 rs11748431 polymorphisms were significantly associated with decreased overall survival (hazard ratio 2.78-5.01, p = 0.0002-0.0095). The trial did not meet its primary end point of ORR but met its secondary end point of PFS6. The combination with cediranib 30 mg daily resulted in increased toxicity. Pharmacogenetic analysis revealed an association of FGFR and VEGFR variants with survival.

  7. End-of-Treatment Positron Emission Tomography After Uniform First-Line Therapy of B-Cell Posttransplant Lymphoproliferative Disorder Identifies Patients at Low Risk of Relapse in the Prospective German PTLD Registry.

    Science.gov (United States)

    Zimmermann, Heiner; Denecke, Timm; Dreyling, Martin H; Franzius, Christiane; Reinke, Petra; Subklewe, Marion; Amthauer, Holger; Kneba, Michael; Riess, Hanno; Trappe, Ralf U

    2018-05-01

    Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) is a recommended standard in the staging and response assessment of 18F-FDG-avid lymphoma. Posttransplant lymphoproliferative disorder (PTLD) can be detected by 18F-FDG-PET at diagnosis with high sensitivity and specificity. However, the role of response assessment by end-of-treatment (EOT) PET has only been addressed in small case series. We performed a retrospective, multicenter study of 37 patients with CD20-positive PTLD after solid organ transplantation treated with uniform, up-to-date, first-line protocols in the prospective German PTLD registry who had received EOT 18F-FDG-PET between 2006 and 2014. Median follow-up was 5.0 years. Any nonphysiological 18F-FDG uptake (Deauville score greater 2) was interpreted as PET-positive. By computed tomography (CT) final staging, 18 of 37 patients had a complete response, 18 had a partial response and 1 patient had stable disease. EOT PET was negative in 24 of 37 patients and positive in 13 of 37 patients. The positive predictive value of EOT PET for PTLD relapse was 38%, and the negative predictive value was 92%. Time to progression (TTP) and progression-free-survival were significantly longer in the PET negative group (P = 0.019 and P = 0.013). In the 18 patients in a partial response by CT staging, we noted highly significant differences in overall survival (P = 0.001), time to progression (P = 0.007), and progression-free survival (P < 0.001) by EOT PET. Even without baseline imaging, EOT PET in PTLD identifies patients at low risk of relapse and offers clinically relevant information, particularly in patients in a partial remission by CT staging.

  8. Sevelamer is cost effective versus calcium carbonate for the first-line treatment of hyperphosphatemia in new patients to hemodialysis: a patient-level economic evaluation of the INDEPENDENT-HD study.

    Science.gov (United States)

    Ruggeri, Matteo; Bellasi, Antonio; Cipriani, Filippo; Molony, Donald; Bell, Cynthia; Russo, Domenico; Di Iorio, Biagio

    2015-10-01

    The recent multicenter, randomized, open-label INDEPENDENT study demonstrated that sevelamer improves survival in new to hemodialysis (HD) patients compared with calcium carbonate. The objective of this study was to determine the cost-effectiveness of sevelamer versus calcium carbonate for patients new to HD, using patient-level data from the INDEPENDENT study. Cost-effectiveness analysis. Adult patients new to HD in Italy. A patient-level cost-effectiveness analysis was conducted from the perspective of the Servizio Sanitario Nazionale, Italy's national health service. The analysis was conducted for a 3-year time horizon. The cost of dialysis was excluded from the base case analysis. Sevelamer was compared to calcium carbonate. Total life years (LYs), total costs, and the incremental cost per LY gained were calculated. Bootstrapping was used to estimate confidence intervals around LYs, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve. Sevelamer was associated with a gain of 0.26 in LYs compared to calcium carbonate, over the 3-year time horizon. Total drug costs were €3,282 higher for sevelamer versus calcium carbonate, while total hospitalization costs were €2,020 lower for sevelamer versus calcium carbonate. The total incremental cost of sevelamer versus calcium carbonate was €1,262, resulting in a cost per LY gained of €4,897. The bootstrap analysis demonstrated that sevelamer was cost effective compared with calcium carbonate in 99.4 % of 10,000 bootstrap replicates, assuming a willingness-to-pay threshold of €20,000 per LY gained. Data on hospitalizations was taken from a post hoc retrospective chart review of the patients included in the INDEPENDENT study. Patient quality of life or health utility was not included in the analysis. Sevelamer is a cost-effective alternative to calcium carbonate for the first-line treatment of hyperphosphatemia in new to HD patients in Italy.

  9. Bariatric surgery: a viable treatment option for patients with severe mental illness.

    Science.gov (United States)

    Shelby, Sarah R; Labott, Susan; Stout, Rebecca A

    2015-01-01

    Although bariatric surgery has become a recognized treatment for obesity, its utility among patients with severe psychiatric disorders has not been extensively studied. A few studies have reported similar weight loss outcomes in these patients, but psychiatric status after bariatric surgery has been studied only minimally, and it is unknown if exacerbation of the mental illness affects weight loss. The aim of this study was to shed greater light on the issue of serious mental illness and bariatric surgery. Specifically, do patients with a diagnosis of schizophrenia, bipolar I, and bipolar II have poorer weight loss outcomes postbariatric surgery than the general bariatric surgery population? Also, do patients with these diagnoses experience an exacerbation of psychiatric symptoms after bariatric surgery, and if so, is the exacerbation of these disorders linked to poorer weight loss results? Midwest university medical center. A medical record review of approximately 1500 bariatric patients in a Midwest university medical center was conducted to identify those patients with diagnoses of schizophrenia, bipolar I, and bipolar II. Information was gathered on bariatric surgery outcomes and changes in psychiatric status postsurgery. Eighteen patients were identified as undergoing bariatric surgery and having a diagnosis of schizophrenia, bipolar I, or bipolar II. Weight loss in this group was significant and comparable to expected outcomes of absolute weight lost, changes in body mass index, and percentage excess weight loss for patients in the typical bariatric population. Postsurgery psychiatric status was known on 10 patients. All 10 patients experienced some exacerbation of psychiatric problems yet weight loss outcomes were still as expected. Bariatric surgery is a viable obesity treatment option for patients with schizophrenia, bipolar I, and bipolar II disorders. Symptom exacerbations occurred postsurgery, although it is not clear if these were due to the surgery or

  10. The use of super-selective mesenteric embolisation as a first-line management of acute lower gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Bryan Soh, MBBS, BBiomedSci, PGDipSurgAnat

    2017-05-01

    Conclusion: Super-selective mesenteric embolisation is a viable, safe and effective first line management for localised LGIB. Our results overall compare favourably with the published experiences of other institutions. It is now accepted first-line practice at our institution to manage localised LGIB with embolisation.

  11. Comparison of single-agent chemotherapy and targeted therapy to first-line treatment in patients aged 80 years and older with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zhang QQ

    2015-04-01

    considered primarily for patients aged 80 years and older with advanced NSCLC who cannot tolerate chemotherapy or radiotherapy. Keywords: non-small-cell lung cancer, elderly, 80 years old, first-line, chemotherapy, targeted therapy 

  12. 65Plus: open-label study of bevacizumab in combination with pemetrexed or pemetrexed/carboplatin as first-line treatment of patients with advanced or recurrent nonsquamous non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Schuette W

    2017-11-01

    Full Text Available Wolfgang Schuette,1 Claus-Peter Schneider,2,3 Walburga Engel-Riedel,4 Christian Schumann,5,6 Martin Kohlhaeufl,7 Monika Heidi Ursel Serke,8 Gert Hoeffken,9 Cornelius Kortsik,10 Martin Reck11 1Department of Internal Medicine II, Hospital Martha-Maria Halle-Doelau, Halle, 2Department of Pneumonology, Central Hospital, Bad Berka, 3Department of Internal Medicine, DRK Manniske Hospital, Bad Frankenhausen, 4Cologne Clinics, Merheim Lung Hospital, Cologne, 5Pneumonology, Department of Internal Medicine II, University Hospital Ulm, 6Clinic for Pneumology, Thoracic Oncology, Sleep, and Respiratory Critical Care, Kempten-Oberallgäu, 7Center of Pneumonology and Chest Surgery, Hospital Schillerhoehe, Gerlingen, 8Pneumonology, Lung Clinics, Hemer, 9Center of Pneumonology, Chest and Vascular Surgery, Specialty Hospital Coswig, Coswig, 10Department of Pneumonology, Catholic Hospital, Mainz, 11Department of Thoracic Oncology, Lung Clinic, Grosshansdorf, Germany Background: The aim of the study was to investigate in terms of noninferiority the efficacy and safety of a monochemotherapy regimen of pemetrexed plus bevacizumab (BevPem versus carboplatin/pemetrexed plus bevacizumab (BevCPem in elderly patients as first-line treatment for advanced metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC.Materials and methods: 65Plus was a Phase III, randomized, open-label study. In total, 253 patients received BevPem (n=119 or BevCPem (n=134. The primary outcome measure was progression-free survival. Secondary end points were overall survival, tumor response, and safety outcomes. Evaluations were performed for the whole study population and stratified according to Eastern Cooperative Oncology Group (ECOG performance status (PS.Results: Noninferiority of BevPem in comparison to BevCPem could not be demonstrated for the overall population (P=0.7864. Significant superiority of the combined treatment BevCPem was seen in patients of ECOG PS 0–1 (median

  13. Corticoide sistêmico como tratamento de primeira linha da hipertensão pulmonar secundária a síndrome POEMS Systemic corticosteroids as first-line treatment in pulmonary hypertension associated with POEMS syndrome

    Directory of Open Access Journals (Sweden)

    Samia Rached

    2009-08-01

    phenomena that involve the physiopathology of POEMS syndrome. We present the case of a 54-year-old woman diagnosed with POEMS syndrome and pulmonary hypertension, which were treated with corticosteroids as the first-line therapy. The patient presented with the classic symptoms of this syndrome: polyneuropathy (confirmed by electromyography, organomegaly, subclinical hypothyroidism and monoclonal gammopathy detected in urine, together with skin changes. Right heart catheterization revealed a mean pulmonary artery pressure of 48 mmHg, a cardiac output of 4.1 L/min and pulmonary vascular resistance of 8.05 Woods. The serum level of brain natriuretic peptide (BNP was 150 pg/mL. No other underlying disease was found during the investigation. Prednisone (1 mg/kg for three months was then initiated, with a dramatic improvement in the clinical and functional condition. Levels of thyroid hormones and urinary protein levels (as determined using electrophoresis normalized. Mean pulmonary artery pressure decreased to 26 mmHg, cardiac output decreased to 3.8 L/min, and pulmonary vascular resistance decreased to 2.89 Woods. Serum levels of BNP dropped to 8 pg/mL. Our findings suggest that corticosteroids could play a role as a first-line treatment in pulmonary hypertension accompanied by POEMS syndrome. Due to the rarity of this presentation, a multicenter registry should be developed to allow the compilation of additional data to support this practice.

  14. Maintenance based Bevacizumab versus complete stop or continuous therapy after induction therapy in first line treatment of stage IV colorectal cancer: A meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Tamburini, Emiliano; Rudnas, Britt; Santelmo, Carlotta; Drudi, Fabrizio; Gianni, Lorenzo; Nicoletti, Stefania V L; Ridolfi, Claudio; Tassinari, Davide

    2016-08-01

    In stage IV colorectal cancer, bevacizumab-based maintenance therapy, complete stop therapy and continuous therapy are considered all possible approaches after first line induction chemotherapy. However, there are no clear data about which approach is preferable. All randomized phase III trials comparing bevacizumab-based maintenance therapy (MB) with complete stop therapy (ST) or with continuous therapy (CT) were considered eligible and included into the analysis. Primary endpoint was the Time to failure strategies (TFS). Secondary endpoints were Overall Survival (OS) and Progression free survival (PFS). Meta-analysis was performed in line with the PRISMA statement. 1892 patients of five trials were included into the analysis. A significant improvement in TFS (HR 0.79; CI 95% 0.7-0.9 p=0.0005) and PFS (HR 0.56; CI 95% 0.44-0.71 p<0.00001) were observed in favour of MB versus ST. A trend, but not statistically significant, in favour of MB versus ST was also observed for OS (HR 0.88; CI 95% 0.77-1.01, p=0.08). Comparing maintenance therapy versus continuous therapy no statistically differences were observed in the outcomes evaluated (OS 12 months OR 1.1 p=0.62, OS 24 months OR 1 p=1, OS 36 months OR 0.54 p=0.3, TFS 12 months OR 0.76 p=0.65). Our meta-analysis suggests that use of MB approach increases TFS, PFS compared to ST. Although without observing any statistically advantage, it should be highlighted that MB versus ST showed a trend in favour of MB. We observed no difference between MB and CT. MB should be considered the standard regimen in patients with stage IV colorectal cancer after first line induction therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. First-line antiretroviral drug discontinuations in children.

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    Melony Fortuin-de Smidt

    Full Text Available There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.We included children (<16 years at ART initiation who initiated ≥3 antiretrovirals between 2004-2014 with ≥1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity.We included 3579 children with median follow-up duration of 41 months (IQR 14-72. At ART initiation, median age was 44 months (IQR 13-89 and median CD4 percent was 15% (IQR 9-21%. At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%, treatment failure (18%, treatment simplification (5%, drug interactions (3%, and other or unspecified reasons (18%. The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2-55.4, 1.6 (0.5-4.8, 2.0 (1.2-3.3, and 1.3 (0.6-2.8 per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively.While stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health Organization recommendation to replace stavudine with

  16. First-Line First? Trends in Thiazide Prescribing for Hypertensive Seniors

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    Morgan Steve

    2005-01-01

    Full Text Available Background Evidence of reduced cardiovascular morbidity and mortality as well as cost support thiazide diuretics as the first-line choice for treatment of hypertension. The purpose of this study was to determine the proportion of senior hypertensives that received thiazide diuretics as first-line treatment, and to determine if cardiovascular and other potentially relevant comorbidities predict the choice of first-line therapy. Methods and Findings British Columbia PharmaCare data were used to determine the cohort of seniors (residents aged 65 or older who received their first reimbursed hypertension drug during the period 1993 to 2000. These individual records were linked to medical and hospital claims data using the British Columbia Linked Health Database to find the subset that had diagnoses indicating the presence of hypertension as well as cardiovascular and other relevant comorbidities. Rates of first-line thiazide prescribing as proportion of all first-line treatment were analysed, accounting for patient age, sex, overall clinical complexity, and potentially relevant comorbidities. For the period 1993 to 2000, 82,824 seniors who had diagnoses of hypertension were identified as new users of hypertension drugs. The overall rate at which thiazides were used as first-line treatment varied from 38% among senior hypertensives without any potentially relevant comorbidity to 9% among hypertensives with previous acute myocardial infarction. The rate of first-line thiazide diuretic prescribing for patients with and without potentially relevant comorbidities increased over the study period. Women were more likely than men, and older patients were more likely than younger, to receive first-line thiazide therapy. Conclusions Findings indicate that first-line prescribing practices for hypertension are not consistent with the evidence from randomized control trials measuring morbidity and mortality. The health and financial cost of not selecting the most

  17. Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

    DEFF Research Database (Denmark)

    Desmonde, Sophie; Eboua, François T; Malateste, Karen

    2015-01-01

    BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric Ie...... post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months...... rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes....

  18. A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Bossi, P; Miceli, R; Locati, L D; Ferrari, D; Vecchio, S; Moretti, G; Denaro, N; Caponigro, F; Airoldi, M; Moro, C; Vaccher, E; Sponghini, A; Caldara, A; Rinaldi, G; Ferrau, F; Nolè, F; Lo Vullo, S; Tettamanzi, F; Hollander, L; Licitra, L

    2017-11-01

    B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53-1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38-1.20, P = 0.181). Grade ≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in

  19. Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab

    Science.gov (United States)

    Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R

    2011-01-01

    The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical success; however, many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in the activation of EGFR, HER2 and HER3 receptors as well as increased signaling through the MAP K and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared with vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increased rates of apoptosis. The work presented herein suggests that (1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and (2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing rationale

  20. Incidence and risk factors of first-line antiretroviral treatment failure among human immunodeficiency virus-infected children in Amhara regional state, Ethiopia: a retrospective follow-up study.

    Science.gov (United States)

    Sisay, Malede Mequanent; Ayele, Tadesse Awoke; Gelaw, Yalemzewod Assefa; Tsegaye, Adino Tesfahun; Gelaye, Kassahun Alemu; Melak, Melkitu Fentie

    2018-04-05

    This study aimed to assess the incidence and risk factors of treatment failure among HIV/AIDS-infected children who were on antiretroviral therapy (ART) in Amhara National Regional State, Ethiopia. A retrospective follow-up study was conducted from January 2010 to March 2016. A total of 824 children under the age of 15 who had started ART were included in the study. Data were collected from children's medical charts and ART registration logbook using a standard checklist. A Weibull regression model was used to identify the risk factors of treatment failure. Adjusted HRs (AHRs) with 95% CIs were used to declare statistical significance. The mean (±SD) age of the children was 6.4±3.6 years, with a median (IQR) follow-up of 30.5 (14.6-51.4) months. Sixty-three children (7.7%, 95% CI 5.8 to 9.5) developed treatment failure, 17 (27.0%) of whom were immunological and 46 (73.0%) were clinical failures. The incidence rate of treatment failure was 22.1/10 000 person-months. The cumulative probability of failure was 0.4, with 28 562.5 person-month observations. Lack of disclosure (AHR=4. 4, 95% CI 1.8 to 11.3), opportunistic infections during initiation of ART (AHR=2.3, 95% CI 1.3 to 4.1) and prolonged follow-up (AHR=0.06, 95% CI 0.02 to 0.18) were the main predictors of treatment failure. This study revealed that the incidence of treatment failure remains a significant public health concern in Ethiopia. Undisclosed HIV status to children, the presence of opportunistic infections during initiation of ART and prolonged follow-up were found to be the main predictors of treatment failure. Hence, early detection of treatment failure and further studies on viral monitoring need to be considered. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)-a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG

    DEFF Research Database (Denmark)

    Lindemann, K.; Christensen, R. D.; Vergote, I.

    2012-01-01

    Background: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. Patients and methods: We carried out a prospectively randomized...... of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer....

  2. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants.

    Science.gov (United States)

    Hehlmann, R; Lauseker, M; Saußele, S; Pfirrmann, M; Krause, S; Kolb, H J; Neubauer, A; Hossfeld, D K; Nerl, C; Gratwohl, A; Baerlocher, G M; Heim, D; Brümmendorf, T H; Fabarius, A; Haferlach, C; Schlegelberger, B; Müller, M C; Jeromin, S; Proetel, U; Kohlbrenner, K; Voskanyan, A; Rinaldetti, S; Seifarth, W; Spieß, B; Balleisen, L; Goebeler, M C; Hänel, M; Ho, A; Dengler, J; Falge, C; Kanz, L; Kremers, S; Burchert, A; Kneba, M; Stegelmann, F; Köhne, C A; Lindemann, H W; Waller, C F; Pfreundschuh, M; Spiekermann, K; Berdel, W E; Müller, L; Edinger, M; Mayer, J; Beelen, D W; Bentz, M; Link, H; Hertenstein, B; Fuchs, R; Wernli, M; Schlegel, F; Schlag, R; de Wit, M; Trümper, L; Hebart, H; Hahn, M; Thomalla, J; Scheid, C; Schafhausen, P; Verbeek, W; Eckart, M J; Gassmann, W; Pezzutto, A; Schenk, M; Brossart, P; Geer, T; Bildat, S; Schäfer, E; Hochhaus, A; Hasford, J

    2017-11-01

    Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

  3. Homeopathy in the Age of Antimicrobial Resistance: Is It a Viable Treatment for Upper Respiratory Tract Infections?

    Science.gov (United States)

    Fixsen, Alison

    2018-05-01

     Acute upper respiratory tract infections (URTIs) and their complications are the most frequent cause of antibiotic prescribing in primary care. With multi-resistant organisms proliferating, appropriate alternative treatments to these conditions are urgently required. Homeopathy presents one solution; however, there are many methods of homeopathic prescribing. This review of the literature considers firstly whether homeopathy offers a viable alternative therapeutic solution for acute URTIs and their complications, and secondly how such homeopathic intervention might take place.  Critical review of post 1994 clinical studies featuring homeopathic treatment of acute URTIs and their complications. Study design, treatment intervention, cohort group, measurement and outcome were considered. Discussion focused on the extent to which homeopathy is used to treat URTIs, rate of improvement and tolerability of the treatment, complications of URTIs, prophylactic and long-term effects, and the use of combination versus single homeopathic remedies.  Multiple peer-reviewed studies were found in which homeopathy had been used to treat URTIs and associated symptoms (cough, pharyngitis, tonsillitis, otitis media, acute sinusitis, etc.). Nine randomised controlled trials (RCTs) and 8 observational/cohort studies were analysed, 7 of which were paediatric studies. Seven RCTs used combination remedies with multiple constituents. Results for homeopathy treatment were positive overall, with faster resolution, reduced use of antibiotics and possible prophylactic and longer-term benefits.  Variations in size, location, cohort and outcome measures make comparisons and generalisations concerning homeopathic clinical trials for URTIs problematic. Nevertheless, study findings suggest at least equivalence between homeopathy and conventional treatment for uncomplicated URTI cases, with fewer adverse events and potentially broader therapeutic outcomes. The use of non

  4. Vinorelbine as first-line chemotherapy for metastatic breast carcinoma.

    Science.gov (United States)

    Romero, A; Rabinovich, M G; Vallejo, C T; Perez, J E; Rodriguez, R; Cuevas, M A; Machiavelli, M; Lacava, J A; Langhi, M; Romero Acuña, L

    1994-02-01

    A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.

  5. Dutasteride plus tamsulosin fixed-dose combination first-line therapy versus tamsulosin monotherapy in the treatment of benign prostatic hyperplasia: a budget impact analysis in the Greek healthcare setting.

    Science.gov (United States)

    Geitona, Maria; Karabela, Pinelopi; Katsoulis, Ioannis A; Kousoulakou, Hara; Lyberopoulou, Eleni; Bitros, Eleftherios; Xaplanteris, Loukas; Papanicolaou, Sotiria

    2014-09-26

    The purpose of this study was to explore the budget impact of dutasteride plus tamsulosin fixed-dose combination (DUT + TAM FDC) versus tamsulosin monotherapy, in the treatment of patients with benign prostatic hyperplasia (BPH) from the perspective of the Greek healthcare insurance system. A Microsoft Excel-based model was developed to estimate the financial consequences of adopting DUT + TAM FDC within the Greek healthcare setting. The model, compared six mutually exclusive health states in two alternative treatment options: current standard of care and the introduction of DUT + TAM FDC in the market. The model used clinical inputs from the CombAT study; data on resource use associated with the management of BPH in Greece were derived from expert panel, and unit cost data were derived from official reimbursement tariffs. A payer perspective was taken into account. As patient distribution data between public and private sectors are not available in Greece two scenarios were investigated, considering the whole eligible population in each scenario. A 4 year time horizon was taken into account and included treatment costs, number of transurethral resections of the prostate (TURPs) and acute urinary retention (AUR) episodes avoided. The clinical benefit from the market adoption of DUT + TAM FDC in Greece was 1,758 TURPs and 972 episodes of AUR avoided cumulatively in a four year period. The increase in total costs from the gradual introduction of DUT + TAM FDC to the Greek healthcare system ranges from €1.3 million in the first year to €5.8 million in the fourth year, for the public sector, and €1.2 million to €4.0 million, for the private sector. This represents an increase of 1.91% to 7.94% for the public sector and 1.10% 3.29% in the private sector, during the 4-year time horizon. Budget impact analysis (BIA) results indicated that the gradual introduction of DUT + TAM FDC, would increase the overall budget of the disease, however providing

  6. Treatment of produced water: is a flotation viable process?; Tratamento da agua produzida: a flotacao e um processo viavel?

    Energy Technology Data Exchange (ETDEWEB)

    Santana, Claudia Ramos; Freitas, Andrea Goncalves Bueno de; Silva, Gabriel Francisco da; Paixao, Ana Eleonora Almeida [Universidade Federal de Sergipe (UFS), Aracaju, SE (Brazil); Oliveira, Rosivania da Paixao Silva [Fundacao de Apoio a Pesquisa e Extensao de Sergipe (FAPESE), Aracaju, SE (Brazil)

    2008-07-01

    In petroleum oil wells there comes a situation when most of the oil drilled accompanies a large amount of water. This may be due to the proper conditions of the reservoir or as a consequence of the water injection in the secondary recovery processes from the well. The amount of produced water together with oil can vary to a great extent and it frequently attains to about 50% of the drilled oil. One technique employed for the treatment of industrial effluents, mainly the oily ones which is of great interest is that of flotation. This phenomenon is being extensively used for oil removal from emulsified oils in various areas, such as that of dissolved air flotation (DAF) and the induced air flotation (IAF). The conventional flotation processes consist of the following stages: bubble gas generation (normally air) from the interior of the effluent; collision between the gas bubbles and the suspended oil drops in the water; adhesion of the gas bubbles in the oil drops and ascension of aggregate oil drops/bubbles until the surface, where the oil is removed. This work seeks to contribute for the understanding of the factors which contribute for the selection of the flotation process as one of the methods most viable for the treatment of the produced water. (author)

  7. General effect of low-dose tamsulosin (0.2 mg) as a first-line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia: a systematic review and meta-analysis.

    Science.gov (United States)

    Shim, Sung Ryul; Kim, Jae Heon; Choi, Hoon; Lee, Won Jin; Kim, Hae Joon; Bae, Min Young; Hwang, Sung Dong; Kim, Khae Hwan; Bae, Jae Hyun; Yoon, Sang Jin

    2015-02-01

    In Asian countries, low-dose tamsulosin (0.2 mg) is used widely but this dose has been less popular than 0.4 mg tamsulosin or other types of alpha blockers. The aim of this study was to investigate the efficacy and safety of low-dose tamsulosin by systematic review and meta-analysis. We conducted a meta-analysis of improvements of lower urinary tract symptoms using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QOL). Relevant studies were found using MEDLINE, Embase, and the Cochrane library. Final inclusion was determined by randomized controlled trials (RCT) and performance of IPSS. A total of fourteen studies were included, with a total sample size of 2147 subjects (1044 experimental and 1103 controls). Study durations ranged from 4 to 52 weeks. The mean change of IPSS improvement from baseline for tamsulosin was -7.18 (95% CI: -7.83, -6.54). The mean change of QOL improvement from baseline was -1.34 (95% CI: -1.46, -1.22). The overall Qmax improvement from baseline was 2.32 ml/sec (95% CI: 1.95, 2.70). The mean change of PVR improvement from baseline was -11.12 ml (95% CI: -17.61, -4.64). Regarding safety, four studies did not report any adverse events while others reported that adverse events were all tolerated. Although this study did not consider placebo effect and has high IPSS baseline scores, this study clarifies that low-dose tamsulosin has generally positive effect and safety in treatment of LUTS and could be a suitable option as an initial treatment, especially for patients with low body mass index, as is typical of Asian people.

  8. Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study.

    Science.gov (United States)

    Ajani, J A; Buyse, M; Lichinitser, M; Gorbunova, V; Bodoky, G; Douillard, J Y; Cascinu, S; Heinemann, V; Zaucha, R; Carrato, A; Ferry, D; Moiseyenko, V

    2013-11-01

    The aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies. A multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses. Results (1029 treated; CS = 521/CF = 508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR) = 0.92 (two-sided 95% confidence interval (CI), 0.80-1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand-foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; Psafety profile and provides a new treatment option for patients with advanced gastric carcinoma. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. The Japanese and the American First-Line Supervisor.

    Science.gov (United States)

    Bryan, Leslie A., Jr.

    1982-01-01

    Compares the American and Japanese first-line supervisor: production statistics, supervisory style, company loyalty, management style, and communication. Also suggests what Americans might learn from the Japanese methods. (CT)

  10. Trends in CD4 cell count response to first-line antiretroviral treatment in HIV-positive patients from Asia, 2003-2013: TREAT Asia HIV Observational Database Low Intensity Transfer.

    Science.gov (United States)

    De La Mata, Nicole L; Ly, Penh S; Ng, Oon T; Nguyen, Kinh V; Merati, Tuti P; Pham, Thuy T; Lee, Man P; Choi, Jun Y; Sohn, Annette H; Law, Matthew G; Kumarasamy, Nagalingeswaran

    2017-11-01

    Antiretroviral treatment (ART) guidelines have changed over the past decade, recommending earlier initiation and more tolerable regimens. The study objective was to examine the CD4 response to ART, depending on the year of ART initiation, in HIV-positive patients in the Asia-Pacific. We included HIV-positive adult patients who initiated ART between 2003 and 2013 in our regional cohort from eight urban referral centres in seven countries within Asia. We used mixed-effects linear regression models to evaluate differences in CD4 response by year of ART initiation during 36 months of follow-up, adjusted a priori for other covariates. Overall, 16,962 patients were included. Patients initiating in 2006-9 and 2010-13 had an estimated mean CD4 cell count increase of 8 and 15 cells/µl, respectively, at any given time during the 36-month follow-up, compared to those in 2003-5. The median CD4 cell count at ART initiation also increased from 96 cells/µl in 2003-5 to 173 cells/µl in 2010-13. Our results suggest that the CD4 response to ART is modestly higher for those initiating ART in more recent years. Moreover, fewer patients are presenting with lower absolute CD4 cell counts over time. This is likely to reduce their risk of opportunistic infections and future non-AIDS defining cancers.

  11. Is Tamsulosin 0.2 mg Effective and Safe as a First-Line Treatment Compared with Other Alpha Blockers?: A Meta-Analysis and a Moderator Focused Study.

    Science.gov (United States)

    Shim, Sung Ryul; Kim, Jae Heon; Chang, In Ho; Shin, In Soo; Hwang, Sung Dong; Kim, Khae Hwan; Yoon, Sang Jin; Song, Yun Seob

    2016-03-01

    Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression. We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013. Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha-blockers as an initial treatment strategy for men with lower urinary tract symptoms.

  12. A randomized phase II trial of first-line treatment with gemcitabine, erlotinib, or gemcitabine and erlotinib in elderly patients (age ≥70 years) with stage IIIB/IV non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Peterman, Amy H; Lee, Carrie B; Moore, Dominic T; Beaumont, Jennifer L; Bradford, Daniel S; Bakri, Kamal; Taylor, Mark; Crane, Jeffrey M; Schwartz, Garry; Hensing, Thomas A; McElroy, Edwin; Niell, Harvey B; Harper, Harry D; Pal, Sridhar; Socinski, Mark A

    2011-09-01

    Single-agent gemcitabine is a standard of care for elderly patients with advanced non-small cell lung cancer, but novel therapies are needed for this patient population. We performed a noncomparative randomized phase II trial of gemcitabine, erlotinib, or the combination in elderly patients (age ≥70 years) with stage IIIB or IV non-small cell lung cancer. Patients were randomized to arms: A (gemcitabine 1200 mg/m on days 1 and 8 every 21 days), B (erlotinib 150 mg daily), or C (gemcitabine 1000 mg/m on days 1 and 8 every 21 days and erlotinib 100 mg daily). Arms B and C were considered investigational; the primary objective was 6-month progression-free survival. Between March 2006 and May 2010, 146 eligible patients received protocol therapy. The majority of the patients (82%) had stage IV disease, 64% reported adenocarcinoma histology, 90% reported current or previous tobacco use, and 28% had a performance status of 2. The 6-month progression-free survival rate observed in arms A, B, and C was 22% (95% confidence interval [CI] 11-35), 24% (95% CI 13-36), and 25% (95% CI 15-38), respectively; the median overall survival observed was 6.8 months (95% CI 4.8-8.5), 5.8 months (95% CI 3.0-8.3), and 5.6 months (95% CI 3.5-8.4), respectively. The rate of grade ≥3 hematological and nonhematological toxicity observed was similar in all three arms. The best overall health-related quality of life response did not differ between treatment arms. Erlotinib or erlotinib and gemcitabine do not warrant further investigation in an unselected elderly patient population.

  13. Dasatinib first-line: Multicentric Italian experience outside clinical trials.

    Science.gov (United States)

    Breccia, Massimo; Stagno, Fabio; Luciano, Luigiana; Abruzzese, Elisabetta; Annunziata, Mario; D'Adda, Mariella; Maggi, Alessandro; Sgherza, Nicola; Russo-Rossi, Antonella; Pregno, Patrizia; Castagnetti, Fausto; Iurlo, Alessandra; Latagliata, Roberto; Cedrone, Michele; Di Renzo, Nicola; Sorà, Federica; Rege-Cambrin, Giovanna; La Nasa, Giorgio; Scortechini, Anna Rita; Greco, Giovanna; Franceschini, Luca; Sica, Simona; Bocchia, Monica; Crugnola, Monica; Orlandi, Esther; Guarini, Attilio; Specchia, Giorgina; Rosti, Gianantonio; Saglio, Giuseppe; Alimena, Giuliana

    2016-01-01

    Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian "real-life" experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80 mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Pharmacokinetics of first-line tuberculosis drugs in tanzanian patients

    NARCIS (Netherlands)

    Tostmann, A.; Mtabho, C.M.; Semvua, H.H.; Boogaard, J. van den; Kibiki, G.S.; Boeree, M.J.; Aarnoutse, R.E.

    2013-01-01

    East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling.

  15. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. ... The progression free survival was estimated by the Kaplan-Meier method, from the date of first cycle to the date of progression or at the last consultation, and the median was 12.8 months. Trastuzumab ...

  16. Role of First-Line Noninvasive Ventilation in Non-COPD Subjects With Pneumonia.

    Science.gov (United States)

    Rialp, Gemma; Forteza, Catalina; Muñiz, Daniel; Romero, Maria

    2017-09-01

    The use of noninvasive ventilation (NIV) in non-COPD patients with pneumonia is controversial due to its high rate of failure and the potentially harmful effects when NIV fails. The purpose of the study was to evaluate outcomes of the first ventilatory treatment applied, NIV or invasive mechanical ventilation (MV), and to identify predictors of NIV failure. Historical cohort study of 159 non-COPD patients with pneumonia admitted to the ICU with ventilatory support. Subjects were divided into 2 groups: invasive MV or NIV. Univariate and multivariate analyses with demographic and clinical data were performed. Analysis of mortality was adjusted for the propensity of receiving first-line invasive MV. One hundred and thirteen subjects received first-line invasive MV and 46 received first-line NIV, of which 27 needed intubation. Hospital mortality was 35, 37 and 56%, respectively, with no significant differences among groups. In the propensity-adjusted analysis (expressed as OR [95% CI]), hospital mortality was associated with age (1.05 [1.02-1.08]), SAPS3 (1.03 [1.00-1.07]), immunosuppression (2.52 [1.02-6.27]) and NIV failure compared to first-line invasive MV (4.3 [1.33-13.94]). Compared with invasive MV, NIV failure delayed intubation (p=.004), and prolonged the length of invasive MV (p=.007) and ICU stay (p=.001). NIV failure was associated with need for vasoactive drugs (OR 7.8 [95% CI, 1.8-33.2], p=.006). In non-COPD subjects with pneumonia, first-line NIV was not associated with better outcome compared with first-line invasive MV. NIV failure was associated with longer duration of MV and hospital stay, and with increased hospital mortality. The use of vasoactive drugs predicted NIV failure. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    OpenAIRE

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    Introduction: First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods: We investigated patterns and factors associated with multi-NRTI RAMs at first-line failu...

  18. On the use of the serial dilution culture method to enumerate viable phytoplankton in natural communities of plankton subjected to ballast water treatment.

    Science.gov (United States)

    Cullen, John J; MacIntyre, Hugh L

    2016-01-01

    Discharge standards for ballast water treatment (BWT) systems are based on concentrations of living cells, for example, as determined with vital stains. Ultraviolet radiation (UV) stops the reproduction of microorganisms without killing them outright; they are living, but not viable, and ecologically as good as dead. Consequently, UV-treated discharge can be compliant with the intent of regulation while failing a live/dead test. An alternative evaluation of BWT can be proposed based on the assessment of viable, rather than living, cells in discharge water. In principle, the serial dilution culture-most probable number (SDC-MPN) method provides the appropriate measure for phytoplankton. But, the method has been criticized, particularly because it is thought that many phytoplankton species cannot be cultured. A review of the literature shows that although SDC-MPN has been used for more than 50 years-generally to identify and count phytoplankton species that cannot be preserved-its application to enumerate total viable phytoplankton seems to be new, putting past criticisms of the method in a different light. Importantly, viable cells need to grow only enough to be detected, not to be brought into sustained culture, and competition between species in a dilution tube is irrelevant as long as the winner is detectable. Thorough consideration of sources of error leads to recommendations for minimizing and quantifying uncertainties by optimizing growth conditions and conducting systematic comparisons. We conclude that with careful evaluation, SDC-MPN is potentially an effective method for assessing the viability of phytoplankton after BWT.

  19. First-line tracheal resection and primary anastomosis for postintubation tracheal stenosis.

    Science.gov (United States)

    Elsayed, H; Mostafa, A M; Soliman, S; Shoukry, T; El-Nori, A A; El-Bawab, H Y

    2016-07-01

    Introduction Tracheal stenosis following intubation is the most common indication for tracheal resection and reconstruction. Endoscopic dilation is almost always associated with recurrence. This study investigated first-line surgical resection and anastomosis performed in fit patients presenting with postintubation tracheal stenosis. Methods Between February 2011 and November 2014, a prospective study was performed involving patients who underwent first-line tracheal resection and primary anastomosis after presenting with postintubation tracheal stenosis. Results A total of 30 patients (20 male) were operated on. The median age was 23.5 years (range: 13-77 years). Seventeen patients (56.7%) had had previous endoscopic tracheal dilation, four (13.3%) had had tracheal stents inserted prior to surgery and one (3.3%) had undergone previous tracheal resection. Nineteen patients (63.3%) had had a tracheostomy. Eight patients (26.7%) had had no previous tracheal interventions. The median time of intubation in those developing tracheal stenosis was 20.5 days (range: 0-45 days). The median length of hospital stay was 10.5 days (range: 7-21 days). The success rate for anastomoses was 96.7% (29/30). One patient needed a permanent tracheostomy. The in-hospital mortality rate was 3.3%: 1 patient died from a chest infection 21 days after surgery. There was no mortality or morbidity in the group undergoing first-line surgery for de novo tracheal lesions. Conclusions First-line tracheal resection with primary anastomosis is a safe option for the treatment of tracheal stenosis following intubation and obviates the need for repeated dilations. Endoscopic dilation should be reserved for those patients with significant co-morbidities or as a temporary measure in non-equipped centres.

  20. Differences in clinical outcome between docetaxel and abiraterone acetate as the first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer patients with or without the ineligible clinical factors of the COU-AA-302 study.

    Science.gov (United States)

    Poon, Darren M C; Chan, Kuen; Lee, Siu H; Chan, Tim W; Sze, Henry; Lee, Eric K C; Lam, Daisy; Chan, Michelle F T

    2018-03-01

    This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2). The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed. The survival time was compared among four subgroups of patients: those with ineligible factors administered AA (Group Ineligible-AA) or T (Group Ineligible-T), and those without ineligible factors and administered AA (Group Eligible-AA) or T (Group Eligible-T). During the study period, we identified 115 mCRPC patients who received AA or T, among whom 29, 36, 29, and 21 patients were classified as Groups Ineligible-AA, Ineligible-T, Eligible-AA, and Eligible-T, respectively. Both Group Ineligible-AA and Group Eligible-AA had significantly longer progression-free survival (PFS) and similar overall survival (OS) as Group Ineligible-T and Group Eligible-T (Ineligible, PFS: 6.3 vs. 5.9 months, P  = 0.0234, OS: 7.8 vs. 15.7 months, P  = 0.1601; Eligible, PFS: 9.8 vs. 5.6 months, P  = 0.0437, OS: 20.5 vs. 18.2 months, P  = 0.7820). Compared to T, AA treatment resulted in longer PFS and similar OS in chemo-naïve mCRPC patients, irrespective of the presence of ineligible factors, suggesting that the initial treatment by AA may still be beneficial to those with the aforementioned ineligible factors.

  1. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu

    2014-01-01

    BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

  2. Revascularização distal com laqueação arterial (DRIL: Tratamento de eleição para a isquémia em síndrome de roubo sintomático associado a FAV Distal revascularization with interval ligation (DRIL: First line treatment for symptomatic steel syndrome associated to AVF

    Directory of Open Access Journals (Sweden)

    Pedro Amorim

    2012-03-01

    Full Text Available As complicações relacionadas com os acessos de hemodiálise (HD são o principal motivo de internamento dos doentes renais crónicos. O tratamento cirúrgico do síndrome de roubo associado a isquemia grave e crítica é mandatório e urgente. A única técnica cirúrgica que garante segurança nos resultados no que diz respeito à resolução da isquemia com preservação do acesso vascular é o DRIL. Os autores apresentam o caso de uma doente, 78 anos, com insuficiência renal crónica hipertensiva, fístula úmero-cefálica e isquemia crítica da mão esquerda. O quadro clínico, com 13 meses de evolução, foi refractário à terapêutica médica pelo que foi realizado um DRIL. Verificou-se remissão imediata da dor e melhoria progressiva das lesões tróficas dos dedos da mão com preservação do acesso. Os autores defendem a realização do DRIL como primeira linha no tratamento destes doentes.Complications related to vascular access for hemodialysis (HD are the main reason for hospitalization of chronic renal patients. Surgical treatment of steal syndrome associated with severe and critical limb ischemia is mandatory and urgent. The only surgical technique that ensures safety in the results with regard to the resolution of ischemia and preservation of vascular access is DRIL. The authors present the case of a 78 year old patient with hypertensive chronic renal failure, humeral-cephalic fistula and critical ischemia of the left hand. The clinical picture, with 13 months of evolution, was refractory to medical therapy and so a DRIL was performed. There was immediate remission of pain and progressive improvement of ulcerations of the fingers. At the same time the access for HD was preserved and early punctured. The authors advocate the implementation of DRIL as first-line treatment in these patients.

  3. A review of treatment options for Graves' disease: why total thyroidectomy is a viable option in selected patients.

    Science.gov (United States)

    Mohan, Vinuta; Lind, Robert

    2016-01-01

    Graves' disease is the most common cause of hyperthyroidism. If left untreated, patients may have multiple systemic complications such as cardiac, reproductive, and skeletal disease. Thionamides, such as methimazole and propylthiouracil, and I(131) iodine ablation are the most commonly prescribed treatment for Graves' disease. Total thyroidectomy is often overlooked for treatment and is usually only offered if the other options have failed. In our case, we discuss a patient who was admitted to our medical center with symptomatic hyperthyroidism secondary to long-standing Graves' disease. She had a history of non-compliance with medications and medical clinic follow-up. The risks and benefits of total thyroidectomy were explained and she consented to surgery. A few months after the procedure, she was biochemically and clinically euthyroid on levothyroxine. She had no further emergency room visits or admissions for uncontrolled thyroid disease. Here we review the advantages and disadvantages of the more typically prescribed treatments, thionamides and I(131)iodine ablation. We also review the importance of shared decision making and the benefits of total thyroidectomy for the management of Graves' disease. Given the improvement in surgical techniques over the past decade and a significant reduction of complications, we suggest total thyroidectomy be recommended more often for patients with Graves' disease.

  4. Influência do CD 20 na refratariedade do linfoma de Hodgkin clássico ao tratamento inicial com o esquema ABVD, no Ceará, Brasil Influence of CD 20 antigen expression in the refractoriness of classical Hodgkin lymphoma in the first line treatment with ABVD protocol in Ceará state, Brazil

    Directory of Open Access Journals (Sweden)

    Rogério Pinto Giesta

    2009-06-01

    Full Text Available INTRODUÇÃO: A significância prognóstica do marcador imunológico CD 20 no linfoma de Hodgkin clássico (LHc ainda é incerta, particularmente no que se refere à refratariedade ao tratamento inicial. OBJETIVOS: Avaliar a influência da positividade do marcador CD 20 na refratariedade do LHc ao tratamento poliquimioterápico inicial, com o esquema doxorubicina 25 mg/m², bleomicina 10 mg/m², vinblastina 6 mg/m² e dacarbazina 375 mg/m² (ABVD, no Ceará, Brasil. MATERIAL E MÉTODOS: Estudo analítico incluindo 97 pacientes com diagnóstico de LHc firmado entre janeiro de 2000 e dezembro de 2004. A análise foi realizada avaliando variáveis demográficas, clínicas e laboratoriais. RESULTADOS: Foi evidenciada uma positividade do CD 20 em 38,1% dos pacientes. Na análise bivariada, CD 20 positivo (razão de chance [RC] = 4,02; intervalo de confiança [IC] = 1,09 - 8,54; p = 0,02, a presença de sintomas B (RC = 4,02; IC = 1,18-17,51; p = 0,01 e a elevação da desidrogenase lática (mediana não-refratários 248,5 [200,5 - 389,5]; mediana refratários 356 [208,5 - 545]; p = 0,03 apresentaram relação de pior prognóstico quanto à refratariedade. Na regressão logística, o CD 20 positivo (RC ajustada = 3,6; IC = 0,99 - 13,09; p = 0,05 e a presença de sintomas B (RC ajustada = 5,41; IC = 1,16 - 25,34; p = 0,03 continuaram apresentando pior prognóstico. DISCUSSÃO: Esses dados coincidem com a literatura, em que a positividade do marcador CD 20 está relacionada com pior resposta ao tratamento com ABVD. CONCLUSÃO: Os nossos dados indicam que o tratamento com ABVD não é completamente adequado para a abordagem terapêutica inicial deste subgrupo de pacientes e novas pesquisas precisam ser realizadas no sentido de aperfeiçoar o tratamento destes pacientes.INTRODUCTION: The prognostic value of CD20 antigen expression in classical Hodgkin lymphoma (cHL is uncertain, particularly regarding the refractoriness to first-line treatment. OBJECTIVES

  5. Underreporting of side effects of standard first-line ART in the routine ...

    African Journals Online (AJOL)

    Malawi Medical Journal; 23(4): 116-118 December 2011. Side effects of standard first line in ART 116. Underreporting of side effects of standard first-line. ART in the routine setting in Blantyre, Malawi. Abstract. Introduction. In the Malawi ART programme, 92% of 250,000 patients are using the standard first-line regime of ...

  6. A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML

    DEFF Research Database (Denmark)

    Knapper, Steven; Russell, Nigel; Gilkes, Amanda

    2017-01-01

    The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activ...

  7. Incidence and predictors of severe anemia in Asian HIV-infected children using first-line antiretroviral therapy

    NARCIS (Netherlands)

    Bunupuradah, Torsak; Kariminia, Azar; Chan, Kwai-Cheng; Ramautarsing, Reshmie; Huy, Bui Vu; Han, Ning; Nallusamy, Revathy; Hansudewechakul, Rawiwan; Saphonn, Vonthanak; Sirisanthana, Virat; Chokephaibulkit, Kulkanya; Kurniati, Nia; Kumarasamy, Nagalingeswaran; Yusoff, Nik Khairulddin Nik; Razali, Kamarul; Fong, Siew Moy; Sohn, Annette H.; Lumbiganon, Pagakrong

    2013-01-01

    There are limited data on treatment-related anemia in Asian HIV-infected children. Data from Asian HIV-infected children aged <18 years on first-line highly active antiretroviral therapy (HAART) were used. Children who had pre-existing severe anemia at baseline were excluded. Anemia was graded using

  8. Clinical Observation of Icotinib Hydrochloride in First-line Therapy 
for Pulmonary Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Xinjie YANG

    2013-07-01

    Full Text Available Background and objective It has been proven that icotinib hydrochloride, as a molecule targeted drug, can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC for second-line or third-line. This research was aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the first-line therapy for pulmonary adenocarcinoma. Results Among the 56 patients, the tumor objective response rate (ORR and disease control rate (DCR was 46.4% (26/56 and 78.6% (46/56, respectively. Among the 20 patients with EGFR analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18, DCR was 94.4% (17/18 respectively. The ORR with no history of smoke. EGFR positive mutation and appearance of rash were significantly higher than those with smoker, wild type EGFR, no information about EGFR and no appearance of rash (P<0.05. The most common drug-related adverse events were mild skin rash (28.5% and diarrhea (12%. Conclusion Single agent treatment with icotinib hydrochloride is effective and tolerable in first-line therapy for pulmonary adenocarcinoma, especially with EGFR mutation.

  9. Complete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib.

    Science.gov (United States)

    Lou, Emil; Schomaker, Matthew; Wilson, Jon D; Ahrens, Mary; Dolan, Michelle; Nelson, Andrew C

    2016-08-12

    Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vismodegib, an SHH-pathway inhibitor FDA-approved in 2012 for treatment of basal cell carcinoma, has been used successfully in the setting of chemorefractory medulloblastoma, but not as a first-line therapy. In this report, we describe a sustained response of an unresectable multifocal form of adult medulloblastoma to vismodegib. Molecular analysis in this case revealed mutations in TP53 and a cytogenetic abnormality, i17q, that is prevalent and most often associated with subgroup 4 rather than the SHH-activated form of medulloblastoma. Our findings indicate that vismodegib may also block alternate, non-canonical forms of downstream SHH pathway activation. These findings provide strong impetus for further investigation of vismodegib in clinical trials in the first-line setting for pediatric and adult forms of medulloblastoma.

  10. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs

    DEFF Research Database (Denmark)

    Prahl, Julie B; Johansen, Isik S; Cohen, Arieh S

    2014-01-01

    OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6......-207 days of treatment (median 34 days) 2 h blood samples were collected from 32 patients with active tuberculosis and from three patients receiving prophylactic treatment. Plasma concentrations were determined using LC-MS/MS. Normal ranges were obtained from the literature. Clinical charts were reviewed...... failure occurred more frequently when the concentrations of isoniazid and rifampicin were both below the normal ranges (P = 0.013) and even more frequently when they were below the median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At 2 h, plasma concentrations of isoniazid...

  11. Homeopathy - A Safe, Much Less Expensive, Non-Invasive, Viable Alternative for the Treatment of Patients Suffering from Loss of Lumbar Lordosis

    Directory of Open Access Journals (Sweden)

    Saiful Haque

    2016-12-01

    Full Text Available Objectives: Loss of lumbar lordosis causing pain and curvature of the vertebral skeleton to one side is a relatively uncommon disease. To our knowledge, successful treatment of loss of lumbar lordosis with any potentized homeopathic drug diluted above Avogadro’s limit (that is, above a potency of 12C has not been documented so far. In this communication, we intend to document a relatively rare case of loss of lumbar lordosis with osteophytic lippings, disc desiccation, and protrusion, causing a narrowing of secondary spinal canal and a bilateral neural foramina, leading to vertebral column curvature with acute pain in an adolescent boy. Methods: The patient had undergone treatment with orthodox Western medicines, but did not get any relief from, or cure of, the ailment; finally, surgery was recommended. The patient’s family brought the patient to the Khuda-Bukhsh Homeopathic Benevolent Foundation where a charitable clinic is run every Friday with the active participation of four qualified homeopathic doctors. A holistic method of homeopathic treatment was adopted by taking into consideration all symptoms and selecting the proper remedy by consulting the homeopathic repertory, mainly of Kent. Results: The symptoms were effectively treated with different potencies of a single homeopathic drug, Calcarea phos. X-ray and magnetic resonance imaging (MRI supported recovery and a change in the skeletal curvature that was accompanied by removal of pain and other acute symptoms of the ailment. Conclusion: Homeopathy can be a safe, much less expensive, non-invasive, and viable alternative for the treatment of such cases.

  12. Cost-effectiveness of tenofovir instead of zidovudine for use in first-line antiretroviral therapy in settings without virological monitoring.

    Directory of Open Access Journals (Sweden)

    Viktor von Wyl

    Full Text Available BACKGROUND: The most recent World Health Organization (WHO antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV or tenofovir (TDF in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and their impact on second-line therapy. METHODS: We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base and pessimistic (extensive emergence assumptions regarding occurrence of multidrug resistance patterns were tested. RESULTS: In the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%] compared with first-line TDF users (31% [29%; 33%]. Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]. At the time of second-line initiation, a higher proportion (16% of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively. In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315

  13. Managing Viable Knowledge

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.; Vriens, D.J.

    2002-01-01

    In this paper, Beer's Viable System Model (VSM) is applied to knowledge management. Based on the VSM, domains of knowledge are identified that an organization should possess to maintain its viability. The logic of the VSM is also used to support the diagnosis, design and implementation of the

  14. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

    Science.gov (United States)

    Finn, Richard S; Crown, John P; Lang, Istvan; Boer, Katalin; Bondarenko, Igor M; Kulyk, Sergey O; Ettl, Johannes; Patel, Ravindranath; Pinter, Tamas; Schmidt, Marcus; Shparyk, Yaroslav; Thummala, Anu R; Voytko, Nataliya L; Fowst, Camilla; Huang, Xin; Kim, Sindy T; Randolph, Sophia; Slamon, Dennis J

    2015-01-01

    Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib

  15. Factors that facilitate registered nurses in their first-line nurse manager role.

    Science.gov (United States)

    Cziraki, Karen; McKey, Colleen; Peachey, Gladys; Baxter, Pamela; Flaherty, Brenda

    2014-11-01

    To determine the factors that attract and retain Registered Nurses in the first-line nurse manager role. The first-line nurse manger role is pivotal in health-care organisations. National demographics suggest that Canada will face a first-line nurse manager shortage because of retirement in the next decade. Determination of factors that attract and retain Registered Nurses will assist organisations and policy makers to employ strategies to address this shortage. The study used an exploratory, descriptive qualitative approach, consisting of semi-structured individual interviews with 11 Registered Nurses in first-line nurse manager roles. The findings revealed a discrepancy between the factors that attract and retain Registered Nurses in the first-line nurse manager role, underscored the importance of the mentor role and confirmed the challenges encountered by first-line nurse managers practicing in the current health-care environment. The first-line nurse manager role has been under studied. Further research is warranted to understand which strategies are most effective in supporting first-line nurse managers. Strategies to support nurses in the first-line nurse manager role are discussed for the individual, programme, organisation and health-care system/policy levels. © 2013 John Wiley & Sons Ltd.

  16. First-Line Cetuximab Monotherapy in KRAS/NRAS/BRAF Mutation-Negative Colorectal Cancer Patients.

    Science.gov (United States)

    Moiseyenko, Vladimir M; Moiseyenko, Fedor V; Yanus, Grigoriy A; Kuligina, Ekatherina Sh; Sokolenko, Anna P; Bizin, Ilya V; Kudriavtsev, Alexey A; Aleksakhina, Svetlana N; Volkov, Nikita M; Chubenko, Vyacheslav A; Kozyreva, Kseniya S; Kramchaninov, Mikhail M; Zhuravlev, Alexandr S; Shelekhova, Kseniya V; Pashkov, Denis V; Ivantsov, Alexandr O; Venina, Aigul R; Sokolova, Tatyana N; Preobrazhenskaya, Elena V; Mitiushkina, Natalia V; Togo, Alexandr V; Iyevleva, Aglaya G; Imyanitov, Evgeny N

    2018-06-01

    Colorectal carcinomas (CRCs) are sensitive to treatment by anti-epidermal growth factor receptor (EGFR) antibodies only if they do not carry activating mutations in down-stream EGFR targets (KRAS/NRAS/BRAF). Most clinical trials for chemo-naive CRC patients involved combination of targeted agents and chemotherapy, while single-agent cetuximab or panitumumab studies included either heavily pretreated patients or subjects who were not selected on the basis of molecular tests. We hypothesized that anti-EGFR therapy would have significant efficacy in chemo-naive patients with KRAS/NRAS/BRAF mutation-negative CRC. Nineteen patients were prospectively included in the study. Two (11%) patients experienced partial response (PR) and 11 (58%) subjects showed stable disease (SD). Median time to progression approached 6.1 months (range 1.6-15.0 months). Cetuximab efficacy did not correlate with RNA expression of EGFR and insulin-like growth factor 2 (IGF2). Only one tumor carried PIK3CA mutation, and this CRC responded to cetuximab. Exome analysis of patients with progressive disease (PD) revealed 1 CRC with high-level microsatellite instability and 1 instance of HER2 oncogene amplification; 3 of 4 remaining patients with PD had allergic reactions to cetuximab, while none of the subjects with PR or SD had this complication. Comparison with 19 retrospective KRAS/NRAS/BRAF mutation-negative patients receiving first-line fluoropyrimidines revealed no advantages or disadvantages of cetuximab therapy. Cetuximab demonstrates only modest efficacy when given as a first-line monotherapy to KRAS/NRAS/BRAF mutation-negative CRC patients. It is of question, why meticulous patient selection, which was undertaken in the current study, did not result in the improvement of outcomes of single-agent cetuximab treatment.

  17. Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer.

    Science.gov (United States)

    Romero Acuña, L; Langhi, M; Pérez, J; Romero Acuña, J; Machiavelli, M; Lacava, J; Vallejo, C; Romero, A; Fasce, H; Ortiz, E; Grasso, S; Amato, S; Rodríguez, R; Barbieri, M; Leone, B

    1999-01-01

    To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.

  18. The efficacy of levofloxacin-based triple therapy for first-line Helicobacter pylori eradication

    Directory of Open Access Journals (Sweden)

    Yusuf Aydın

    2011-06-01

    Full Text Available Standard triple therapy composed of a proton pump inhibitor, clarithromycin and amoxicillin has been widely preferred for H. pylori eradication in Turkey and World. Alternative therapies are currently under investigation because of an increase in clarithromycin resistance. The aim of this study was to evaluate the efficacy of a levoflox-acin-containing triple therapy.Materials and methods: The study was carried out in 81 H. pylori-infected patients (52 female, 29 male with nonul-cer dyspepsia. The mean age was found 46.3 ± 13.9. Treatment was indicated with lansoprazol 30 mg b.d., amoxicil-lin 1 g b.d., and levofloxacin 500 mg daily for 7 days. H. pylori status was rechecked by (14C urea breath test 6-8 weeks after the end of therapy.Results: Totally 81 patients could complete the treatment and follow-up protocol. Effectiveness was 68%. The distrib-tions of age, gender and smoking were similar between eradicated and non-eradicated groups (p > 0.05.Conclusion: Seven-day levofloxacin based triple therapy is not very effective in the first-line treatment of H. pylori in-fection. The new treatment modalities should be investigated.

  19. Coal liquefaction becomes viable

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-11-15

    In 2003 the May/June issue of CoalTrans International speculated that coal liquefaction would become viable due to falling coal prices. This has not proved the case but the sustained high oil price is sparking new interest. A survey by Energy Intelligence and Marketing Research during November 2005 revealed a growth in the number of projects under development or at the feasibility stage. The article reports projects in China, the USA, Australia, New Zealand, the Philippines and India. China is commissioning the first wave of large liquefaction plants. The key question is whether other countries, particularly the USA, will follow.

  20. Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

    Directory of Open Access Journals (Sweden)

    George G. Zhanel

    2016-01-01

    Full Text Available Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to β-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR E. coli. Resistance to fosfomycin in E. coli is rare (100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin’s in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC.

  1. Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study.

    Science.gov (United States)

    Boyd, Mark A; Amin, Janaki; Mallon, Patrick W G; Kumarasamy, Nagalingeswaran; Lombaard, Johan; Wood, Robin; Chetchotisakd, Ploenchan; Phanuphak, Praphan; Mohapi, Lerato; Azwa, Iskandar; Belloso, Waldo H; Molina, Jean-Michel; Hoy, Jennifer; Moore, Cecilia L; Emery, Sean; Cooper, David A

    2017-01-01

    Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir. Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122. Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N

  2. Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy.

    Science.gov (United States)

    Rier, Hánah N; Jager, Agnes; Sleijfer, Stefan; van Rosmalen, Joost; Kock, Marc C J M; Levin, Mark-David

    2017-02-01

    Low muscle mass (LMM) and low muscle attenuation (LMA) reflect low muscle quantity and low muscle quality, respectively. Both are associated with a poor outcome in several types of solid malignancies. This study determined the association of skeletal muscle measures with overall survival (OS) and time to next treatment (TNT). A skeletal muscle index (SMI) in cm 2 /m 2 and muscle attenuation (MA) in Hounsfield units (HU) were measured using abdominal CT-images of 166 patients before start of first-line chemotherapy for metastatic breast cancer. Low muscle mass (SMI factor for OS and TNT in metastatic breast cancer patients receiving first-line palliative chemotherapy, whereas LMM and sarcopenic obesity are not. Further research is needed to establish what impact LMA should have in daily clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

    2016-01-01

    Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2-11.8 months), and median overall survival was 21.0 months (95% CI: 20.1-21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation.

  4. Caring behaviour perceptions from nurses of their first-line nurse managers.

    Science.gov (United States)

    Peng, Xiao; Liu, Yilan; Zeng, Qingsong

    2015-12-01

    Nursing is acknowledged as being the art and science of caring. According to the theory of nursing as caring, all persons are caring but not every behaviour of a person is caring. Caring behaviours in the relationship between first-line nurse managers and Registered Nurses have been studied to a lesser extent than those that exist between patients and nurses. Caring behaviour of first-line nurse managers from the perspective of Registered Nurses is as of yet unknown. Identifying caring behaviours may be useful as a reference for first-line nurse managers caring for nurses in a way that nurses prefer. To explore first-line nurse managers' caring behaviours from the perspective of Registered Nurses in mainland China. Qualitative study, using descriptive phenomenological approach. Fifteen Registered Nurses recruited by purposive sampling method took part in in-depth interviews. Data were analysed according to Colaizzi's technique. Three themes of first-line nurse managers' caring behaviours emerged: promoting professional growth, exhibiting democratic leadership and supporting work-life balance. A better understanding of the first-line nurse managers' caring behaviours is recognised. The three kinds of behaviours have significant meaning to nurse managers. Future research is needed to describe what first-line nurse managers can do to promote nurses' professional growth, increase the influence of democratic leadership, as well as support their work-life balance. © 2015 Nordic College of Caring Science.

  5. Viable tumor in salvage neck dissections in head and neck cancer : Relation with initial treatment, change of lymph node size and human papillomavirus

    NARCIS (Netherlands)

    van den Bovenkamp, Karlijn; Dorgelo, Bart; Noordhuis, Maartje G; van der Laan, Bernard F A M; van der Vegt, Bert; Bijl, Hendrik P; Roodenburg, Jan L; van Dijk, Boukje A C; Oosting, Sjoukje F; Schuuring, Ed M D; Langendijk, Johannes A; Halmos, Gyorgy B; Plaat, Boudewijn E C

    Objectives: To identify predictive factors for the presence of viable tumor and outcome in head and neck cancer patients who undergo therapeutic salvage neck dissections. Materials and Methods: Retrospective analysis of 76 salvage neck dissections after radiotherapy alone (n = 22), radiotherapy in

  6. Economic evaluation for first-line anti-hypertensive medicines: applications for the Philippines

    Directory of Open Access Journals (Sweden)

    Geroy Lester Sam Araneta

    2012-12-01

    Full Text Available Abstract Background Medicines to control hypertension, a leading cause of morbidity and mortality, are a major component of health expenditures in the Philippines. This study aims to review economic studies for first line anti-hypertensive medical treatment without co-morbidities; and discuss practical, informational and policy implications on the use of economic evaluation in the Philippines. Methods A systematic literature review was performed using the following databases: MEDLINE, EMBASE, BIOSIS, PubMed, The Cochrane Library, Health Economics Evaluations Database (HEED and the Centre for Reviews and Dissemination – NHS NICE. Six existing economic analytical frameworks were reviewed and one framework for critical appraisal was developed. Results Out of 1336 searched articles, 12 fulfilled the inclusion criteria. The studies were summarized according to their background characteristics (year, journal, intervention and comparators, objective/study question, target audience, economic study type, study population, setting and country and source of funding/conflict of interest and technical characteristics (perspective, time horizon, methodology/modeling, search strategy for parameters, costs, effectiveness measures, discounting, assumptions and biases, results, cost-effectiveness ratio, endpoints, sensitivity analysis, generalizability, strengths and limitations, conclusions, implications and feasibility and recommendations. The studies represented different countries, perspectives and stakeholders. Conclusions Diuretics were the most cost-effective drug class for first-line treatment of hypertension without co-morbidities. Although the Philippine Health Insurance Corporation may apply the recommendations given in previous studies (i.e. to subsidize diuretics, ACE inhibitors and calcium channel blockers, it is uncertain how much public funding is justified. There is an information gap on clinical data (transition probabilities, relative risks

  7. Should laparoscopy and dye test be a first line evaluation for infertile women in southeast Nigeria?

    Science.gov (United States)

    Ikechebelu, J I; Mbamara, S U

    2011-01-01

    Laparoscopy and dye test is an important investigation in the evaluation of infertile women which has been underutilised in our practice. This review is aimed at determining whether the findings of this procedure are substantial enough to make it a first line evaluation for infertile women. A review of the laparoscopic findings in infertile women who presented for evaluation and treatment at a private fertility centre was carried out. A total of 253 day-case laparoscopy and dye test procedures were reviewed, 115 (45.0%) were done for primary infertility, 137 (54.5%) for secondary infertility and 1 (0.4%) for primary amenorrhoea and infertility. The mean period of infertility was 4.5 years with a range of 2-10 years and the women were aged between 19 and 52 years. Analysis of the result showed that 100 (39.5%) women had normal patent tubes while 153 (60.4%) had tubal pathologies like bilateral tubal occlusion in 97 (38.3%) and unilateral tubal occlusion in 56 (22.1%) women. Pelvic adhesion of varying degrees of severity was present in 108 (42.7%) women. Bilateral tubal occlusion was more common in nulliparous women and those aged between 30-39 years. One or both ovaries were normal (functional) in 189 (74.7%) women. Altogether, only 43 (17.0%) women were "normal" (had patent tubes, functional ovary and no pelvic adhesion). Additional pelvic pathology was present in 142 (56.1%) women. The commonest was uterine fibroid (leiomyomata) of various sizes in 100 (39.5%) of the women, followed by ovarian cyst in 56 (22.2%) and endometriosis in 11 (4.4%) women. Other pathologies observed include uterine abnormalities and unruptured ectopic pregnancy. Only 16 (37.2%) of the 43 "normal" women had no additional pelvic pathology. The high prevalence o tuboperitoneal factor and additional pelvic pathology in these infertile women reveal the importance of laparoscopic evaluation. We recommend the use of laparoscopy and dye test as a first line investigation in our environment to

  8. Case Reports of Idiopathic Thrombocytopenia Unresponsive to First-Line Therapies Treated With Traditional Herbal Medicines Based on Syndrome Differentiation.

    Science.gov (United States)

    Yang, Juno; Lee, Beom-Joon; Lee, Jun-Hwan

    The objective of our study is to present two cases showing the effects of traditional Korean herbal medicines based on traditional Korean medicine (TKM) for the treatment of immune thrombocytopenic purpura (ITP). One patient showed no response to treatment with steroids and an immunosuppressive agent. Moreover, liver toxicity and side effects of steroids were evident. However, after he ceased conventional treatment and started to take an herbal medicine, his liver function normalized and the steroid side effects resolved. Ultimately, he achieved complete remission. Another patient with ITP had sustained remission after steroid therapy in childhood, but extensive uterine bleeding and thrombocytopenia recurred when she was 16 years old. She was managed with steroids again for 2 years, but severe side effects occurred, and eventually she ceased taking steroids. She refused a splenectomy, and was then treated with a herbal medicine for 7 months, ultimately leading to sustained remission again. Many patients with resistance to first-line treatments tend to be reluctant to undergo a splenectomy, considered a standard second-line treatment. In conclusion, herbal medicines, based on TKM, may offer alternative treatments for persistent or chronic ITP that is resistant to existing first-line treatments. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Does first line antiretroviral therapy increase the prevalence of cardiovascular risk factors in Indian patients?: A cross sectional study.

    Science.gov (United States)

    Carey, R A B; Rupali, P; Abraham, O C; Kattula, D

    2013-01-01

    Antiretroviral therapy (ART) is associated with a myriad of metabolic complications which are potential cardiovascular risk factors. Early detection of these risk factors could help in alleviating morbidity and mortality in human immunodeficiency virus (HIV) infected patients on ART. To study the prevalence of cardiovascular risk factors in patients on a combination of nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) - the standard combination first line ART regimen used in tertiary referral center. The prevalence of cardiovascular risk factors in HIV infected subjects with stage 1t disease on standard first line ART for at least 1 year, HIV infected subjects with stage 1 disease and not on ART and HIV negative subjects was assessed. The study was a cross-sectional study design. Basic demographic data was collected and patients were examined for anthropometric data and blood was collected for analysis of blood glucose, serum lipids, and fasting insulin levels. Chi-square test was used to calculate significance. Statistical Package for Social Sciences (SPSS) software version 16.0 was used for data analysis. The prevalence of hypercholesterolemia and hypertriglyceridemia was higher in the patients on ART when compared to patients not on ART (PART and those not on ART. First line ART is associated with increased prevalence of dyslipidemia. Early detection and treatment of dyslipidemia should help in reducing the cardiovascular morbidity in patients on ART.

  10. The Ceremonial Side of Training--Of What Value to First-Line Supervisors?

    Science.gov (United States)

    Adams, Fred P.

    1976-01-01

    A case study to determine whether the recognition of being selected for a training program and the satisfactory completion of it result in increased job satisfaction using 56 first-line supervisors from a textile company. (WL)

  11. Resilience and Work-life Balance in First-line Nurse Manager

    OpenAIRE

    Kim, Miyoung; Windsor, Carol

    2015-01-01

    Purpose: The aim of this study was to explore how first-line nurse managers constructed the meaning of resilience and its relationship to work-life balance for nurses in Korea. Methods: Participants were 20 first-line nurse managers working in six university hospitals. Data were collected through in-depth interviews from December 2011 to August 2012, and analyzed using Strauss and Corbin's grounded theory method. Results: Analysis revealed that participants perceived work-life balance a...

  12. Rapid Quantification of Viable Campylobacter Bacteria on Chicken Carcasses, Using Real-Time PCR and Propidium Monoazide Treatment, as a Tool for Quantitative Risk Assessment

    DEFF Research Database (Denmark)

    Josefsen, Mathilde Hartmann; Löfström, Charlotta; Hansen, Tina Beck

    2010-01-01

    A number of intervention strategies against Campylobacter contaminated poultry focus on post-slaughter reduction of the number of cells, emphasizing the need for rapid and reliable quantitative detection of only viable Campylobacter. We present a new and rapid quantitative approach for enumeration...... method does not detect DNA from dead Campylobacter, but recognises the infectious potential of the VBNC state, and is thereby able to assess the effect of control strategies, and provide trustworthy data for risk assessment....

  13. Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

    Science.gov (United States)

    Saiz, A; Mora, S; Blanco, J

    2015-05-01

    Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Economic evaluation of first-line adjuvant chemotherapies for resectable gastric cancer patients in China.

    Science.gov (United States)

    Tan, Chongqing; Peng, Liubao; Zeng, Xiaohui; Li, Jianhe; Wan, Xiaomin; Chen, Gannong; Yi, Lidan; Luo, Xia; Zhao, Ziying

    2013-01-01

    First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.

  15. Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Snyder, Matthew; Bottiglieri, Sal; Almhanna, Khaldoun

    2018-01-01

    Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy. However, many significant questions remain as to which agent reflects best practice. Our review aimed to elucidate the benefit of adding bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer based on primary tumor location and a variety of other disease- and patient-related factors, addressing the paucity of evidence that currently exists in this area and contributing to current literature and clinical practices. The primary endpoints of the study were first Progression-Free Survival (PFS) and Overall Survival (OS). Secondary endpoints included best response to first- and second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS, cost of therapy, and an assessment of other patient- and disease-related factors affecting PFS and OS. While there were trends towards improved OS in patients with left-sided primary tumors (n=57) compared to those with right-sided disease (n=23), there were no significant differences between the two groups in either primary endpoint. While no differences were found for patients with left- or right- sided tumors stratified by add-on agent, these analyses were limited by the small number of patients receiving cetuximab with first-line therapy (n=4). However, the bevacizumab cohort (n=76) was sizable enough to provide ample data and produce clinically relevant results. Add-on therapy with bevacizumab in our study achieved impressive survival outcomes in both left-sided (median first PFS = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21

  16. Short-course thrombolysis as the first line of therapy for cardiac valve thrombosis.

    Science.gov (United States)

    Manteiga, R; Carlos Souto, J; Altès, A; Mateo, J; Arís, A; Dominguez, J M; Borrás, X; Carreras, F; Fontcuberta, J

    1998-04-01

    To retrospectively evaluate the clinical and echocardiographic criteria of thrombolytic therapy for mechanical heart valve thrombosis. Nineteen consecutive patients with 22 instances of prosthetic heart valve thrombosis (14 mitral, 2 aortic, 3 tricuspid, and 3 pulmonary) were treated with short-course thrombolytic therapy as first option of treatment in absence of contraindications. The thrombolytic therapy protocol consisted of streptokinase (1,500,000 IU in 90 minutes) (n = 18) in one (n = 7) or two (n = 11) cycles or recombinant tissue-type plasminogen activator (100 mg in 90 minutes) (n = 4). Overall success was seen in 82%, immediate complete success in 59%, and partial success in 23%. Six patients without total response to thrombolytic therapy underwent surgery, and pannus was observed in 83%. Six patients showed complications: allergy, stroke, transient ischemic attack, coronary embolism, minor bleeding, and one death. At diagnosis, 10 patients evidenced atrial thrombus by transesophageal echocardiography, 3 of whom experienced peripheral embolism during thrombolysis. Four episodes of rethrombosis were observed (16%). The survivorship was 84% with a mean follow-up of 42.6 months. A short-course of thrombolytic therapy may be considered first-line therapy for prosthetic heart valve thrombosis. The risk of peripheral embolism may be evaluated for the presence of atrial thrombus by transesophageal echocardiography at diagnosis.

  17. First-Line Nursing Home Managers in Sweden and their Views on Leadership and Palliative Care.

    Science.gov (United States)

    Håkanson, Cecilia; Cronfalk, Berit Seiger; Henriksen, Eva; Norberg, Astrid; Ternestedt, Britt-Marie; Sandberg, Jonas

    2014-01-01

    The aim of this study was to investigate first-line nursing home managers' views on their leadership and related to that, palliative care. Previous research reveals insufficient palliation, and a number of barriers towards implementation of palliative care in nursing homes. Among those barriers are issues related to leadership quality. First-line managers play a pivotal role, as they influence working conditions and quality of care. Nine first-line managers, from different nursing homes in Sweden participated in the study. Semi-structured interviews were conducted and analysed using qualitative descriptive content analysis. In the results, two categories were identified: embracing the role of leader and being a victim of circumstances, illuminating how the first-line managers handle expectations and challenges linked to the leadership role and responsibility for palliative care. The results reveal views corresponding to committed leaders, acting upon demands and expectations, but also to leaders appearing to have resigned from the leadership role, and who express powerlessness with little possibility to influence care. The first line managers reported their own limited knowledge about palliative care to limit their possibilities of taking full leadership responsibility for implementing palliative care principles in their nursing homes. The study stresses that for the provision of high quality palliative care in nursing homes, first-line managers need to be knowledgeable about palliative care, and they need supportive organizations with clear expectations and goals about palliative care. Future action and learning oriented research projects for the implementation of palliative care principles, in which first line managers actively participate, are suggested.

  18. Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

    Science.gov (United States)

    Karamchand, Sumanth; Leisegang, Rory; Schomaker, Michael; Maartens, Gary; Walters, Lourens; Hislop, Michael; Dave, Joel A; Levitt, Naomi S; Cohen, Karen

    2016-03-01

    Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.

  19. Methotrexate as a first-line corticosteroid-sparing therapy in a cohort of uveitis and scleritis.

    Science.gov (United States)

    Kaplan-Messas, Audrey; Barkana, Yaniv; Avni, Isaac; Neumann, Ron

    2003-06-01

    To evaluate the clinical experience with methotrexate as a first-line corticosteroid-sparing drug in patients with resistant ocular inflammation. We retrospectively studied 39 consecutive patients with uveitis (n = 36) or scleritis (n = 3) who were treated with methotrexate following inadequate control with corticosteroids lasting five years. Criteria for initiating treatment with methotrexate and defining outcome were strictly defined. The cohort included 21 females and 18 males, all Caucasians, with a mean age of 26.6 years (range: 3-73 years). Patients were followed up for 21.5 +/- 12.6 months. Treatment was discontinued due to side effects in 10 patients (26%). Of the remaining 29 patients, full or partial control of inflammation was achieved in 23 (79%). Response to treatment was observed after a mean of 2.4 +/- 0.8 months. Ten patients were fully controlled and discontinued methotrexate therapy after a mean of 20.9 +/- 9.2 months, with no recurrence of inflammation. Use of topical and systemic corticosteroids was markedly reduced in responsive patients. Methotrexate is recommended as a first-line adjunct to or replacement of systemic corticosteroids in the treatment of ocular inflammation.

  20. Ifosfamide and mitoxantrone as first-line chemotherapy for metastatic breast cancer.

    Science.gov (United States)

    Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Bianco, A; Lacava, J A; Rodriguez, R; Cuevas, M A

    1993-03-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation.

  1. Influence of wellness education on first-line icotinib hydrochloride patients with stage IV non-small cell lung cancer and their family caregivers.

    Science.gov (United States)

    Yanwei, Li; Minghui, Fang; Manman, Quan; Zhuchun, Yan; Dongying, Liu; Zhanyu, Pan

    2018-04-11

    This study aims to examine the effects of wellness education (WE) intervention on the behavioral change, psychological status, performance status on patients with stage IV non-small cell lung cancer (NSCLC) undergoing icotinib hydrochloride treatment and their relationships with family caregivers. We conducted an intervention study involving 126 individuals with confirmed activating epidermal growth factor receptor mutation-positive stage IV NSCLC who received icotinib hydrochloride as first-line therapy between January 2014 and January 2016; their caregivers were also included in the study. For a period of 12 weeks, participants were randomly assigned into WE and control groups. The patients and family members in the WE group were provided with WE information about treatment, diet, social needs, rehabilitation, physical/mental health education, communication strategies, and patient care advice at least 3 times per week during treatment. Qualitative feedback of the participants was recorded during the intervention. Food Composition Database, the Family Environment Scale, patients/caregivers quality-of-life (Functional Assessment of Cancer Therapy-Lung/Caregiver Quality of Life Index-Cancer Scale), and Hospital Anxiety and Depression Scale (HADS) were measured at baseline and for 12 weeks. Data were analyzed to compare the different outcomes. Of the 126 caregivers (64 WE and 62 control), 120 completed the study. We observed significant differences between the WE group and control group with respect to low daily calorie intake (31.0% vs 77.4%, p 0.05). After 12 weeks, WE intervention had improved scores on Functional Assessment of Cancer Therapy-Lung-EWB and Caregiver Quality of Life Index-Cancer Scale adaptation. In addition, the patients also showed improvements in HADS. WE interventions in patients with stage IV NSCLC undergoing icotinib hydrochloride treatment and their family resulted in strong intentions to engage in health-promoting behaviors related to

  2. Economic Outcomes of First-Line Regimen Switching Among Stable Patients with HIV.

    Science.gov (United States)

    Rosenblatt, Lisa; Buikema, Ami R; Seare, Jerry; Bengtson, Lindsay G S; Johnson, Jonathan; Cao, Feng; Villasis-Keever, Angelina

    2017-07-01

    Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months. Those with evidence of pregnancy or HIV-2 were excluded. Patients who underwent an ART change were assigned to a switcher cohort; a nonswitcher cohort was then generated by matching up to 20 nonswitchers for each switcher, with replacement. The index date was the date of the first ART change for switchers and was the claim date closest to the corresponding switcher's switch date for nonswitchers. Patient characteristics at baseline and post-index annualized health care utilization and costs were analyzed descriptively and with multivariable models. Analyses were performed in the full population and among patients designated as virologically stable (had undetectable viral ribonucleic acid [RNA] for 90 days pre-index) and virologically and clinically stable (had undetectable viral RNA and no apparent clinical reason for switching ART). The study population consisted of 6,983 individuals, which included 927 switchers (168 virologically stable; 55 virologically+clinically stable), who were matched with replacement with 18,511 nonswitcher comparators. The switcher cohort was 88.8% male (mean age 43.8 years). Mean preindex and follow-up treatment durations for switchers and nonswitchers were 1.8 years and 1.5 years, respectively; demographic characteristics, pre-index treatment duration, and follow-up duration were similar between cohorts. Significantly more

  3. A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis

    Directory of Open Access Journals (Sweden)

    Rachita Dhurat

    2018-01-01

    Full Text Available The Conidiobolus coronatus-related rhinoentomophthoromycosis in immunocompetent and immunocompromised (HIV negative individuals has been treated successfully with antifungal drugs. However, C. coronatus infections in first-line antiretroviral therapy (ART-resistant (HIV infected individuals particularly with rhinoentomophthoromycosis have not been reported previously. Here, we describe a case of itraconazole non-responding rhinoentomophthoromycosis in an HIV-infected patient with first-line antiretroviral (ART drug resistance which was successfully managed through systematic diagnostic and therapeutic approaches in dermatologic setting. A 32-year-old HIV-1-infected man presented with painless swelling, nasal redness and respiratory difficulty. The patient was receiving first-line ART and had a history of traumatic injury before the onset of nasopharyngeal manifestations. The patient's previous history included oral candidiasis and pulmonary tuberculosis.

  4. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Shen YW

    2016-02-01

    Full Text Available Yan-Wei Shen,* Xiao-Man Zhang,* Shu-Ting Li, Meng Lv, Jiao Yang, Fan Wang, Zhe-Ling Chen, Bi-Yuan Wang, Pan Li, Ling Chen, Jin Yang Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Background and objective: Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation.Patients and methods: Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1.Results: Among the 35 patients, the tumor objective response rate (ORR and disease control rate were 62.9% (22/35 and 88.6% (31/35, respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months, and median overall survival was 21.0 months (95% CI: 20.1–21.9 months. The most common drug-related toxicities were rashes (eleven patients and diarrhea (nine patients, but these were generally manageable and reversible.Conclusion: Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. Keywords: lung neoplasms, icotinib hydrochloride, first-line treatment

  5. Review of first line supervisory positions in nuclear power plants - Phase II

    Energy Technology Data Exchange (ETDEWEB)

    Mackenzie, C W; Huntley, M [Hickling Corp., Ottawa, ON (Canada)

    1995-10-01

    This report provides an overview of first line supervisory activities at Ontario Hydro nuclear generating stations (Pickering `A` and Bruce `B`) and the Point Lepreau nuclear generating station in New Brunswick. Activity profiles describing the range of first line supervisory roles and responsibilities for nuclear operators have been developed from survey data and flowcharting methods. These activity profiles have then been compared with formal job responsibilities as identified in job descriptions, supervisory training provided and assessment criteria used to evaluate supervisors. Finally, this report relates the findings of supervisory practices in the group under study with the findings in the current literature relating to supervisory functioning. (author). 32 tabs., 2 figs.

  6. Review of first line supervisory positions in nuclear power plants - Phase II

    International Nuclear Information System (INIS)

    Mackenzie, C.W.; Huntley, M.

    1995-10-01

    This report provides an overview of first line supervisory activities at Ontario Hydro nuclear generating stations (Pickering 'A' and Bruce 'B') and the Point Lepreau nuclear generating station in New Brunswick. Activity profiles describing the range of first line supervisory roles and responsibilities for nuclear operators have been developed from survey data and flowcharting methods. These activity profiles have then been compared with formal job responsibilities as identified in job descriptions, supervisory training provided and assessment criteria used to evaluate supervisors. Finally, this report relates the findings of supervisory practices in the group under study with the findings in the current literature relating to supervisory functioning. (author). 32 tabs., 2 figs

  7. PCR-based detection of bacterial DNA after antimicrobial treatment is indicative of persistent, viable bacteria in the chinchilla model of otitis media.

    Science.gov (United States)

    Post, J C; Aul, J J; White, G J; Wadowsky, R M; Zavoral, T; Tabari, R; Kerber, B; Doyle, W J; Ehrlich, G D

    1996-01-01

    Bacterial deoxyribonucleic acid (DNA) has been previously detected by polymerase chain reactions (PCR) in a significant percentage of culturally-sterile pediatric middle-ear effusions. The current study was designed to determine whether this represents the existence of viable bacteria or the persistence of residual DNA in the middle-ear cleft. The middle-ear cavities of two sets of chinchillas were inoculated with either: 1) 100 colony-forming units (CFU) of live Haemophilus influenzae, 2.2 x 10(6) CFU of pasteurized Moraxella catarrhalis, and 1000 ng of DNA (>10(8) genomic equivalents) from Streptococcus pneumoniae; or 2) 100 CFU of live S pneumoniae, 2.2 x 10(6) CFU of pasteurized M catarrhalis and 1000 ng of purified DNA from H influenzae. Animals were treated with ampicillin for 5 days beginning on day 3. A single-point longitudinal study design was used for sampling to eliminate the possibility of contamination. No DNA was detectable from the heat-killed bacteria or the purified DNA after day 3. However, DNA from the live bacteria persisted through day 21, even though all specimens were culture-negative following the initiation of antimicrobial therapy. These findings indicate that purified DNA and DNA from intact but nonviable bacteria do not persist in the middle-ear cleft in the presence of an effusion, even following high copy inoculation. In contrast, antibiotic-treated bacteria persist in some viable state for weeks as evidenced by the differential ability of the PCR-based assay systems to detect the live bacteria, but not detect the heat-killed organisms.

  8. Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy.

    Science.gov (United States)

    Zhang, Wei; Chen, Qi; Liang, Xiao; Liu, Wenzhong; Xiao, Shudong; Graham, David Y; Lu, Hong

    2015-11-01

    To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy. Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial. Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (e.g., susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group. These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. NCT02175901. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda

    Directory of Open Access Journals (Sweden)

    Sempa Joseph

    2012-09-01

    Full Text Available Abstract Background Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART at CD4+ T cell (CD4 count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250–350 cell/μl (early versus Methods Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/μl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/μl. All costs and benefits were discounted at 3% annually. Results Treatment delay varied from 6–18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33–3.10 disability adjusted life years (DALY’s per patient. Lifetime treatment costs were $4,300–$5,248 for early initiation and $3,940–$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260–$270. Conclusions In HIV-positive patients presenting with CD4 count between 250-350 cells/μl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.

  10. Ifosfamide and vinorelbine as first-line chemotherapy for metastatic breast cancer.

    Science.gov (United States)

    Leone, B A; Vallejo, C T; Romero, A O; Perez, J E; Cuevas, M A; Lacava, J A; Sabatini, C L; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Salvadori, M A; Acuña, L A; Acuña, J M; Langhi, M J; Amato, S; Machiavelli, M R

    1996-11-01

    To evaluate the efficacy and toxicity of the combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in metastatic breast cancer (MBC). Between August 1993 and August 1995, 45 patients with untreated MBC received a regimen that consisted of IFX 2 g/m2 by 1-hour intravenous (i.v.) infusion on days 1 to 3, mesna 400 mg/m2 by i.v. bolus at hours 0 and 4 and 800 mg/m2 orally at hour 8 on days 1 to 3, and VNB 35 mg/m2 by 20-minute i.v. infusion on days 1 and 15. Courses were repeated every 28 days. During the first course only, half-dose VNB (17.5 mg/m2) was administered on days 8 and 22. The median age was 53 years and 30 patients (67%) were postmenopausal. Dominant sites of disease were soft tissue in nine patients, bone in seven, and visceral in 29. Objective responses (ORs) were recorded in 25 of 43 assessable patients (58%; 95% confidence interval, 43% to 73%). Complete remissions (CRs) occurred in six patients (14%) and partial remissions (PRs) in 19 (44%). No change (NC) was recorded in 10 patients (23%) and progressive disease (PD) in eight patients (19%). The median time to treatment failure was 12 months and the median survival duration 19 months. Myelosuppression was the limiting toxicity, mainly leukopenia in 32 patients (74%). In contrast, anemia and thrombocytopenia were mild. Other significant toxicities included peripheral neuropathy in nine patients (21%), constipation in 15 (35%), and myalgias in 11 (26%). IFX/VNB is an active combination against MBC with moderate toxicity and deserves further evaluation.

  11. Ifosfamide and vinorelbine as first-line chemotherapy for advanced non-small cell lung carcinoma.

    Science.gov (United States)

    Vallejo, C; Romero, A; Perez, J; Cuevas, M; Lacava, J; Sabatini, C; Dominguez, M; Rodriguez, R; Barbieri, M; Romero Acuña, L; Romero Acuña, J; Langhi, M; Amato, S; Salvadori, M; Ortiz, E; Machiavelli, M; Leone, B

    1996-12-01

    We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

  12. First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Ruiz-Morales, Jose Manuel; Swierkowski, Marcin; Wells, J Connor

    2016-01-01

    BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. PATIENTS AND METHODS: We used the International mR...

  13. Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

    Science.gov (United States)

    Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

    2012-04-01

    We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

  14. Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial.

    Directory of Open Access Journals (Sweden)

    Shernan G Holtan

    Full Text Available Metastatic carcinoma of unknown primary (CUP has a very poor prognosis, and no standard first-line therapy currently exists. Here, we report the results of a phase II study utilizing a combination of gemcitabine and irinotecan as first-line therapy. Treatment was with gemcitabine 1000 mg/m(2 and irinotecan 75 mg/m(2 weekly times four on a six week cycle (Cohort I. Due to excessive toxicity, the dose and schedule were modified as follows: gemcitabine 750 mg/m(2 and irinotecan 75 mg/m(2 given weekly times three on a four week cycle (Cohort II. The primary endpoint was the confirmed response rate (CR + PR. Secondary endpoints consisted of adverse events based upon the presence or absence of the UDP glucuronosyltransferase 1 family, polypeptide A1*28 (UGT1A1*28 polymorphism, time to progression, and overall survival. Thirty-one patients were enrolled with a median age of 63 (range: 38-94, and 26 patients were evaluable for efficacy. Significant toxicity was observed in Cohort 1, characterized by 50% (7/14 patients experiencing a grade 4+ adverse event, but not in cohort II. The confirmed response rate including patients from both cohorts was 12% (95% CI: 2-30%, which did not meet the criteria for continued enrollment. Overall median survival was 7.2 months (95% CI: 4.0 to 11.6 for the entire cohort but notably longer in cohort II than in cohort I (9.3 months (95% CI: 4.1 to 12.1 versus 4.0 months (95% CI: 2.2 to 15.6. Gemcitabine and irinotecan is not an active combination when used as first line therapy in patients with metastatic carcinoma of unknown primary. Efforts into developing novel diagnostic and therapeutic approaches remain important for improving the outlook for this heterogeneous group of patients.ClinicalTrials.gov NCT00066781.

  15. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick C K; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher K C; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥ 2 TAMs; or M184V+≥ 1 TAM. Virological suppression was defined as viral load (VL) failure and (2) factors associated with virological suppression after 12 months on second-line. A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], pfailure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

  16. adverse events to first line anti-tuberculosis drugs in patients co

    African Journals Online (AJOL)

    status on the risk of developing adverse events to first line anti-TB therapy. Method: The ... with TB-HIV infection were allocated to a second group. ... and negative responses were entered into individual .... Extra-pulmonary TB (yes versus no).

  17. Factors contributing to managerial competence of first-line nurse managers: A systematic review.

    Science.gov (United States)

    Gunawan, Joko; Aungsuroch, Yupin; Fisher, Mary L

    2018-02-01

    To determine the factors contributing to managerial competence of first-line nurse managers. Understanding factors affecting managerial competence of nurse managers remains important to increase the performance of organizations; however, there is sparse research examining factors that influence managerial competence of first-line nurse managers. Systematic review. The search strategy was conducted from April to July 2017 that included 6 electronic databases: Science Direct, PROQUEST Dissertations and Theses, MEDLINE, CINAHL, EMBASE, and Google Scholar for the years 2000 to 2017 with full text in English. Quantitative and qualitative research papers that examined relationships among managerial competence and antecedent factors were included. Quality assessment, data extractions, and analysis were completed on all included studies. Content analysis was used to categorize factors into themes. Eighteen influencing factors were examined and categorized into 3 themes-organizational factors, characteristics and personality traits of individual managers, and role factors. Findings suggest that managerial competence of first-line nurse managers is multifactorial. Further research is needed to develop strategies to develop managerial competence of first-line nurse managers. © 2017 John Wiley & Sons Australia, Ltd.

  18. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

    NARCIS (Netherlands)

    Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; Heuvel, M. van den; Ciuleanu, T.E.; Badin, F.; Ready, N.; Hiltermann, T.J.N.; Nair, S.; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J.M.; Rodriguez-Abreu, D.; Borghaei, H.; umenschein GR, J.r. Bl; Villaruz, L.C.; Havel, L.; Krejci, J.; rral Jaime, J. Co; Chang, H.; Geese, W.J.; Bhagavatheeswaran, P.; Chen, A.C.; Socinski, M.A.

    2017-01-01

    BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  19. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Carbone, D. P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; van den Heuvel, M. M.; Ciuleanu, T. -E.; Badin, F.; Ready, N.; Hiltermann, T. J. N.; Nair, S; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J. M.; Rodriguez-Abreu, D.; Borghaei, H.; Blumenschein, G. R.; Villaruz, L. C.; Havel, L.; Krejci, J.; Corral Jaime, J.; Chang, C. -H.; Geese, W. J.; Bhagavatheeswaran, P.; Chen, Alexander C.; Socinski, M. A.

    2017-01-01

    BACKGROUND Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  20. Efficacy of S-1 plus nedaplatin compared to standard second-line chemotherapy in EGFR-negative lung adenocarcinoma after failure of first-line chemotherapy.

    Science.gov (United States)

    Tang, Yu; Wang, Wei; Teng, Xiu-Zhi; Shi, Lin

    2014-09-01

    For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

  1. Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients.

    Science.gov (United States)

    Cui, Shaohua; Zhao, Yizhuo; Dong, Lili; Gu, Aiqin; Xiong, Liwen; Qian, Jialin; Zhang, Wei; Niu, Yanjie; Pan, Feng; Jiang, Liyan

    2016-06-01

    Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving

  3. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.

    Science.gov (United States)

    Hortobagyi, Gabriel N; Stemmer, Salomon M; Burris, Howard A; Yap, Yoon-Sim; Sonke, Gabe S; Paluch-Shimon, Shani; Campone, Mario; Blackwell, Kimberly L; André, Fabrice; Winer, Eric P; Janni, Wolfgang; Verma, Sunil; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Petrakova, Katarina; Hart, Lowell L; Villanueva, Cristian; Chan, Arlene; Jakobsen, Erik; Nusch, Arnd; Burdaeva, Olga; Grischke, Eva-Maria; Alba, Emilio; Wist, Erik; Marschner, Norbert; Favret, Anne M; Yardley, Denise; Bachelot, Thomas; Tseng, Ling-Ming; Blau, Sibel; Xuan, Fengjuan; Souami, Farida; Miller, Michelle; Germa, Caroline; Hirawat, Samit; O'Shaughnessy, Joyce

    2016-11-03

    The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10 -5 . The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10 -6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2

  4. PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy.

    Science.gov (United States)

    Vincenzi, Bruno; Santini, Daniele; Schiavon, Gaia; Frezza, Anna Maria; Silletta, Marianna; Crucitti, Pierfilippo; Casali, Paolo; Dei Tos, Angelo P; Rossi, Sabrina; Rizzo, Sergio; Badalamenti, Giuseppe; Tomasino, Rosa Maria; Russo, Antonio; Butrynski, James E; Tonini, Giuseppe

    2012-04-01

    Soft tissue sarcomas are aggressive tumors representing alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7-41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down-regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis. Copyright © 2011 Wiley Periodicals, Inc.

  5. Stent therapy for malignant superior vena cava syndrome: Should be first line therapy or simple adjunct to radiotherapy

    International Nuclear Information System (INIS)

    Chatziioannou, A.; Alexopoulos, Th.; Mourikis, D.; Dardoufas, K.; Katsenis, K.; Lazarou, S.; Koutoulidis, V.; Ladopoulos, Ch.; Vlachos, L.

    2003-01-01

    The goal of this paper is to present our experience with superior vena cava (SVC) stenting, as first line procedure for immediate relief, in patients with malignancy, and its potential influence in the subsequent radiotherapy (XRT). Over a 1-year period, 18 patients with SVC syndrome due to severe stenosis secondary to mediastinal malignancy were referred for stent insertion. A SVC score was used to measure treatment effectiveness. Stent insertion had been successful in 18/18 patients (technical success 100%). All patients experienced symptomatic relief within few hours of the procedure. There were no major complications. In all patients we were able to start radiotherapy (XRT) the next day, after stenting according to our new institutional protocol. All patients were able to comply with the XRT program, perfectly well. Conclusions: SVC stenting provides immediate significant relief of the very annoying SVC syndrome symptoms, thus facilitating excellent compliance of all the patients to the subsequently XRT protocols. We strongly recommend SVC stenting as first line procedure, in patients with SVC syndrome due to malignancy prior to radiotherapy

  6. Nanoscaled hydrated antimony (V oxide as a new approach to first-line antileishmanial drugs

    Directory of Open Access Journals (Sweden)

    Franco AMR

    2016-12-01

    Full Text Available Antonia MR Franco,1 Iryna Grafova,2 Fabiane V Soares,1,3 Gennaro Gentile,4 Claudia DC Wyrepkowski,1,3 Marcos A Bolson,5 Ézio Sargentini Jr,5 Cosimo Carfagna,4 Markku Leskelä,2 Andriy Grafov2 1Laboratory of Leishmaniasis and Chagas Disease, National Institute of Amazonian Research (INPA, Manaus, Amazonas, Brazil; 2Department of Chemistry, University of Helsinki, Helsinki, Finland; 3Multi-Institutional Post-Graduate Program in Biotechnology, Federal University of Amazonas, Manaus, Amazonas, Brazil; 4Institute for Polymers, Composites, and Biomaterials, National Research Council, Pozzuoli, Naples Province, Italy; 5Laboratory of Environmental Chemistry, National Institute of Amazonian Research (INPA, Manaus, Amazonas, Brazil Background: Coordination compounds of pentavalent antimony have been, and remain, the first-line drugs in leishmaniasis treatment for >70 years. Molecular forms of Sb (V complexes are commercialized as sodium stibogluconate (Pentostam® and meglumine antimoniate (MA (Glucantime®. Ever-increasing drug resistance in the parasites limits the use of antimonials, due to the low drug concentrations being administered against high parasitic counts. Sb5+ toxicity provokes severe side effects during treatment. To enhance therapeutic potency and to increase Sb (V concentration within the target cells, we decided to try a new active substance form, a hydrosol of Sb2O5⋅nH2O nanoparticles (NPs, instead of molecular drugs. Methodology/principal findings: Sb2O5⋅nH2O NPs were synthesized by controlled SbCl5 hydrolysis in a great excess of water. Sb2O5⋅nH2O phase formation was confirmed by X-ray diffraction. The surface of Sb (V NPs was treated with ligands with a high affinity for target cell membrane receptors. The mean particle size determined by dynamic light scattering and transmission electron microscopy was ~35–45 nm. In vitro tests demonstrated a 2.5–3 times higher antiparasitic activity of Sb (V nanohybrid hydrosols

  7. First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

    Science.gov (United States)

    Peinemann, Frank; Grouven, Ulrich; Kröger, Nicolaus; Bartel, Carmen; Pittler, Max H.; Lange, Stefan

    2011-01-01

    Introduction Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. Methods A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. Results 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. Conclusions Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. PMID:21541024

  8. Multiple needle-pass percutaneous testicular sperm aspiration as first-line treatment in azoospermic men

    DEFF Research Database (Denmark)

    Jensen, C F S; Ohl, D A; Hiner, M R

    2016-01-01

    spermatozoa found for intracytoplasmic sperm injection in a subsequent therapeutic TESA. In nine NOA men in whom a TESA produced no spermatozoa, only one had spermatozoa found with mTESE. Overall complication rates of TESA and mTESE were 3% (7/267) and 21% (3/14), respectively. TESA provides reasonable SRR...... and is a safe procedure. Successful prognostic TESA indicates future success with therapeutic TESA. Men with a failed TESA have a limited chance of sperm retrieval using mTESE. Approaching azoospermic men with an initial prognostic TESA followed by either therapeutic TESA and/or mTESE is an efficient algorithm...

  9. Trial efficacy vs real world effectiveness in first line treatment of multiple myeloma

    NARCIS (Netherlands)

    Liwing, J.; Heeg, B.M.; Karstorp, S.; Postma, M.; Silvennoinen, R.; Putkonen, M.; Anttila, P.; Remes, K.; Abildgaard, N.; Waage, A.; Nahi, H.

    2015-01-01

    Background: Large randomized clinical trials (RCT) are the foundation of the registration of newly developed drugs. A potential problem with RCTs is that the inclusion/exclusion criteria will make the population different from the actual population treated in real life. Hence, it is important to

  10. PENGARUH PSYCHOLOGICAL EMPOWERMENT, EMPOWERING LEADERSHIP, SISTEM PENGUKURAN KINERJA PADA MOTIVASI INTRINSIK FIRST-LINE EMPLOYEES PERBANKAN

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Purnamawati

    2016-10-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui pengaruh Psychological Empowerment, Empowering Leadership, dan Sistem Pengukuran Kinerja Pada Motivasi Intrinsik First-Line Employees Perbankan. Penelitian ini adalah penelitian kuantitatif. Data yang digunakan adalah data primer berupa kuesioner yang menggunakan skala likert 1-5 dan terdiri atas 36 item pertanyaan. Responden pada penelitian ini adalah manajemen lini garis pertama pada sektor perbankan yaitu sejumlah 35 orang yang berasal dari 7 BPR yang ada di Kabupaten Buleleng. Metode analisis data menggunakan model regresi linear berganda dengan bantuan alat statistik SPSS. Hasil penelitian menunjukkan bahwa  Psychological Empowerment, Empowering Leadership, dan Sistem Pengukuran Kinerja berpengaruh positif dan signifikan pada Motivasi Intrinsik First-Line Employees Perbankan dengan menggunakan taraf signifikansi 5%.

  11. Review of the first line supervisory positions in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Mullin, D; Mackenzie, C W [Hickling Corp. (Canada)

    1995-10-01

    The authors review the nature of the tasks performed by first line maintenance supervisors in three nuclear power plants. They compare these tasks to core supervisory training curriculum, supervisory job descriptions, and both the process related to performance appraisals, and the criteria applied in carrying out these performance evaluations. Recommendations have been made concerning methods of increasing the relevancy of training and improving the performance appraisal process. ( author). 5 figs.

  12. Review of the first line supervisory positions in nuclear power plants

    International Nuclear Information System (INIS)

    Mullin, D.; Mackenzie, C.W.

    1995-10-01

    The authors review the nature of the tasks performed by first line maintenance supervisors in three nuclear power plants. They compare these tasks to core supervisory training curriculum, supervisory job descriptions, and both the process related to performance appraisals, and the criteria applied in carrying out these performance evaluations. Recommendations have been made concerning methods of increasing the relevancy of training and improving the performance appraisal process. ( author). 5 figs

  13. Power in health care organizations: contemplations from the first-line management perspective.

    Science.gov (United States)

    Isosaari, Ulla

    2011-01-01

    The aim of this paper is to examine health care organizations' power structures from the first-line management perspective. What liable power structures derive from the theoretical bases of bureaucratic, professional and result based organizations, and what power type do health care organizations represent, according to the empirical data? The paper seeks to perform an analysis using Mintzberg's power configurations of instrument, closed system, meritocracy and political arena. The empirical study was executed at the end of 2005 through a survey in ten Finnish hospital districts in both specialized and primary care. Respondents were all first-line managers in the area and a sample of staff members from internal disease, surgical and psychiatric units, as well as out-patient and primary care units. The number of respondents was 1,197 and the response percentage was 38. The data were analyzed statistically. As a result, it can be seen that a certain kind of organization structure supports the generation of a certain power type. A bureaucratic organization generates an instrument or closed system organization, a professional organization generates meritocracy and also political arena, and a result-based organization has a connection to political arena and meritocracy. First line managers regarded health care organizations as instruments when staff regarded them mainly as meritocracies having features of political arena. Managers felt their position to be limited by rules, whereas staff members regarded their position as having lots of space and influence potential. If the organizations seek innovative and active managers at the unit level, they should change the organizational structure and redistribute the work so that there could be more space for meaningful management. This research adds to the literature and gives helpful suggestions that will be of interest to those in the position of first-line management in health care.

  14. First-line managers' experiences of alternative modes of funding in elderly care in Sweden.

    Science.gov (United States)

    Antonsson, Helen; Korjonen, Susanne Eriksson; Rosengren, Kristina

    2012-09-01

    The aim of this study was to describe first-line managers' experiences of alternative modes of funding elderly care in two communities in western Sweden. A growing elderly population demands alternative modes of funding elderly care for better outcomes for patients and better efficiency as it is publicly funded through taxation. The study comprised a total of eight semi-structured interviews with first-line managers working within elderly care. The interviews were analysed using manifest qualitative content analysis. Respect for the individuals was a main concern in the study. One category, quality improvement, and four subcategories freedom of choice, organisational structure, quality awareness and market forces effects were identified to describe first-line managers' experiences of the operation of elderly care. Quality improvement was an important factor to deal with when elderly care was operated in different organisational perspectives, either private or public. The first-line manager is a key person for developing a learning organisation that encourages both staff, clients and their relatives to improve the organisation. Moreover, person-centred care strengthens the client's role in the organisation, which is in line with the government's goal for the quality improvement of elderly care. However, further research is needed on how quality improvement could be developed when different caregivers operate in the same market in order to improve care from the elderly perspective. This study highlights alternative modes of funding elderly care. The economical perspectives should not dominate without taking care of quality improvement when the operation of elderly care is planned and implemented. Strategies such as a learning organisational structure built on person-centred care could create quality improvement in elderly care. © 2012 Blackwell Publishing Ltd.

  15. Resilience and work-life balance in first-line nurse manager.

    Science.gov (United States)

    Kim, Miyoung; Windsor, Carol

    2015-03-01

    The aim of this study was to explore how first-line nurse managers constructed the meaning of resilience and its relationship to work-life balance for nurses in Korea. Participants were 20 first-line nurse managers working in six university hospitals. Data were collected through in-depth interviews from December 2011 to August 2012, and analyzed using Strauss and Corbin's grounded theory method. Analysis revealed that participants perceived work-life balance and resilience to be shaped by dynamic, reflective processes. The features consisting resilience included "positive thinking", "flexibility", "assuming responsibility", and "separating work and life". This perception of resilience has the potential to facilitate a shift in focus from negative to positive experiences, from rigidity to flexibility, from task-centered to person-centered thinking, and from the organization to life. Recognizing the importance of work-life balance in producing and sustaining resilience in first-line nurse managers could increase retention in the Korean nursing workforce. Copyright © 2015. Published by Elsevier B.V.

  16. Managerial competence of first-line nurse managers: A concept analysis.

    Science.gov (United States)

    Gunawan, Joko; Aungsuroch, Yupin

    2017-02-01

    A variety of terms are used interchangeably to define managerial competence of first-line nurse managers. This has resulted in a degree of ambiguity in the way managerial competence is described. The aim of this concept analysis is to clarify what is meant by managerial competence of first-line nurse managers internationally, what attributes signify it, and what its antecedents and consequences are. The Walker and Avant concept analysis approach was applied. The attributes of managerial competence include developing self, planning, organizing, leading, managing legal and ethical issues, and delivering health care. Antecedents to managerial competence include internal and external factors. Consequences include nurse performances, nurse and patient outcomes, intention to stay of nurses, and nurse and patient satisfaction. This analysis helps first-line nurse managers to understand the concept and determine where the responsibility lies in establishing a definition of managerial competence. It is recommended that middle and top managers should be aware of the internal and external factors as antecedents of the concept. Further research is needed to illuminate the attributes of managerial competence in relation to antecedents and the potential effect upon the consequences, and the need to establish managerial competence evaluation. © 2017 John Wiley & Sons Australia, Ltd.

  17. The holistic management of consequences of cancer treatment by a gastrointestinal and nutrition team: a financially viable approach to an enormous problem?

    Science.gov (United States)

    Muls, Ann C; Lalji, Amyn; Marshall, Christopher; Butler, Lewis; Shaw, Clare; Vyoral, Susan; Mohammed, Kabir; Andreyev, H Jervoise N

    2016-06-01

    There is no national NHS tariff to fund services for patients experiencing long-term bowel and nutritional problems after cancer treatment. In this paper, we report the clinical characteristics and outcomes of patients referred to our service and the estimated cost of a completed episode of care. Patient characteristics, symptom severity, investigations, diagnoses, number of clinic visits and referrals elsewhere were recorded in a prospective cohort study. During 2013-14, 325 patients completed assessment and treatment. The majority of original cancer diagnoses were urological (43%) and gynaecological (21%). A median of six investigations were requested. 62% were found to have three or more new diagnoses including small intestinal bacterial overgrowth (46%), vitamin D deficiency (38%), bile acid malabsorption (28%), gastritis (22%), radiation-induced bleeding (20%), vitamin B12 deficiency (17%), pelvic floor weakness (17%), colorectal polyps (13%) and pancreatic insufficiency (5%). A median of three visits were required and all commonly reported gastrointestinal symptoms improved by discharge. The mean episode of care per patient was costed at £1,563. Effective amelioration of chronic gastrointestinal toxicity after cancer treatment costs substantially less than treating the cancer in the first place and requires an NHS tariff. © 2016 Royal College of Physicians.

  18. Do Veterans With Posttraumatic Stress Disorder Receive First-Line Pharmacotherapy? Results From the Longitudinal Veterans Health Survey

    Science.gov (United States)

    Greenbaum, Mark A.; Rosen, Craig S.

    2012-01-01

    Objective: Guidelines addressing the treatment of veterans with posttraumatic stress disorder (PTSD) strongly recommend a therapeutic trial of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This study examined veteran characteristics associated with receiving such first-line pharmacotherapy, as well as how being a veteran of the recent conflicts in Afghanistan and Iraq impact receipt of pharmacotherapy for PTSD. Method: This was a national study of 482 Veterans Affairs (VA) outpatients between the ages of 18 and 69 years who had been newly diagnosed with PTSD (DSM-IV criteria: 309.81) during a VA outpatient visit between May 31, 2006, and December 7, 2007. Participants completed a mailed survey between August 11, 2006, and April 6, 2008. Veterans from the Afghanistan and Iraq conflicts and female veterans were intentionally oversampled. Logistic regression models were developed to predict 2 dependent variables: odds of initiating an SSRI/SNRI and, among veterans who initiated an SSRI/SNRI, odds of receiving an adequate therapeutic trial. Each dependent variable was regressed on a variety of sociodemographic and survey characteristics. Results: Of the 377 veterans prescribed a psychotropic medication, 73% (n = 276) received an SSRI/SNRI, of whom 61% (n = 168) received a therapeutic trial. Afghanistan and Iraq veterans were less likely to receive a therapeutic trial (odds ratio [OR] = 0.45; 95% CI, 0.27–0.75; P < .01), with presence of a comorbid depression diagnosis in the year after the index episode moderating this relationship, which further decreased the odds of completing a therapeutic trial (OR = 0.29; 95% CI, 0.09–0.95; P < .05). Conclusions: Reduced levels of receipt of first-line pharmacotherapy among recent veteran returnees parallel previous findings of less mental health treatment utilization in this population and warrant investigation. PMID:22943028

  19. Vinorelbine as first-line or second-line therapy for advanced breast cancer

    DEFF Research Database (Denmark)

    Langkjer, Sven T; Ejlertsen, Bent; Mouridsen, Henning

    2008-01-01

    INTRODUCTION: This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. PATIENTS AND METHODS: Patients had histologically...... proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks' schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. RESULTS: Fifty...

  20. Mobilizing First-Line Managers as Organizational Strategy Makers: The Case of Environmentally Sustainable Operations

    OpenAIRE

    Gjøsæter, Åge

    2013-01-01

    The purpose of the paper is to investigate how first-line managers are mobilized as organizational strategy makers. The research case is a campaign launched by a Norwegian shipping company servicing the petroleum industry. The strategic idea on which the campaign was based was to operate the company`s fleet of offshore service vessels in an environmentally sustainable way, to be realized by carrying out fuel-saving operations on board the vessels. A strategic idea is supposed to set out a vie...

  1. Clinical Relevance of Alternative Endpoints in Colorectal Cancer First-Line Therapy With Bevacizumab: A Retrospective Study.

    Science.gov (United States)

    Turpin, Anthony; Paget-Bailly, Sophie; Ploquin, Anne; Hollebecque, Antoine; Peugniez, Charlotte; El-Hajbi, Farid; Bonnetain, Franck; Hebbar, Mohamed

    2018-03-01

    We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab. We assessed OS, progression-free survival (PFS), duration of disease control (DDC), the sum of the periods in which the disease did not progress, and the time to failure of strategy (TFS), which was defined as the entire period before the introduction of a second-line treatment. Linear correlation and regression models were used, and Prentice criteria were investigated. With a median follow-up of 57.6 months for 216 patients, the median OS was 24.5 months (95% confidence interval [CI], 21.3-29.7). The median PFS, DDC, and TFS were 8.9 (95% CI, 8.4-9.7), 11.0 (95% CI, 9.8-12.4), and 11.1 (95% CI, 10.0-13.0) months, respectively. The correlations between OS and DDC (Pearson coefficient, 0.79 [95% CI, 0.73-0.83], determination coefficient, 0.62) and OS and TFS (Pearson coefficient, 0.79 [95% CI, 0.73-0.84], determination coefficient, 0.63) were satisfactory. Linear regression analysis showed a significant association between OS and DDC, and between OS and TFS. Prentice criteria were verified for TFS as well as DDC. DDC and TFS correlated with OS and are relevant as intermediate criteria in the setting of patients with mCRC treated with a first-line bevacizumab-based regimen. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Responsibilities and commitment of top management and first line management in organizational-level interventions - what difference does it make?

    DEFF Research Database (Denmark)

    Gish, Liv; Ipsen, Christine; Poulsen, Signe

    Researchers advocate that interventions should apply a participatory approach i.e. employee participation. It is also widely recognized that top management’s support is an important part of a successful intervention implementation. Lately there has been a request for multi-level intervention...... momentum and increase chances of successful implementation. Four SMEs participated in the study. The typical intervention construct was that top management initiated the intervention and first line managers had to manage the intervention on a daily basis together with two selected employees who acted as in...... between top management and first line management. The top manager’s most important responsibilities were to ensure that the first line manager understood the purpose of the intervention, and to support the first line manager’s dispositions through the intervention. The first line manager’s most important...

  3. Rates and factors associated with major modifications to first-line combination antiretroviral therapy: results from the Asia-Pacific region.

    Directory of Open Access Journals (Sweden)

    Stephen Wright

    Full Text Available In the Asia-Pacific region many countries have adopted the WHO's public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART in resource-rich and resource-limited countries in the region.We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD and the TREAT Asia HIV Observational Database (TAHOD. We dichotomised each country's per capita income into high/upper-middle (T-H and lower-middle/low (T-L. Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV or a substitution of two or more ARV agents from within the same ARV class.A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI of treatment modification was 0.48 (0.44-0.52, 0.33 (0.30-0.36 and 0.21 (0.18-0.23 for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL, quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL, monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring.Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increased rate of RNA-VL monitoring was

  4. [Clinical observation of icotinib hydrochloride in first-line therapy for pulmonary adenocarcinoma].

    Science.gov (United States)

    Yang, Xinjie; Zhang, Hui; Qin, Na; Li, Xi; Nong, Jingying; Lv, Jialin; Wu, Yuhua; Zhang, Quan; Zhang, Shucai

    2013-07-01

    It has been proven that icotinib hydrochloride, as a molecule targeted drug, can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC) for second-line or third-line. This research was aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the first-line therapy for pulmonary adenocarcinoma. Among the 56 patients, the tumor objective response rate (ORR) and disease control rate (DCR) was 46.4% (26/56) and 78.6% (46/56), respectively. Among the 20 patients with EGFR analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18), DCR was 94.4% (17/18) respectively. The ORR with no history of smoke. EGFR positive mutation and appearance of rash were significantly higher than those with smoker, wild type EGFR, no information about EGFR and no appearance of rash (Picotinib hydrochloride is effective and tolerable in first-line therapy for pulmonary adenocarcinoma, especially with EGFR mutation.

  5. First-line managers' descriptions and reflections regarding their staff's access to empowering structures.

    Science.gov (United States)

    Skytt, Bernice; Hagerman, Heidi; Strömberg, Annika; Engström, Maria

    2015-11-01

    To elucidate first-line managers' descriptions and reflections regarding their staff's access to empowering structures using Kanter's theory of structural empowerment. Good structural conditions within workplaces are essential to employees' wellbeing, and their ability to access empowerment structures is largely dependent on the management. Twenty-eight first-line managers in elderly care were interviewed. Deductive qualitative content analysis was used to analyse data. Managers perceived that staff had varying degrees of access to the empowering structures described in Kanter's theory - and that they possessed formal power in their roles as contact persons and representatives. The descriptions mostly started from the managers' own actions, although some started from the needs of staff members. All managers described their staff's access to the empowering structures in Kanter's theory as important, yet it seemed as though this was not always reflected on and discussed as a strategic issue. Managers could make use of performance and appraisal dialogues to keep up to date on staff's access to empowering structures. Recurrent discussions in the management group based on such current information could promote staff's access to power through empowering structures and make job definitions a strategic issue in the organisation. © 2014 John Wiley & Sons Ltd.

  6. Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups

    Directory of Open Access Journals (Sweden)

    Macedo Ligia

    2012-03-01

    Full Text Available Abstract Background Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens. Methods A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen. Results Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS and progression-free survival (PFS (HR = 0.84; CI: 0.77-0.91; P Conclusions Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.

  7. Economic impact of simplified de Gramont regimen in first-line therapy in metastatic colorectal cancer.

    Science.gov (United States)

    Limat, Samuel; Bracco-Nolin, Claire-Hélène; Legat-Fagnoni, Christine; Chaigneau, Loic; Stein, Ulrich; Huchet, Bernard; Pivot, Xavier; Woronoff-Lemsi, Marie-Christine

    2006-06-01

    The cost of chemotherapy has dramatically increased in advanced colorectal cancer patients, and the schedule of fluorouracil administration appears to be a determining factor. This retrospective study compared direct medical costs related to two different de Gramont schedules (standard vs. simplified) given in first-line chemotherapy with oxaliplatin or irinotecan. This cost-minimization analysis was performed from the French Health System perspective. Consecutive unselected patients treated in first-line therapy by LV5FU2 de Gramont with oxaliplatin (Folfox regimen) or with irinotecan (Folfiri regimen) were enrolled. Hospital and outpatient resources related to chemotherapy and adverse events were collected from 1999 to 2004 in 87 patients. Overall cost was reduced in the simplified regimen. The major factor which explained cost saving was the lower need for admissions for chemotherapy. Amount of cost saving depended on the method for assessing hospital stay. In patients treated by the Folfox regimen the per diem and DRG methods found cost savings of Euro 1,997 and Euro 5,982 according to studied schedules; in patients treated by Folfiri regimen cost savings of Euro 4,773 and Euro 7,274 were observed, respectively. In addition, travel costs were also reduced by simplified regimens. The robustness of our results was showed by one-way sensitivity analyses. These findings demonstrate that the simplified de Gramont schedule reduces costs of current first-line chemotherapy in advanced colorectal cancer. Interestingly, our study showed several differences in costs between two costing approaches of hospital stay: average per diem and DRG costs. These results suggested that standard regimen may be considered a profitable strategy from the hospital perspective. The opposition between health system perspective and hospital perspective is worth examining and may affect daily practices. In conclusion, our study shows that the simplified de Gramont schedule in combination with

  8. Rapid first-line discrimination of methicillin resistant Staphylococcus aureus strains using MALDI-TOF MS

    DEFF Research Database (Denmark)

    Østergaard, Claus; Grønvall Kjær Hansen, Sanne; Møller, Jens K

    2015-01-01

    /z-values (peaks) and used a concept of arranging these peaks into pairs or small clusters within a small mass range, allowing for quality control of the spectra obtained. Using this concept we could reproducibly characterise and arrange the isolates into 26 MALDI-TOF groups, which strongly correlated with spa...... used for this purpose. These methods are all relatively time-consuming and not performed routinely in all laboratories. The aim of this study is to examine whether MALDI-TOF MS can be used as a fast, simple and easily implemented method for first-line discrimination of MRSA isolates. Mass spectra from...... 600 clinical MRSA isolates were included in the study, representing 89 spa types, associated with 16 different known clonal complexes. All spectra were obtained directly from colony material obtained from overnight cultures without prior protein extraction. We identified 43 useful discriminatory m...

  9. First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas.

    Science.gov (United States)

    Frenay, M P; Fontaine, D; Vandenbos, F; Lebrun, C

    2005-09-01

    At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low-grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in order to reduce or delay tumor progression or symptoms, despite possible long-term neurologic complications. We report 10 patients, with histologically proven pure low-grade fibrillary astrocytomas, to which we administered a first-line nitrosourea-based CT. All patients were symptomatic with pharmaco-resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure-free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow-up of 6.5 years (3.5-12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non-resectable fibrillary low-grade astrocytomas can be treated with up-front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT.

  10. The Effects of First-Line Anti-Tuberculosis Drugs on the Actions of Vitamin D in Human Macrophages.

    Science.gov (United States)

    Chesdachai, Supavit; Zughaier, Susu M; Hao, Li; Kempker, Russell R; Blumberg, Henry M; Ziegler, Thomas R; Tangpricha, Vin

    2016-12-01

    Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1N1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH) 2 D 3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease of hCAP18 mRNA at the dosage of 10 ug/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D 3 (1.2 million IU over 8 weeks, n=13) versus placebo (n=18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18.These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages.

  11. Everolimus plus exemestane as first-line therapy in HR⁺, HER2⁻ advanced breast cancer in BOLERO-2.

    Science.gov (United States)

    Beck, J Thaddeus; Hortobagyi, Gabriel N; Campone, Mario; Lebrun, Fabienne; Deleu, Ines; Rugo, Hope S; Pistilli, Barbara; Masuda, Norikazu; Hart, Lowell; Melichar, Bohuslav; Dakhil, Shaker; Geberth, Matthias; Nunzi, Martina; Heng, Daniel Y C; Brechenmacher, Thomas; El-Hashimy, Mona; Douma, Shyanne; Ringeisen, Francois; Piccart, Martine

    2014-02-01

    The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR(+), HER2(-) advanced breast cancer in postmenopausal patients.

  12. Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

    Science.gov (United States)

    Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

    2016-09-01

    To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

  13. Regimen durability in HIV-infected children and adolescents initiating first-line ART in a large public sector HIV cohort in South Africa.

    Science.gov (United States)

    Bonawitz, Rachael; Brennan, Alana T; Long, Lawrence; Heeren, Timothy; Maskew, Mhairi; Sanne, Ian; Fox, Matthew P

    2018-04-15

    In April 2010 tenofovir and abacavir replaced stavudine in public-sector first-line antiretroviral therapy (ART) for children under 20 years old in South Africa. The association of both abacavir and tenofovir with fewer side-effects and toxicities compared to stavudine could translate to increased durability of tenofovir or abacavir-based regimens. We evaluated changes over time in regimen durability for pediatric patients 3 to 19 years of age at 8 public sector clinics in Johannesburg, South Africa. Cohort analysis of treatment naïve, non-pregnant pediatric patients from 3 to 19 years old initiated on ART between April 2004-December 2013. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir and/or abacavir was substituted for stavudine after April 2010 in first-line ART. We evaluated the frequency and type of single-drug substitutions, treatment interruptions, and switches to second-line therapy. Fine and Gray competing risk regression models were used to evaluate the association of antiretroviral drug type with single-drug substitutions, treatment interruptions, and second-line switches in the first 24-months on treatment. 398 (15.3%) single-drug substitutions, 187 (7.2%) treatment interruptions and 86 (3.3%) switches to second-line therapy occurred among 2602 pediatric patients over 24-months on ART. Overall, the rate of single-drug substitutions started to increase in 2009, peaked in 2011 at 25%, then declined to 10% in 2013, well after the integration of tenofovir into pediatric regimens; no patients over the age of 3 were initiated on abacavir for first-line therapy. Competing risk regression models showed patients on zidovudine or stavudine had upwards of a 5-fold increase in single-drug substitution vs. patients initiated on tenofovir in the first 24-months on ART. Older adolescents also had a 2-3-fold increase in treatment interruptions and switches to second

  14. Current status of first-line therapy for elderly patients with proatate cancer in Kyushu and Okinawa areas. A questionnaire study

    International Nuclear Information System (INIS)

    Nishiyama, Kenryu; Nakagawa, Masayuki; Koga, Hirofumi

    2005-01-01

    A survey based on a questionnaire to urologists in Kyushu and Okinawa areas was carried out to assess the current status of first-line therapy for elderly patients with prostate cancer. Ninety-three urologists from 93 institutes answered the questionnaire. Endocrine therapy is widely performed as first-line therapy for elderly patients with prostate cancer. They mostly receive immediate-continuous therapy regardless of their clinical factors. Only 8 (9%) and 7 (8%) institutes have the options of deferred and intermittent therapy, respectively. LH-RH analogue and non-steroidal anti-androgens are commonly used. Chemoendocrine therapy is performed in 33 (35%) institutes for selected patients. Estramustine and 5-fluorouracil (5-FU) derivatives are commonly used as chemotherapeutic agents. Sixty (65%) institutes do not have this modality as a treatment option. Risks arising from the treatment and quality of life (QOL) disturbance are the main reasons for this. Radiation therapy and radical prostatectomy are performed in 53 (57%) and 47 (51%) institutes, respectively, for selected patients with loco-regional disease. However, 22 (24%) institutes do not have these definitive therapies as treatment options. QOL and risks arising from the treatments are the main factors for selecting definitive or non-definitive therapy. In elderly patients with prostate cancer, cancer control is not always the goal of treatment. QOL within a relatively shorter life expectancy is an important factor for decision making in the management of these patients. (authors)

  15. PROGNOSTIC FACTORS FOR SURVIVAL IN PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED WITH FIRST - LINE CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2017-05-01

    Full Text Available Objective: The aim of this study was to investigate the prognostic significance for survival of certain clinical and pathological factors in patients with advanced or metastatic colorectal carcinoma (CRC treated with first- line chemotherapy. Methods: From 2002 to 2011 seventy- four consecutive patients with advanced or metastatic CRC, treated in UMHAT- Dr. G. Stranski, Department of Medical Oncology entered the study. Some patient’s characteristics, hematological and pathological parameters, were evaluated for their role as predictors of overall survival. The therapeutic regimens included FOLFOX or FOlFIRI. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment characteristics as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: In multivariate analysis a significant correlation was exhibited between survival, poor performance status and multiple sites of metastasis. Variables significantly associated with overall survival in univariate analysis were performance status>1, thrombocytosis, anemia and number of metastatic sites >1. Conclusion: These results indicated that poor performance status, anemia, thrombocytosis as well as multiple site of metastasis could be useful prognostic factors in patients with metastatic CRC.

  16. Role stress among first-line nurse managers and registered nurses - a comparative study.

    Science.gov (United States)

    Johansson, Gunilla; Sandahl, Christer; Hasson, Dan

    2013-04-01

    Studies show that first-line nurse managers (F-LNMs) experience high psychological job demands and inadequate managerial guidance. The purpose of this study was to investigate whether F-LNMs have higher stress levels and show more signs of stress-related ill health than registered nurses (RNs). The aim of this study was to examine possible differences in self-rated health between F-LNMs and RNs on various psychosocial factors (e.g. job demand, job control and managerial support). Data were collected at a university hospital in Sweden. Sixty-four F-LNMs and 908 RNs filled in a web-based questionnaire. Both F-LNMs and RNs reported having good health. Approximately 10-15% of the F-LNMs and RNs showed signs of being at risk for stress-related ill health. Statistically significant differences (Mann-Whitney U-test) were found in the distribution between the F-LNMs and the RNs on three indices of job control, job demand and managerial support. Our findings suggest that F-LNMs were able to cope with high-demand job situations because of relatively high control over work. The implication for nursing management shows the needs for a work environment for both F-LNMs and RNs that includes high job control and good managerial support. © 2011 Blackwell Publishing Ltd.

  17. Experience with ibrutinib for first-line use in patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Itchaki, Gilad; Brown, Jennifer R

    2018-01-01

    Ibrutinib is the first in-class, orally administered, Bruton's tyrosine kinase (BTK) inhibitor that abrogates the critical signaling downstream of the B-cell receptor (BCR). This signaling is required for B-cell survival, proliferation and interaction with the microenvironment. Ibrutinib proved active in preclinical models of lymphoproliferative diseases and achieved impressive response rates in heavily pretreated relapsed and refractory (R/R) patients with chronic lymphocytic leukemia (CLL). Ibrutinib prolonged survival compared to standard therapy and mitigated the effect of most poor prognostic factors in CLL, thus becoming the main therapeutic option in high-risk populations. Moreover, compared with standard chemoimmunotherapy (CIT) for adults, ibrutinib causes fewer cytopenias and infections, while having its own unique toxicity profile. Its efficacy in relapsed patients as well as its tolerability have led to its increased use in previously untreated patients, especially in those with poor prognostic markers and/or the elderly. This review elaborates on ibrutinib's unique toxicity profile and the mechanisms of acquired resistance leading to progression on ibrutinib, since both are critical for understanding the obstacles to its first-line use. We will further evaluate the data from ongoing clinical trials in this setting and explore future options for combination therapy.

  18. Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy.

    Science.gov (United States)

    Etiebet, Mary-Ann A; Shepherd, James; Nowak, Rebecca G; Charurat, Man; Chang, Harry; Ajayi, Samuel; Elegba, Olufunmilayo; Ndembi, Nicaise; Abimiku, Alashle; Carr, Jean K; Eyzaguirre, Lindsay M; Blattner, William A

    2013-02-20

    In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4). At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.

  19. Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis.

    Science.gov (United States)

    Birolo, Carolina; Zannin, Maria Elisabetta; Arsenyeva, Svetlana; Cimaz, Rolando; Miserocchi, Elisabetta; Dubko, Margarita; Deslandre, Chantal Job; Falcini, Fernanda; Alessio, Maria; La Torre, Francesco; Denisova, Ekaterina; Martini, Giorgia; Nikishina, Irina; Zulian, Francesco

    2016-11-01

    Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)-associated uveitis refractory to anti-tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis. In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded. Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile. ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

  20. Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study).

    Science.gov (United States)

    Zaanan, Aziz; Samalin, Emmanuelle; Aparicio, Thomas; Bouche, Olivier; Laurent-Puig, Pierre; Manfredi, Sylvain; Michel, Pierre; Monterymard, Carole; Moreau, Marie; Rougier, Philippe; Tougeron, David; Taieb, Julien; Louvet, Christophe

    2018-04-01

    In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m 2  q3w) to cisplatin (75 mg/m 2  q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated. GASTFOX study is a randomized phase III trial comparing FOLFOX alone or with docetaxel at 50 mg/m 2 (TFOX regimen) in first-line treatment for advanced gastric cancer. In both arms, cycle is repeated every 2 weeks until disease progression or unacceptable toxicity. Main eligibility criteria: histologically proven locally advanced or metastatic gastric or esogastric junction adenocarcinoma, HER negative status, measurable disease, ECOG performance status 0 or 1, and adequate renal, hepatic and bone marrow functions. The primary endpoint is radiological/clinical progression-free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (HR = 0.73) Based on a two-sided α risk of 5% and a power of 90%, 454 events are required to show this difference. Secondary endpoints included overall survival, overall response rate, safety, quality of life and the therapeutic index. This study is planned to include 506 patients to demonstrate the superiority of TFOX over FOLFOX in first-line advanced gastric cancer treatment (NCT03006432). Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  1. Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

    Science.gov (United States)

    Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

    2011-06-01

    First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

  2. Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy

    International Nuclear Information System (INIS)

    Farina, Davide; Morassi, Mauro; Maroldi, Roberto; Roca, Elisa; Tassi, Gianfranco; Cavalleri, Giuseppe

    2013-01-01

    To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. (orig.)

  3. Melanocytes and melanin represent a first line of innate immunity against Candida albicans.

    Science.gov (United States)

    Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna

    2014-07-01

    Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Viable Syntax: Rethinking Minimalist Architecture

    Directory of Open Access Journals (Sweden)

    Ken Safir

    2010-03-01

    Full Text Available Hauser et al. (2002 suggest that the human language faculty emerged as a genetic innovation in the form of what is called here a ‘keystone factor’—a single, simple, formal mental capability that, interacting with the pre-existing faculties of hominid ancestors, caused a cascade of effects resulting in the language faculty in modern humans. They take Merge to be the keystone factor, but instead it is posited here that Merge is the pre-existing mechanism of thought made viable by a principle that permits relations interpretable at the interfaces to be mapped onto c-command. The simplified minimalist architecture proposed here respects the keystone factor as closely as possible, but is justified on the basis of linguistic analyses it makes available, including a relativized intervention theory applicable across Case, scope, agreement, selection and linearization, a derivation of the A/A’-distinction from Case theory, and predictions such as why in situ wh-interpretation is island-insensitive, but susceptible to intervention effects.

  5. [The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

    Science.gov (United States)

    Chen, H; Wang, H P; Zhang, L; Si, X Y

    2017-01-01

    Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

  6. An empirical evaluation of competency requirements for first-line managers to deal with resistance to change.

    OpenAIRE

    2007-01-01

    The point of departure of this study is that first-line managers play a pivotal role in the facilitation of change initiatives in organisations world-wide. Resistance to change is one of the primary reasons why change interventions fail or why success is not achieved in the change process. More specific, the inability of first-line managers to deal with resistance to change has been cited as a primary cause for change projects to fail. There is no evidence that any research has been conducted...

  7. High discordance in blood and genital tract HIV-1 drug resistance in Indian women failing first-line therapy.

    Science.gov (United States)

    Saravanan, Shanmugam; Gomathi, Selvamurthi; Delong, Allison; Kausalya, Bagavathi; Sivamalar, Sathasivam; Poongulali, Selvamuthu; Brooks, Katherine; Kumarasamy, Nagalingeswaran; Balakrishnan, Pachamuthu; Solomon, Sunil S; Cu-Uvin, Susan; Kantor, Rami

    2018-05-24

    Examine HIV-1 plasma viral load (PVL) and genital tract (GT) viral load (GVL) and drug resistance in India. At the YRG Centre for AIDS Research and Education, Chennai, we tested: PVL in women on first-line ART for ≥6 months; GVL when PVL >2000 copies/mL; and plasma, genital and proviral reverse transcriptase drug resistance when GVL >2000 copies/mL. Wilcoxon rank-sum and Fisher's exact tests were used to identify failure and resistance associations. Pearson correlations were calculated to evaluate PVL-GVL associations. Inter-compartmental resistance discordance was evaluated using generalized estimating equations. Of 200 women, 37% had detectable (>400 copies/mL) PVL and 31% had PVL >1000 copies/mL. Of women with detectable PVL, 74% had PVL >2000 copies/mL, of which 74% had detectable GVL. Higher PVL was associated with higher GVL. Paired plasma and genital sequences were available for 21 women; mean age of 34 years, median ART duration of 33 months, median CD4 count of 217 cells/mm3, median PVL of 5.4 log10 copies/mL and median GVL of 4.6 log10 copies/mL. Drug resistance was detected in 81%-91% of samples and 67%-76% of samples had dual-class resistance. Complete three-compartment concordance was seen in only 10% of women. GT-proviral discordance was significantly larger than plasma-proviral discordance. GT or proviral mutations discordant from plasma led to clinically relevant resistance in 24% and 30%, respectively. We identified high resistance and high inter-compartmental resistance discordance in Indian women, which might lead to unrecognized resistance transmission and re-emergence compromising treatment outcomes, particularly relevant to countries like India, where sexual HIV transmission is predominant.

  8. Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

    NARCIS (Netherlands)

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J. A.; Douillard, Jean-Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

    2015-01-01

    Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual

  9. Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART

    NARCIS (Netherlands)

    Lambert-Niclot, S.; George, E. C.; Pozniak, A.; White, E.; Schwimmer, C.; Jessen, H.; Johnson, M.; Dunn, D.; Perno, C. F.; Clotet, B.; Plettenberg, A.; Blaxhult, A.; Palmisano, L.; Wittkop, L.; Calvez, V.; Marcelin, A. G.; Raffi, F.; Dedes, Nikos; Chêne, Geneviève; Richert, Laura; Allavena, Clotilde; Raffi, François; Autran, Brigitte; Antinori, Andrea; Bucciardini, Raff Aella; Vella, Stefano; Horban, Andrzej; Arribas, Jose; Babiker, Abdel G.; Boffito, Marta; Pillay, Deenan; Pozniak, Anton; Franquet, Xavier; Schwarze, Siegfried; Grarup, Jesper; Fischer, Aurélie; Wallet, Cédrick; Diallo, Alpha; Molina, Jean-Michel; Saillard, Juliette; Moecklinghoff, Christiane; Stellbrink, Hans-Jürgen; van Leeuwen, Remko; Gatell, Jose; Sandstrom, Eric; Flepp, Markus; Ewings, Fiona; George, Elizabeth C.; Hudson, Fleur; Pearce, Gillian; Quercia, Romina; Rogatto, Felipe; Leavitt, Randi; Nguyen, Bach-Yen; Goebel, Frank; Marcotullio, Simone; Kaur, Navrup; Sasieni, Peter; Spencer-Drake, Christina; Peto, Tim; Miller, Veronica; Arnault, Fabien; Boucherie, Céline; Jean, Delphine; Paniego, Virginie; Paraina, Felasoa; Rouch, Elodie; Schwimmer, Christine; Soussi, Malika; Taieb, Audrey; Termote, Monique; Touzeau, Guillaume; Cursley, Adam; Dodds, Wendy; Hoppe, Anne; Kummeling, Ischa; Pacciarini, Filippo; Paton, Nick; Russell, Charlotte; Taylor, Kay; Ward, Denise; Aagaard, Bitten; Eid, Marius; Gey, Daniela; Jensen, Birgitte Gram; Jakobsen, Marie-Louise; Jansson, Per O.; Jensen, Karoline; Joensen, Zillah Maria; Larsen, Ellen Moseholm; Pahl, Christiane; Pearson, Mary; Nielsen, Birgit Riis; Reilev, Søren Stentoft; Christ, Ilse; Lathouwers, Desiree; Manting, Corry; Mendy, Bienvenu Yves; Metro, Annie; Couffin-Cadiergues, Sandrine; Knellwolf, Anne-Laure; Palmisiano, Lucia; Aznar, Esther; Barea, Cristina; Cotarelo, Manuel; Esteban, Herminia; Girbau, Iciar; Moyano, Beatriz; Ramirez, Miriam; Saiz, Carmen; Sanchez, Isabel; Yllescas, Maria; Binelli, Andrea; Colasanti, Valentina; Massella, Maurizio; Anagnostou, Olga; Gioukari, Vicky; Touloumi, Giota; Schmied, Brigitte; Rieger, Armin; Vetter, Norbert; de Wit, Stephane; Florence, Eric; Vandekerckhove, Linos; Gerstoft, Jan; Mathiesen, Lars; Katlama, Christine; Cabie, Andre; Cheret, Antoine; Dupon, Michel; Ghosn, Jade; Girard, Pierre-Marie; Goujard, Cécile; Lévy, Yves; Morlat, Philippe; Neau, Didier; Obadia, Martine; Perre, Philippe; Piroth, Lionel; Reynes, Jacques; Tattevin, Pierre; Ragnaud, Jean Marie; Weiss, Laurence; Yazdan, Yazdanpanah; Yeni, Patrick; Zucman, David; Behrens, Georg; Esser, Stefan; Fätkenheuer, Gerd; Hoffmann, Christian; Jessen, Heiko; Rockstroh, Jürgen; Schmidt, Reinhold; Stephan, Christoph; Unger, Stefan; Hatzakis, Angelos; Daikos, George L.; Papadopoulos, Antonios; Skoutelis, Athamasios; Banhegyi, Denes; Mallon, Paddy; Mulcahy, Fiona; Andreoni, Massimo; Bonora, Stefano; Castelli, Francesco; Monforte, Antonella D.'Arminio; Di Perri, Giovanni; Galli, Massimo; Lazzarin, Adriano; Mazzotta, Francesco; Carlo, Torti; Vullo, Vincenzo; Prins, Jan; Richter, Clemens; Verhagen, Dominique; van Eeden, Arne; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Sarmento-Castro, Rui; Garcia, Juan Gonzalez; Aldeguer, José López; Clotet, Bonaventura; Domingo, Pere; Gatell, Jose M.; Knobel, Hernando; Marquez, Manuel; Miralles, Martin Pilar; Portilla, Joaquin; Soriano, Vicente; Tellez, Maria-Jesus; Thalme, Anders; Blaxhult, Anders; Gisslen, Magnus; Winston, Alan; Fox, Julie; Gompels, Mark; Herieka, Elbushra; Johnson, Margaret; Leen, Clifford; Teague, Alastair; Williams, Ian; Boyd, Mark Alastair; Møller, Nina Friis; Larsen, Ellen Frøsig Moseholm; Le Moing, Vincent; Wit, Ferdinand W. N. M.; Kowalska, Justyna; Berenguer, Juan; Moreno, Santiago; Müller, Nicolas J.; Török, Estée; Post, Frank; Angus, Brian; Calvez, Vincent; Boucher, Charles; Collins, Simon; Dunn, David; Lambert, Sidonie; Marcelin, Anne-Geneviève; Perno, Carlo Federico; White, Ellen; Ammassari, Adriana; Stoehr, Wolgang; Schmidt, Reinhold Ernst; Odermarsky, Michal; Smith, Colette; Thiébaut, Rodolphe; de La Serna, Jose Ignacio Bernardino; Castagna, Antonella; Furrer, Hans-Jackob; Mocroft, Amanda; Reiss, Peter; Bucciardini, Raffaella; Fragola, Vincenzo; Lauriola, Marco; Murri, Rita; Nieuwkerk, Pythia; Spire, Bruno; Volny-Anne, Alain; West, Brian; Amieva, Hélène; Llibre Codina, Josep Maria; Braggion, Marco; Focà, Emanuele

    2016-01-01

    To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and

  10. A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity

    NARCIS (Netherlands)

    Tol, J.; Koopman, M.; Rodenburg, C. J.; Cats, A.; Creemers, G. J.; Schrama, J. G.; Erdkamp, F. L. G.; Vos, A. H.; Mol, L.; Antonini, N. F.; Punt, C. J. A.

    2008-01-01

    Targeting the vascular endothelial growth factor or the epidermal growth factor receptor (EGFR) has shown efficacy in advanced colorectal cancer (ACC), but no data are available on the combination of these strategies with chemotherapy in the first-line treatment. The CAIRO2 study evaluates the

  11. Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

    Directory of Open Access Journals (Sweden)

    V. Surmont

    2009-01-01

    Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

  12. Real-world Direct Health Care Costs for Metastatic Colorectal Cancer Patients Treated With Cetuximab or Bevacizumab-containing Regimens in First-line or First-line Through Second-line Therapy.

    Science.gov (United States)

    Johnston, Stephen; Wilson, Kathleen; Varker, Helen; Malangone-Monaco, Elisabetta; Juneau, Paul; Riehle, Ellen; Satram-Hoang, Sacha; Sommer, Nicolas; Ogale, Sarika

    2017-12-01

    The present study examined real-world direct health care costs for metastatic colorectal cancer (mCRC) patients initiating first-line (1L) bevacizumab (BEV)- or cetuximab (CET)-containing regimen in 1L or 1L-through-second-line (1L-2L) therapy. Using a large US insurance claims database, patients with mCRC initiating 1L BEV- or 1L CET-containing regimen from January 1, 2008 to September 30, 2014 were identified. The per-patient per-month (PPPM) all-cause health care costs (2014 US dollars) were measured during 1L therapy and, for patients continuing to a 2L biologic-containing regimen, 1L-2L therapy. Multivariable regression analyses were used to compare PPPM total health care costs between patients initiating a 1L BEV- versus 1L CET-containing regimen. A total of 6095 patients initiating a 1L BEV- and 453 initiating a 1L CET-containing regimen were evaluated for 1L costs; 2218 patients initiating a 1L BEV- and 134 initiating a 1L CET-containing regimen were evaluated for 1L-2L costs. In 1L therapy, 1L CET had adjusted PPPM costs that were $3135 (95% confidence interval [CI], $1174-$5040; P < .001) greater on average than 1L BEV. In 1L-2L therapy, 1L BEV-2L CET had adjusted PPPM costs that were $1402 (95% CI, $1365-$1442; P = .010) greater than those for 1L BEV-2L BEV, and 1L CET-2L BEV had adjusted PPPM costs that were $4279 (95% CI, $4167-$4400; P = .001) greater on average than those for 1L BEV-2L BEV. The adjusted PPPM cost differences for 1L BEV-2L other biologic or 1L CET-2L other biologic agent were numerically greater but statistically insignificant. PPPM total health care costs for 1L and 2L therapy tended to be greater for patients treated with 1L CET-containing regimens than for 1L BEV-containing regimens. Also, continuing treatment with BEV-containing regimens 1L-2L was less costly than switching between BEV and CET. The cost differences between BEV and CET hold important implications for treatment decisions of mCRC patients in real-world clinical

  13. [Correlation between Serum Tumor Markers and Efficacy of First-line EGFR-TKIs in Patients with Advanced Lung Adenocarcinoma].

    Science.gov (United States)

    Chen, Hanxiao; Yang, Xue; Liu, Huijun; Ma, Kun; Zhong, Jia; Dong, Zhi; Zhuo, Minglei; Wang, Yuyan; Li, Jianjie; An, Tongtong; Wu, Meina; Wang, Ziping; Zhao, Jun

    2017-09-20

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation. Limited to the standards of tumor tissue samples and detection methods, still some people can't receive target therapy following genetic guidance. This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs. We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation, who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital, analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs. The objective response rate (ORR) was 52.8% and the disease control rate (DCR) was 89.3%. The results showed that, patients with high CEA level before treatment responded better to TKIs (ORR 61.3% vs 35.9%, DCR 95.2% vs 74.4%, PCEA decreased 1 month later (61.5% vs 25%, P=0.002). Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo, P=0.027). To the opposite, PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo, P=0.029; 9.0 mo vs 11.5 mo, P=0.023, respectively). Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1, normal baseline CYFRA21-1 and CEA decline predicted longer PFS. The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo, P=0.003; 22.7 mo vs 55.0 mo, PCEA. High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma. While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.

  14. Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Li-li ZHANG

    2013-09-01

    Full Text Available Objective To investigate the therapeutic effects of Gemcitabine(GEM, Vinorelbine(NVB,Paclitaxel(TAX and other first-line chemotherapeutics plus platinum containing drugs on the elderly patients with advanced non-small cell lung cancer(NSCLC who had undergone surgery, and analyze the clinicopathological factors influencing the prognosis. Methods One hundred and seventeen advanced NSCLC patients aged 60 or over were treated with GP(GEM+platinum, or NP(NVB+platinum, or TP(TAX+platinum, or other first-line chemotherapeutics plus platinum(OCP after surgery, and their clinical data were then retrospectively studied to look for the relationship of patients' prognosis to clinicopathological factors(gender, operation methods, pathologicaltypes, differentiation, clinical stages.The survival curve was plotted with Kaplan-Meier method, hypothesis test was performed by log-rank, and the independent prognostic factors were screened with Cox proportional hazards regression model. Results Theone-, three- and five-year survival rates of the 117 patients were 47.23%,17.52% and 8.05%, respectively. The progression free survival(PFS of GP, NP, TP and OCP groups were 6.0, 5.2, 6.1 and5.5 months(P>0.05, respectively. The median progression free survival was 5.7 months. Univariate and multivariate analysis showed that the differentiated degrees and clinical stages of elderly NSCLC patients were the independent prognostic factors. Conclusions Clinicopathological factors(differentiated degree andclinical stages are closely related to one-, three- and five-year survival rates of advanced NSCLC in elderly patients who received treatment of first-line chemotherapeutics plus platinum. However, the efficacy ofGP, NP, TP or OCP shows no significant difference.

  15. Prediction of response to first-line chemotherapy with steamboat's imaging in lymphoma patients. A preliminary report

    International Nuclear Information System (INIS)

    Spyridonidis, T.; Apostolopoulos, D.; Giannakenas, C.; Xourgia, X.; Vasilakosa, P.; Frangos, S.; Matsouka, P.

    2004-01-01

    Full text: Sestamibi is a transport substrate for both Pgp and MRP, which are closely related to MDR (multidrug resistance), a significant factor for chemotherapy treatment failure in many cancer patients. Imaging with Tc99m-Sestamibi has been studied for predicting chemotherapy response mainly in breast and lung cancer. A few studies exist regarding lymphoma patients. In our study we included 24 consecutive lymphoma patients that were referred to our department for initial (before treatment) Ga-67 scan. All these patients were also imaged with Tc99m-Sestamibi in order to evaluate its prognostic value in predicting response to first-line chemotherapy. 20 mCi of Tc99m-Sestamibi was injected intravenously and planar images of the whole body were obtained at 15 min and 2 hours later. In 21/24 patients SPECT was performed in area of interest (most commonly in thorax) both in early and late imaging. Ratios of tumor average counts to background in early and late planar and SPECT images were calculated, also ratios of max tumor counts to background were calculated, as well as tumor washout rate. In all the estimations time decay correction was applied. A visual interpretation score was introduced for early uptake and another for Sestamibi retention in late images. Early uptake score was considered 0 in no or nearly no uptake, 1 in low uptake, 2 in moderate uptake, and 3 in high uptake. Tumor retention score was considered 0 in no retention (not or nearly not visible on late images), 1 in slight/moderate uptake (tumor better seen on early images), 2 in moderate uptake (tumor seen similar/somehow better in late images), 3 high retention (tumor definitely seen better on late images). Finally a total prognostic score (TPS) was derived by the sum of the two above-mentioned scores (uptake score plus retention score). The mean age of our patients was 48.8 ±13.9 years (range 17-80 years). 12 patients were men, and 12 women. There were 8 patients with HD and 16 with NHL. Three of

  16. Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma

    DEFF Research Database (Denmark)

    Maughan, Benjamin L; Agarwal, Neeraj; Hussain, Syed A

    2013-01-01

    Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC an...

  17. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients

    DEFF Research Database (Denmark)

    Wittkop, Linda; Arsandaux, Julie; Trevino, Ana

    2017-01-01

    Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations...

  18. Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis.

    Science.gov (United States)

    OuYang, Pu-Yun; Su, Zhen; Mao, Yan-Ping; Deng, Wuguo; Xie, Fang-Yun

    2013-01-01

    The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR = 0.81, 95% CI 0.69-0.95, P = 0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (Pchemotherapy (P = 0.02). In selected patients by EGFR-mutation, both mutation positive (HR = 0.48, 95% CI 0.28-0.83, P = 0.009) and negative (HR = 0.84, 95% CI 0.72-0.98, P = 0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P = 0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR = 0.51, 95% CI 0.35-0.74, P = 0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR = 2.01, 95% CI 1.11-3.63; P = 0.02) and diarrhea (RR = 2.70, 95% CI 1.94-3.76; Pchemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.

  19. Time since start of first-line therapy as a predictive clinical marker for nintedanib in patients with previously treated non-small cell lung cancer

    DEFF Research Database (Denmark)

    Gaschler-Markefski, Birgit; Sikken, Patricia; Heymach, John V

    2017-01-01

    INTRODUCTION: No predictive clinical or genetic markers have been identified or validated for antiangiogenic agents in lung cancer. We aimed to identify a predictive clinical marker of benefit for nintedanib, an angiokinase inhibitor, using data from two large second-line non-small cell lung cancer...... Phase III trials (LUME-Lung 1 ([LL1] and LUME-Lung 2). METHODS: Predictive marker identification was conducted in a multi-step process using data from both trials; a hypothesis was generated, confirmed and validated. Statistical analyses included a stepwise selection approach, a recursive partitioning...... method and the evaluation of HRs, including treatment-by-covariate interactions. The marker was finally validated using a prospectively defined hierarchical testing procedure and treatment-by-covariate interaction for overall survival (OS) based on LL1. RESULTS: Time since start of first-line therapy...

  20. Incidence and risk factors of major toxicity associated to first-line antituberculosis drugs for latent and active tuberculosis during a period of 10 years

    Directory of Open Access Journals (Sweden)

    Ana Tavares e Castro

    2015-05-01

    Full Text Available Introduction: Adverse drug reactions (ADR to first-line antituberculosis drugs are frequent and have important implications that may affect the effectiveness of treatment and course of tuberculosis (TB. Material and methods: Retrospective data analysis of clinical records and national registration forms from patients with ADR to first line antituberculosis that occurred between 2004 and 2013 at a Portuguese Pulmonology Diagnostic Centre, and from a case–control population matched by sex, age and year of initiation of treatment. Results: Of the 764 patients treated with antituberculosis drugs, 55 (52.7% male, 92.7% European, mean age 50.8 ± 19.5 years had at least one severe ADR and six had a second ADR, for a total of 61 events. The most frequent ADR were hepatotoxicity (86.9%, rash (8.2% and others, such as ocular toxicity, gastrointestinal intolerance and angioedema (4.9%. Isoniazid, alone or in combination, was the antituberculosis drug most associated to toxicity. Due to ADR, treatment time changed an average of 1.0 ± 2.6 months (range −3.4 to 10.6. There was no correlation between age or gender and the overall incidence of ADR although we found a significant association between younger age and an increased risk of hepatotoxicity (P = 0.035. There was also a statistically significant relationship between ADR and diabetes mellitus (P = 0.042 but not for other comorbidities or multi-resistant TB risk factors. Conclusions: This study found a high frequency of ADR with strong impact on subsequent therapeutic orientation. What seems to be of particular interest is the relationship between ADR and diabetes mellitus and the increased frequency of hepatotoxicity in younger patients. Keywords: Tuberculosis, Adverse reaction, Antituberculosis, Treatment

  1. On-Chip Dielectrophoretic Separation and Concentration of Viable, Non-Viable and Viable but Not Culturable (VBNC) Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Packard, M M; Shusteff, M; Alocilja, E C

    2012-04-12

    Although bacterial culture remains the gold standard for detection of viable bacteria in environmental specimens, the typical time requirement of twenty-four hours can delay and even jeopardize appropriate public health intervention. In addition, culture is incapable of detecting viable but not culturable (VBNC) species. Conversely, nucleic acid and antibody-based methods greatly decrease time to detection but rarely characterize viability of the bacteria detected. Through selection by membrane permeability, the method described in this work employs positive dielectrophoresis (pDEP) for separation and purification of viable and VBNC species from water and allows concentration of bacteria for downstream applications.

  2. Efficacy of daiokanzoto in chronic constipation refractory to first-line laxatives

    OpenAIRE

    Hirose, Tatsuya; Shinoda, Yasutaka; Yoshida, Aya; Kurimoto, Machiko; Mori, Kouki; Kawachi, Yuki; Tanaka, Kouji; Takeda, Atsuko; Yoshimura, Tomoaki; Sugiyama, Tadashi

    2016-01-01

    There are only a few treatment options for constipation and limited evidence of suitable treatments. Daiokanzoto (DKT) is a Kampo medicine often used clincally to treat constipation. DKT is a laxative used predominantly in Japan; however, clinical data on its efficacy and safety is lacking. Patients who used DKT, but were intolerant to either magnesium oxide (MgO; MgO group; n=16) or senna extract (Senna group; n=26) were included in the present study. The frequencies of their bowel movements...

  3. Efficacy of daiokanzoto in chronic constipation refractory to first-line laxatives.

    Science.gov (United States)

    Hirose, Tatsuya; Shinoda, Yasutaka; Yoshida, Aya; Kurimoto, Machiko; Mori, Kouki; Kawachi, Yuki; Tanaka, Kouji; Takeda, Atsuko; Yoshimura, Tomoaki; Sugiyama, Tadashi

    2016-10-01

    There are only a few treatment options for constipation and limited evidence of suitable treatments. Daiokanzoto (DKT) is a Kampo medicine often used clincally to treat constipation. DKT is a laxative used predominantly in Japan; however, clinical data on its efficacy and safety is lacking. Patients who used DKT, but were intolerant to either magnesium oxide (MgO; MgO group; n=16) or senna extract (Senna group; n=26) were included in the present study. The frequencies of their bowel movements were compared during the 1 week prior to and following DKT administration. Within 24 hours after DKT administration, 93.8% of the patients in the MgO group evacuated their bowels. The median bowel movement frequency 1 week prior to DKT administration was 2.5 and 1 week after DKT administration was significantly increased to 7.5. In the Senna group, within 24 h of DKT administration, 80.8% of the patients evacuated their bowels. The median bowel movement frequency 1 week prior to the DKT treatment was 2.0, which significantly increased to 8.5 1 week after the administration of DKT. The adverse events from DKT treatment were mild and controllable.

  4. Efficacy of daiokanzoto in chronic constipation refractory to first-line laxatives

    Science.gov (United States)

    Hirose, Tatsuya; Shinoda, Yasutaka; Yoshida, Aya; Kurimoto, Machiko; Mori, Kouki; Kawachi, Yuki; Tanaka, Kouji; Takeda, Atsuko; Yoshimura, Tomoaki; Sugiyama, Tadashi

    2016-01-01

    There are only a few treatment options for constipation and limited evidence of suitable treatments. Daiokanzoto (DKT) is a Kampo medicine often used clincally to treat constipation. DKT is a laxative used predominantly in Japan; however, clinical data on its efficacy and safety is lacking. Patients who used DKT, but were intolerant to either magnesium oxide (MgO; MgO group; n=16) or senna extract (Senna group; n=26) were included in the present study. The frequencies of their bowel movements were compared during the 1 week prior to and following DKT administration. Within 24 hours after DKT administration, 93.8% of the patients in the MgO group evacuated their bowels. The median bowel movement frequency 1 week prior to DKT administration was 2.5 and 1 week after DKT administration was significantly increased to 7.5. In the Senna group, within 24 h of DKT administration, 80.8% of the patients evacuated their bowels. The median bowel movement frequency 1 week prior to the DKT treatment was 2.0, which significantly increased to 8.5 1 week after the administration of DKT. The adverse events from DKT treatment were mild and controllable. PMID:27699020

  5. Resistance to first line platinum paclitaxel chemotherapy in serous epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Smoter, Marta; Waldstrøm, Marianne

    2014-01-01

    of sensitivity to platinum/paclitaxel treatment. The primary aim of the study was to investigate whether ERCC1 and Tau protein expression correlates with patient outcome in newly diagnosed epithelial ovarian cancer (EOC) patients. Formalin-fixed, paraffin-embedded tissue sections from 227 newly diagnosed EOC...

  6. The sensitivities to first-line antibiotic therapy of the common urinary ...

    African Journals Online (AJOL)

    Background: Urinary tract infections (UTIs) are among the most common human infections. Many urinary tract bacteria are capable of expressing drug resistance. Resistant bacteria may be present from the commencement of the infection or may develop during treatment. This study focused on the problem of antibiotic ...

  7. Liver enzyme elevations in a cohort of HIV/AIDS patients on first-line ...

    African Journals Online (AJOL)

    Introduction: All antiretroviral therapies (ARTs) are potentially toxic to the liver. In sub-Saharan Africa, the rising incidence of ART induced adverse events has complicated treatment leading to recent revisions of Namibian ART guidelines. Unfortunately there have been limited studies to date evaluating ART induced liver ...

  8. Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Frank, H.; Palshof, T.; Sørensen, Jens Benn

    2008-01-01

    The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0-2. Treatment was vinorelbine 25 mg m(-2) i.v. weekly and cisplatin 100...

  9. Rocuronium Versus Suxamethonium: A Survey of First-line Muscle Relaxant Use in UK Prehospital Rapid Sequence Induction.

    Science.gov (United States)

    Hartley, Emma L; Alcock, Roger

    2015-04-01

    Prehospital anaesthesia in the United Kingdom (UK) is provided by Helicopter Emergency Medical Service (HEMS) and British Association for Immediate Care (BASICS), a road-based service. Muscle relaxation in rapid sequence induction (RSI) has been traditionally undertaken with the use of suxamethonium; however, rocuronium at higher doses has comparable intubating conditions with fewer side effects. The aim of this survey was to establish how many prehospital services in the UK are now using rocuronium as first line in RSI. An online survey was constructed identifying choice of first-line muscle relaxant for RSI and emailed to lead clinicians for BASICS and HEMS services across the UK. If rocuronium was used, further questions regarding optimal dose, sugammadex, contraindications, and difference in intubating conditions were asked. A total of 29 full responses (93.5%) were obtained from 31 services contacted. Suxamethonium was used first line by 17 prehospital services (58.6%) and rocuronium by 12 (41.4%). In 11 services (91.7%), a dose of 1 mg/kg of rocuronium was used, and in one service, 1.2 mg/kg (8.3%) was used. No services using rocuronium carried sugammadex. In five services, slower relaxation time was found using rocuronium (41.7%), and in seven services, no difference in intubation conditions were noted (58.3%). Contraindications to rocuronium use included high probability of difficult airway and anaphylaxis. Use of rocuronium as first-line muscle relaxant in prehospital RSI is increasing. Continued auditing of practice will ascertain which services have adopted change and identify if complications of failed intubation increase as a result.

  10. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.

    Science.gov (United States)

    Vandenhende, Marie-Anne; Bellecave, Pantxika; Recordon-Pinson, Patricia; Reigadas, Sandrine; Bidet, Yannick; Bruyand, Mathias; Bonnet, Fabrice; Lazaro, Estibaliz; Neau, Didier; Fleury, Hervé; Dabis, François; Morlat, Philippe; Masquelier, Bernard

    2014-01-01

    Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs) is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS) before antiretroviral therapy (ART) and at virological failure (VF), in HIV-1 infected patients experiencing VF on first-line ART. Twenty-nine ART-naive patients followed up in the ANRS-CO3 Aquitaine Cohort, having initiated ART between 2000 and 2009 and experiencing VF (2 plasma viral loads (VL) >500 copies/ml or one VL >1000 copies/ml) were included. Reverse transcriptase and protease DRMs were identified using Sanger sequencing (SS) and UDS at baseline (before ART initiation) and VF. Additional low-frequency variants with PI-, NNRTI- and NRTI-DRMs were found by UDS at baseline and VF, significantly increasing the number of detected DRMs by 1.35 fold (plow-frequency DRMs modified ARV susceptibility predictions to the prescribed treatment for 1 patient at baseline, in whom low-frequency DRM was found at high frequency at VF, and 6 patients at VF. DRMs found at VF were rarely detected as low-frequency DRMs prior to treatment. The rare low-frequency NNRTI- and NRTI-DRMs detected at baseline that correlated with the prescribed treatment were most often found at high-frequency at VF. Low frequency DRMs detected before ART initiation and at VF in patients experiencing VF on first-line ART can increase the overall burden of resistance to PI, NRTI and NNRTI.

  11. Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Höhler Thomas

    2004-07-01

    Full Text Available Abstract Background Combination therapy of irinotecan, folinic acid (FA and 5-fluorouracil (5-FU has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases. Methods A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m2, L-FA (200 mg/m2 and 5-FU bolus (400 mg/m2 on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m2. One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients. Results The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%. Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%, nausea/vomiting (12%, leucopenia (3%, neutropenia (9% and mucositis (3%. The overall response rate was 31% (4 CR and 7 PR, with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively. Conclusions The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant

  12. First-line chemotherapy in low-risk gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-01-01

    This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.

  13. Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

    International Nuclear Information System (INIS)

    Griffiths, R. I.; Gleeson, M. L.; Danese, M. D.; Griffiths, R. I.; Mikhael, J.

    2012-01-01

    Rituximab improves survival in follicular lymphoma (FL), but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER) registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P)) or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years), 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI) $9,302-$28,643) and longer adjusted cumulative survival (0.18 years; 95% CI 0.10-0.27) over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531-296,337) per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

  14. Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

    Directory of Open Access Journals (Sweden)

    Robert I. Griffiths

    2012-01-01

    Full Text Available Rituximab improves survival in follicular lymphoma (FL, but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C, doxorubicin, vincristine (V, and prednisone (P or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years, 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI $9,302–$28,643 and longer adjusted cumulative survival (0.18 years; 95% CI 0.10–0.27 over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531–296,337 per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

  15. Tumor markers cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen for monitoring metastatic breast cancer during first-line chemotherapy and follow-up

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1996-01-01

    progressive disease, the median positive lead time was 35 days during therapy and 76 days during follow-up. Tumor marker assessment may document that a therapy is effective and ought to be continued in spite of adverse toxic effects, and that a treatment is ineffective and should be stopped to prevent......We investigated whether model systems integrating stochastic variation into criteria for marker assessment could be used for monitoring metastatic breast cancer. A total of 3989 serum samples was obtained from 204 patients receiving first-line chemotherapy and from 112 of these patients during...... follow-up. Each sample was analyzed for cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen. The efficiency for identifying progression and nonprogression was 94% during therapy and 85% during follow-up, with no false-positive marker results for progressive disease. At clinical...

  16. CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer.

    Science.gov (United States)

    Gillison, Maura L; Blumenschein, George; Fayette, Jerome; Guigay, Joel; Colevas, A Dimitrios; Licitra, Lisa; Harrington, Kevin J; Kasper, Stefan; Vokes, Everett E; Even, Caroline; Worden, Francis; Saba, Nabil F; Iglesias Docampo, Lara Carmen; Haddad, Robert; Rordorf, Tamara; Kiyota, Naomi; Tahara, Makoto; Monga, Manish; Lynch, Mark; Li, Li; Ferris, Robert L

    2018-06-04

    Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow-up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first-line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting. The Oncologist 2018. © AlphaMed Press 2018.

  17. Strengthening Agricultural Research Capacity for Viable Extension ...

    African Journals Online (AJOL)

    Strengthening Agricultural Research Capacity for Viable Extension Policies in Nigeria: An Exploration of Ricoeur's Hermeneutic Theory for Analysing Extension Research. ... Progressively more, researchers use hermeneutic philosophy to inform the conduct of interpretive research. Analogy between the philosophical ...

  18. Tibia Shaft Fractures in Adolescents: How and When Can They be Managed Successfully With Cast Treatment?

    Science.gov (United States)

    Ho, Christine A

    2016-06-01

    Despite the increasing popularity of operative treatment in adolescent tibia fractures, casting remains a viable first-line treatment. Because the selection bias in published reports does not allow direct comparison between casting and flexible nail treatment of closed pediatric tibia fractures, it is unclear whether flexible nailing offers any advantages over casting. This overview discusses parameters of acceptable alignment, indications, techniques for successful reduction and casting, subsequent inpatient and outpatient management including wedging of casted tibia fractures, expected outcomes, and comparison of casting with flexible nailing. As with any orthopaedic procedure, careful attention to patient selection, indications, and detail facilitates successful cast treatment in this older pediatric population.

  19. Evaluation of the efficacy of valproic acid and suberoylanilide hydroxamic acid (vorinostat in enhancing the effects of first-line tuberculosis drugs against intracellular Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Martin Rao

    2018-04-01

    Full Text Available Background: New tuberculosis (TB drug treatment regimens are urgently needed. This study evaluated the potential of the histone deacetylase inhibitors (HDIs valproic acid (VPA and suberoylanilide hydroxamic acid (SAHA to enhance the effects of first-line anti-TB drugs against intracellular Mycobacterium tuberculosis. Methods: M. tuberculosis H37Rv cultures were exposed to VPA or SAHA over 6 days, in the presence or absence of isoniazid (INH and rifampicin (RIF. The efficacy of VPA and SAHA against intracellular M. tuberculosis with and without INH or RIF was tested by treating infected macrophages. Bactericidal activity was assessed by counting mycobacterial colony-forming units (CFU. Results: VPA treatment exhibited superior bactericidal activity to SAHA (2-log CFU reduction, while both HDIs moderately improved the activity of RIF against extracellular M. tuberculosis. The bactericidal effect of VPA against intracellular M. tuberculosis was greater than that of SAHA (1-log CFU reduction and equalled that of INH (1.5-log CFU reduction. INH/RIF and VPA/SAHA combination treatment inhibited intracellular M. tuberculosis survival in a shorter time span than monotherapy (3 days vs. 6 days. Conclusions: VPA and SAHA have adjunctive potential to World Health Organization-recommended TB treatment regimens. Clinical evaluation of the two drugs with regard to reducing the treatment duration and improving treatment outcomes in TB is warranted. Keywords: Mycobacterium tuberculosis, Adjunct host-directed therapy, Tuberculosis, Histone deacetylase inhibitors, Repurposed drugs

  20. Recombinant FSH Compared to Clomiphene Citrate as the First-Line in Ovulation Induction in Polycystic Ovary Syndrome Using Newly Designed Pens: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Batool Hossein-Rashidi

    2016-05-01

    Full Text Available Objective: Since there is still controversy regarding the best first-line choice for ovulation induction (OI other than clomiphene citrate (CC in infertile women diagnosed with polycystic ovary syndrome (PCOS, the aim of the present study was to compare recombinant human FSH with CC as the first course of OI in these women.Materials and methods: In this pilot randomized controlled trial, 104 infertile women diagnosed with PCOS were randomized in two groups to receive either CC with the dose of 100mg per day from day 3 of a spontaneous or progestin-induced menstruation for 5 days or rFSH with the starting dose of 50 IU daily {and weekly dose increment of as low as 12.5 IU}, on the day4 of the cycle. They were assessed during a single OI course. The pregnancy rate (PR and live birth rate (LBR were the primary outcomes. The follicular response, endometrial thickness, cancellation of the cycles and ovarian hyper stimulation (OHSS rate were the secondary outcomes.Results: Analyzing data of 96 patients using Chi2 and Fischer’s Exact test (44 in rFSH group and 52 in CC group, both PR and LBR were comparable in the two groups {13.6% vs. 9.6% and 11.4% vs. 9.6% respectively}, with the difference not to be significant (p > 0.05. No cases of OHSS or multiple gestations happened during the treatment course.Conclusion: It seems that rFSH is as efficacious as CC while not with more complications for the first-line OI in infertile women with PCOS. However, due to the limitations of the present study including the small population and the single cycle of treatment, our results did not come out to prove this and more studies with larger study population are needed to compare the cumulative PR and LBR.

  1. Cost-effectiveness analysis of EGFR mutation testing and gefitinib as first-line therapy for non-small cell lung cancer.

    Science.gov (United States)

    Narita, Yusuke; Matsushima, Yukiko; Shiroiwa, Takeru; Chiba, Koji; Nakanishi, Yoichi; Kurokawa, Tatsuo; Urushihara, Hisashi

    2015-10-01

    The combination use of gefitinib and epidermal growth factor receptor (EGFR) testing is a standard first-line therapy for patients with non-small cell lung cancer (NSCLC). Here, we examined the cost-effectiveness of this approach in Japan. Our analysis compared the 'EGFR testing strategy', in which EGFR mutation testing was performed before treatment and patients with EGFR mutations received gefitinib while those without mutations received standard chemotherapy, to the 'no-testing strategy,' in which genetic testing was not conducted and all patients were treated with standard chemotherapy. A three-state Markov model was constructed to predict expected costs and outcomes for each strategy. We included only direct medical costs from the healthcare payer's perspective. Outcomes in the model were based on those reported in the Iressa Pan-Asia Study (IPASS). The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life-years (QALYs) gained. Sensitivity and scenario analyses were conducted. The incremental cost and effectiveness per patient of the 'EGFR testing strategy' compared to the 'no-testing strategy' was estimated to be approximately JP¥122,000 (US$1180; US$1=JP¥104 as of February 2014) and 0.036 QALYs. The ICER was then calculated to be around JP¥3.38 million (US$32,500) per QALY gained. These results suggest that the 'EGFR testing strategy' is cost-effective compared with the 'no-testing strategy' when JP¥5.0 million to 6.0 million per QALY gained is considered an acceptable threshold. These results were supported by the sensitivity and scenario analyses. The combination use of gefitinib and EGFR testing can be considered a cost-effective first-line therapy compared to chemotherapy such as carboplatin-paclitaxel for the treatment for NSCLC in Japan. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  2. A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany.

    Science.gov (United States)

    Watt, Maureen; McCrea, Charles; Johal, Sukhvinder; Posnett, John; Nazir, Jameel

    2016-10-01

    Clostridium difficile infection (CDI) represents a significant economic healthcare burden, especially the cost of recurrent disease. Fidaxomicin produced significantly lower recurrence rates and higher sustained cure rates in clinical trials. We evaluated the cost-effectiveness and budget impact of fidaxomicin compared with vancomycin in Germany in the first-line treatment of patient subgroups with CDI at increased risk of recurrence. A semi-Markov model was used to compare the cost-effectiveness and budget impact of fidaxomicin vs. vancomycin from a payer perspective in Germany. The model cycle length was 10 days. The time horizon was 1 year. Model inputs were probability of clinical cure, 30-day probability of recurrence, and 30-day attributable mortality based on evidence from two randomized controlled trials comparing fidaxomicin and vancomycin in patients with CDI. Cost-effectiveness outcomes were cost per quality-adjusted life year gained, cost per bed-day saved, and cost per recurrence avoided. Despite higher drug acquisition costs, fidaxomicin was dominant in the cancer subgroup (less costly and more effective) and cost-effective in the other subgroups, with incremental cost-effectiveness ratios vs. vancomycin ranging from €26,900 to €44,500. Hospitalization costs of the first-line treatment of CDI with fidaxomicin vs. vancomycin were lower in every patient subgroup, resulting in budget impacts ranging from -€1325 (in patients ≥65 years) to -€2438 (in cancer patients). Reductions in the cost of treating recurrence with fidaxomicin ranged from -€574.32 per patient in those receiving concomitant antibiotics to -€1500.68 per patient in renally impaired patients. In patient subgroups with CDI at increased recurrence risk, fidaxomicin was cost-effective vs. vancomycin, and less costly and more effective in patients with cancer.

  3. Characteristics influencing therapy switch behavior after suboptimal response to first-line treatment in patients with multiple sclerosis.

    Science.gov (United States)

    Teter, Barbara; Agashivala, Neetu; Kavak, Katelyn; Chouhfeh, Lynn; Hashmonay, Ron; Weinstock-Guttman, Bianca

    2014-06-01

    Factors driving disease-modifying therapy (DMT) switch behavior are not well understood. The objective of this paper is to identify patient characteristics and clinical events predictive of therapy switching in patients with suboptimal response to DMT. This retrospective study analyzed patients with relapsing-remitting multiple sclerosis (MS) and a suboptimal response to initial therapy with either interferon β or glatiramer acetate. Suboptimal responders were defined as patients with ≥1 MS event (clinical relapse, worsening disability, or MRI worsening) while on DMT. Switchers were defined as those who changed DMT within six to 12 months after the MS event. Of 606 suboptimal responders, 214 (35.3%) switched therapy. Switchers were younger at symptom onset (p = 0.012), MS diagnosis (p = 0.004), DMT initiation (p < 0.001), and first MS event (p = 0.011) compared with nonswitchers. Compared with one relapse alone, MRI worsening alone most strongly predicted switch behavior (odds ratio 6.3; 95% CI, 3.1-12.9; p < 0.001), followed by ≥2 relapses (2.8; 95% CI, 1.1-7.3; p = 0.040), EDSS plus MRI worsening (2.5; 95% CI, 1.1-5.9; p = 0.031) and EDSS worsening alone (2.2; 95% CI, 1.2-4.1; p = 0.009). Younger patients with disease activity, especially MRI changes, are more likely to have their therapy switched sooner than patients who are older at the time of MS diagnosis and DMT initiation. © The Author(s) 2013.

  4. Maintenance Therapy With Cetuximab Every Second Week in the First-Line Treatment of Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Pfeiffer, Per; Sorbye, Hafdan; Qvortrup, Camilla

    2015-01-01

    Group performance status of 0 to 2. Patients received 8 courses of Nordic FLOX (oxaliplatin 85 mg/m(2) over 1 hour on day 1, and 5-fluorouracil 500 mg/m(2) as a bolus injection, followed 30 minutes later with bolus folinic acid 60 mg/m(2) on days 1 and 2). Cetuximab was administered every 2 weeks...

  5. Multicenter pilot study of radio-chemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)

    DEFF Research Database (Denmark)

    Dagmar, Dagmar; Proescholdt, Martin; Reinert, Christiane

    2018-01-01

    Background: Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radio-chemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptiv...

  6. Comparison of FOLFOX and DOF regimens as first-line treatment in East Asian patients with advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu M

    2018-01-01

    Full Text Available Mengyao Liu,1,2 Guofang Hu,2 Yuan Wang,2 Jun Guo,2 Liyan Liu,2 Xiao Han,2 Zhehai Wang2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, 2Department of Oncology, Shandong Cancer Hospital, affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China Background: Our study retrospectively assesses the safety and efficacy of the FOLFOX (oxaliplatin, fluorouracil, and leucovorin versus DOF (docetaxel, oxaliplatin, and fluorouracil regimens in untreated locally advanced gastric cancer (AGC.Patients and methods: A total of 108 patients underwent DOF (N=58 and FOLFOX (N=50 regimens. The end points were overall response rate (ORR, survival, and toxicity. Kaplan–Meier curve was used to estimate overall survival (OS and progression-free survival (PFS and Cox regression for multivariate analysis.Results: The ORRs were 50% for DOF and 30% for FOLFOX groups (P<0.05, and disease control rates were 91.4% and 72%, respectively. The median PFS and OS in DOF group were significantly better than FOLFOX group (8.2 versus 6.4 months, P<0.05; 16.3 versus 11.2 months, P<0.001. Both groups showed acceptable toxicity; all grades and grade 3–4 toxicity had no significant differences (P=0.071; P=0.247. However, the incidence of grade 3–4 peripheral neuropathy was significantly higher in DOF group (10.3% versus 2%, P<0.05. In the subgroup analysis for elderly AGC patients (≥65 years, administration of DOF also resulted in a superior PFS (8.5 versus 5.9 months; P=0.038 and OS (15.3 versus 9.8 months; P=0.004 compared with FOLFOX. However, DOF regimen was associated with more neutropenia (67% versus 30%; P<0.05, thrombocytopenia (61% versus 52%; P<0.05, and peripheral neuropathy (49% versus 22%; P<0.05.Conclusion: DOF regimen was more effective than FOLFOX for AGC, both in younger and older patients. The adverse effects of the two regimens were manageable. The combination of docetaxel/oxaliplatin/fluorouracil was active and well tolerated in AGC patients and deserves further evaluation. However, for elderly patients with AGC, the DOF regimen was associated with worse toxicities; therefore, the FOLFOX regimen might be a more suitable option. Keywords: East Asian AGC patients, chemotherapy, safety, efficacy

  7. First-line antituberculosis drug, pyrazinamide, its pharmaceutically relevant cocrystals and a salt.

    Science.gov (United States)

    Sarmah, Kashyap Kumar; Rajbongshi, Trishna; Bhowmick, Sourav; Thakuria, Ranjit

    2017-10-01

    A few pyrazinamide (Pyz) cocrystals involving hydroxybenzoic/cinnamic acid derivatives [2,4-dihydroxybenzoic acid (24DHBA); 2,6-dihydroxybenzoic acid (26DHBA); 3,5-dihydroxybenzoic acid (35DHBA) and nutraceutical molecule ferulic acid (FRA)] and the first example of a molecular salt with p-toluenesulfonic acid (pTSA) have been prepared and characterized using various solid-state techniques. A high-temperature cocrystal polymorph of Pyz·FRA has been characterized from the endothermic peaks observed using differential scanning calorimetry. The presence of substituent groups carrying hydrogen bond donors or acceptors and their influence on supramolecular synthon formation has been investigated using a Cambridge Structural Database search. Equilibrium solubility of all the binary complexes of Pyz follows the order of their coformer solubility, i.e. Pyz + ·pTSA - > Pyz·35DHBA > Pyz > Pyz·26DHBA > Pyz·24DHBA > Pyz·FRA. A twofold enhancement in solubility of Pyz + ·pTSA - molecular salt compared with the parent drug suggests a potential drug formulation for the treatment of tuberculosis.

  8. Is imatinib still the best choice as first-line oral TKI

    Directory of Open Access Journals (Sweden)

    Shweta Bansal

    2014-01-01

    Full Text Available Targeted therapy is the buzz word these days. A decade back the emergence of tyrosine kinase inhibitor Imatinib on the horizon, as the targeted therapy, had captured the imagination of everyone in the field of cancer. It is encouraging to see a large number of patients getting relief from deadly CML disease and leading a good quality of life with the help of this drug. However, sky is not the limit and now we have second and third generation tyrosine kinase inhibitors. I still remember the sagacious smile on the face of late Dr. John Goldman, when I asked him about his preferred choice and he replied and I quote "this is going to be the debate of the decade." Here I take the opportunity to contribute to this debate. I have scrutinized various aspects of the three TKIs, now recommended, for the treatment of CML. I`m still convinced it is too early to shift our practice completely towards 2G TKI as more time is required to make a clear recommendation.

  9. Tumor markers CEA and CA 19-9 correlate with radiological imaging in metastatic colorectal cancer patients receiving first-line chemotherapy.

    Science.gov (United States)

    Michl, M; Koch, J; Laubender, R P; Modest, D P; Giessen, C; Schulz, Ch; Heinemann, V

    2014-10-01

    In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), γ-glutamyltransferase (γGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27-85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes (n = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) (p = 0.005) and between PD and stable disease (SD) (p = 0.042). CA 19-9 level slopes (n = 57; slopes = 127) also showed a significant difference between PD and PR (p = 0.002) and PD and SD (p = 0.058). Furthermore, CRP slopes (n = 62; slopes = 134) differed significantly between PD and PR (p = 0.009). For LDH, ALP, γGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in

  10. Prognostic risk stratification derived from individual patient level data for men with advanced penile squamous cell carcinoma receiving first-line systemic therapy.

    Science.gov (United States)

    Pond, Gregory R; Di Lorenzo, Giuseppe; Necchi, Andrea; Eigl, Bernhard J; Kolinsky, Michael P; Chacko, Raju T; Dorff, Tanya B; Harshman, Lauren C; Milowsky, Matthew I; Lee, Richard J; Galsky, Matthew D; Federico, Piera; Bolger, Graeme; DeShazo, Mollie; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru

    2014-05-01

    Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (Pstatistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including

  11. Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database.

    Science.gov (United States)

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T; Adams, Richard; Saltz, Leonard; Goldberg, Richard M; Punt, Cornelis J A; Douillard, Jean-Yves; Hoff, Paulo M; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J

    2015-01-01

    Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. © 2014 by American Society of Clinical Oncology.

  12. [The impact of ascorbic acid on the concentrations of antioxidative vitamins in the plasma of patients with non-small cell lung cancer undergoing first-line chemotherapy].

    Science.gov (United States)

    Tokarski, Sławomir; Rutkowski, Maciej; Godala, Małgorzata; Mejer, Anna; Kowalski, Jan

    2013-09-01

    One of the main after-effects of chemotherapy used in cancer treatment is an augmented production of reactive oxygen species (ROS). In turn ROS become a source of unwanted side effects of chemotherapy, often forcing the discontinuation of the therapy. Ascorbic acid (vitamin C), being an antioxidant, can strengthen the antioxidative barrier of an organism. The aim of the study was an assessment of the concentrations of A, C and E vitamins in the plasma of NSCLC patients undergoing chemotherapy supplemented with vitamin C. 25 first-line chemotherapy patients with inoperable NSCLC, including 19 men and 6 women aged between 37-73 years (average age 60.1 +/- 8.8 years) have undergone the examination. Their chemotherapy has been supplemented with ascorbic acid (vitamin C dose of 600 mg per 24 hours). Control group consisted of 24 healthy individuals, including 18 men and 6 women aged between 49-71 years (average age 59.5 +/- 6.6 years). In cancer patients the concentration of A, C and E vitamins was assessed by spectrophotometry using T60V spectrophotometer (PG Instruments) before and after first-line chemotherapy which was supplemented with vitamin C. In control group the concentrations of antioxidative vitamins was assessed only once. In comparison to the control group the concentrations of the A, C and E vitamins in the plasma of NSCLC patients was significantly lower (p vitamin C a significant rise of concentrations (p vitamins tested for was observed. The biggest rise was noted for vitamin C (99.8%). The supplementation of the chemotherapy of NSCLC patients with C vitamin leads to rise of the low concentrations of A, C and E vitamins in the plasma. This suggests strengthening of the antioxidative barrier in patients.

  13. Feasibility and clinical value of CT-guided {sup 125}I brachytherapy for metastatic soft tissue sarcoma after first-line chemotherapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Mo, Zhiqiang; Zhang, Yanling; Xiang, Zhanwang; Yan, Huzhen; Zhong, Zhihui; Gao, Fei; Zhang, Fujun [Sun Yat-Sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou (China); Zhang, Tao [Guangzhou Medical University, Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children' s Medical Centre, Guangzhou (China)

    2018-03-15

    To evaluate the feasibility and usefulness of computed tomography (CT)-guided iodine{sup 125} ({sup 125}I) brachytherapy for patients with metastatic soft tissue sarcoma (STS) after first-line chemotherapy failure. We recruited 93 patients with metastatic STS who had received first-line chemotherapy 4-6 times but developed progressive disease, from January 2010 to July 2015; 45 patients who had combined {sup 125}I brachytherapy and second-line chemotherapy (Group A), and 48 patients who received second-line CT only (Group B). In Group A, 49 {sup 125}I seed implantation procedures were performed in 45 patients with 116 metastatic lesions; the primary success rate was 91.1% (41/45), without life-threatening complications. Local control rates at 3, 6, 12, 24 and 36 months were 71.1%, 62.2%, 46.7%, 28.9% and 11.1% for Group A, and 72.9%, 54.2%, 18.8%, 6.3% and 0% for Group B. Mean progression-free survival differed significantly (Group A: 7.1±1.3 months; Group B: 3.6 ±1.1 months; P<0.001; Cox proportional hazards regression analysis), but overall survival did not significantly differ (Group A: 16.9 ±5.1 months; Group B: 12.1 ± 4.8 months). Group A showed better symptom relief and quality of life than Group B. CT-guided {sup 125}I brachytherapy is a feasible and valuable treatment for patients with metastatic STS. (orig.)

  14. Cost-effectiveness-analysis: radioiodine or antithyroid drugs as first-line therapy of hyperthyroidism due to Graves' disease

    International Nuclear Information System (INIS)

    Dietlein, M.; Moka, D.; Dederichs, B.; Schicha, H.; Hunsche, E.; Lauterbach, K.W.

    1999-01-01

    Aim: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines. Method: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq I-131 residual activity. Result: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs. Conclusion: Radioiodine is a cost-effective, first-line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor-antibodies or Tc-uptake). (orig.) [de

  15. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    DEFF Research Database (Denmark)

    Felip, E; Gridelli, C; Baas, P

    2011-01-01

    the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...... at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement on three of these areas: NSCLC pathology and molecular testing, the treatment of first-line...

  16. Sycamore produces viable seed after six years

    Science.gov (United States)

    A. F. Ike

    1966-01-01

    In the early stages of any tree improvement program it is desirable to know how soon progenies of selected parents can themselves be included in a breeding program. How soon will they produce viable pollen and seed? In the case of sycamore (Platanus occidentalis L.), the information is meager: the Woody- Plant Seed Manual lists the minimum commercial seedbearing age...

  17. Factors associated with recent unsuppressed viral load in HIV-1-infected patients in care on first-line antiretroviral therapy in South Africa.

    Science.gov (United States)

    Joseph Davey, D; Abrahams, Z; Feinberg, M; Prins, M; Serrao, C; Medeossi, B; Darkoh, E

    2018-05-01

    Unsuppressed viral load (VL) in patients on antiretroviral therapy (ART) occurs when treatment fails to suppress a person's VL and is associated with decreased survival and increased HIV transmission. The objective of this study was to evaluate factors associated with unsuppressed VL (VL > 400 copies/ml) in patients currently in care on first-line ART for ≥ 6 months attending South African public healthcare facilities. We analysed electronic medical records of ART patients with a VL result on record who started ART between January 2004 and April 2016 from 271 public health facilities. We present descriptive and multivariable logistic regression for unsuppressed VL at last visit using a priori variables. We included 244,370 patients (69% female) on first-line ART in April 2016 for ≥ 6 months. Median age at ART start was 33 years (7% were < 15 years old). Median duration on ART was 3.7 years. Adjusting for other variables, factors associated with having an unsuppressed VL at the most recent visit among patients in care included: (1) < 15 years old at ART start (adjusted odds ratio [aOR]=2.58; 95% CI = 2.37, 2.81) versus 15-49 years at ART start, (2) male gender (aOR = 1.29; 95% CI = 1.25, 1.35), (3) 6-12 months on ART versus longer (aOR = 1.34; 95% CI = 1.29, 1.40), (4) on tuberculosis (TB) treatment (aOR = 1.78; 95% CI = 1.48, 2.13), and (5) prior ART exposure versus none (aOR = 1.20; 95% CI = 1.08, 1.32). Approximately 85% of the ART cohort who were in care had achieved viral suppression, though men, youth/adolescents, patients with prior ART exposure, those with short duration of ART, and patients on TB treatment had increased odds of not achieving viral suppression. There is a need to develop and evaluate targeted interventions for ART patients in care who are at high risk of unsuppressed VL.

  18. Is Atherectomy the Best First-Line Therapy for Limb Salvage in Patients With Critical Limb Ischemia?

    Science.gov (United States)

    Loor, Gabriel; Skelly, Christopher L.; Wahlgren, Carl-Magnus; Bassiouny, Hisham S.; Piano, Giancarlo; Shaalan, Wael

    2010-01-01

    Objective To determine the efficacy of atherectomy for limb salvage compared with open bypass in patients with critical limb ischemia. Methods Ninety-nine consecutive bypass and atherectomy procedures performed for critical limb ischemia between January 2003 and October 2006 were reviewed. Results A total of 99 cases involving TASC C (n = 43, 44%) and D (n = 56, 56%) lesions were treated with surgical bypass in 59 patients and atherectomy in 33 patients. Bypass and atherectomy achieved similar 1-year primary patency (64% vs 63%; P = .2). However, the 1-year limb salvage rate was greater in the bypass group (87% vs 69%; P = .004). In the tissue loss subgroup, there was a greater limb salvage rate for bypass patients versus atherectomy (79% vs 60%; P = .04). Conclusions Patients with critical limb ischemia may do better with open bypass compared with atherectomy as first-line therapy for limb salvage. PMID:19640919

  19. Managerial competencies among first-line newsroom managers at small to medium-sized mainstream media enterprises in South Africa

    Directory of Open Access Journals (Sweden)

    Elanie Steyn

    2014-06-01

    Full Text Available Changes in the South African media and management environment have had distinct influences on especially small to medium-sized mainstream media enterprises (media SMEs which often have to compete with bigger media organisations for the same news stories. Moreover, these media organisations are commonly faced with unique challenges related to human and other resources. This situation adds to the importance of effective and efficient management practices at these media sites. The management practices of first-line news managers in media SMEs are qualitatively and quantitatively evaluated in this paper by considering six managerial competencies found in general management theory. These competencies relate to communication, planning and administration, teamwork; strategic action, global awareness and self-management.

  20. Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab: RESULTS from the NORDIC VII Study.

    Directory of Open Access Journals (Sweden)

    Line S Tarpgaard

    Full Text Available We aim to test the hypothesis that high plasma YKL-40 is associated with short progression-free survival (PFS and overall survival (OS in patients with metastatic colorectal cancer (mCRC treated with first-line oxaliplatin and 5-flourouracil with or without cetuximab.A total of 566 patients in the NORDIC VII Study were randomized 1∶1∶1 to arm A (Nordic FLOX, arm B (Nordic FLOX + cetuximab, or arm C (Nordic FLOX + cetuximab for 16 weeks followed by cetuximab alone as maintenance therapy. Pretreatment plasma samples were available from 510 patients. Plasma YKL-40 was determined by ELISA and dichotomized according to the age-corrected 95% YKL-40 level in 3130 healthy subjects.Pretreatment plasma YKL-40 was elevated in 204 patients (40%, and median YKL-40 was higher in patients with mCRC than in healthy subjects (age adjusted, P<0.001. Patients with elevated YKL-40 had shorter PFS than patients with normal YKL-40 (7.5 vs. 8.2 months; hazard ratio (HR  = 1.27 95% confidence interval (CI 1.05-1.53 P = 0.013 and shorter OS (16.8 vs. 23.9 months; HR = 1.33, 1.04-1.69, P = 0.024. Multivariate Cox analysis demonstrated that elevated pretreatment YKL-40 was an independent biomarker of short OS (HR = 1.12, 1.01-1.25, P = 0.033. The ratio of the updated plasma YKL-40 (i.e. level after 1, 2, 8 weeks of treatment, and at end of treatment compared to the baseline level was associated with OS (HR = 1.27, 1.06-1.52, P = 0.011.Plasma YKL-40 is an independent prognostic biomarker in patients with mCRC treated with first-line oxaliplatin-based therapy alone or combined with cetuximab.

  1. Immediate natural tooth pontic: A viable yet temporary prosthetic solution: A patient reported outcome

    Directory of Open Access Journals (Sweden)

    Sudhir Bhandari

    2012-01-01

    Conclusion: The concept of immediate pontic placement is surely a viable treatment option and promises an excellent transient esthetic solution for a lost tooth as well as enables good preparation of the extraction site for future prosthetic replacement.

  2. Monotone viable trajectories for functional differential inclusions

    Science.gov (United States)

    Haddad, Georges

    This paper is a study on functional differential inclusions with memory which represent the multivalued version of retarded functional differential equations. The main result gives a necessary and sufficient equations. The main result gives a necessary and sufficient condition ensuring the existence of viable trajectories; that means trajectories remaining in a given nonempty closed convex set defined by given constraints the system must satisfy to be viable. Some motivations for this paper can be found in control theory where F( t, φ) = { f( t, φ, u)} uɛU is the set of possible velocities of the system at time t, depending on the past history represented by the function φ and on a control u ranging over a set U of controls. Other motivations can be found in planning procedures in microeconomics and in biological evolutions where problems with memory do effectively appear in a multivalued version. All these models require viability constraints represented by a closed convex set.

  3. Regulation of Viable and Optimal Cohorts

    Energy Technology Data Exchange (ETDEWEB)

    Aubin, Jean-Pierre, E-mail: aubin.jp@gmail.com [VIMADES (Viabilité, Marchés, Automatique, Décisions) (France)

    2015-10-15

    This study deals with the evolution of (scalar) attributes (resources or income in evolutionary demography or economics, position in traffic management, etc.) of a population of “mobiles” (economic agents, vehicles, etc.). The set of mobiles sharing the same attributes is regarded as an instantaneous cohort described by the number of its elements. The union of instantaneous cohorts during a mobile window between two attributes is a cohort. Given a measure defining the number of instantaneous cohorts, the accumulation of the mobile attributes on a evolving mobile window is the measure of the cohort on this temporal mobile window. Imposing accumulation constraints and departure conditions, this study is devoted to the regulation of the evolutions of the attributes which are1.viable in the sense that the accumulations constraints are satisfied at each instant;2.and, among them, optimal, in the sense that both the duration of the temporal mobile window is maximum and that the accumulation on this temporal mobile window is the largest viable one. This value is the “accumulation valuation” function. Viable and optimal evolutions under accumulation constraints are regulated by an “implicit Volterra integro-differential inclusion” built from the accumulation valuation function, solution to an Hamilton–Jacobi–Bellman partial differential equation under constraints which is constructed for this purpose.

  4. A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

    Directory of Open Access Journals (Sweden)

    Glen J Weiss

    Full Text Available Small cell lung cancer (SCLC that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients.Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50% received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration. The remaining patients had clinical deterioration before NGS recommended therapy could be initiated.Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

  5. A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

    Science.gov (United States)

    Weiss, Glen J; Byron, Sara A; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A; Carpten, John D; Craig, David W; Whitsett, Timothy G

    2017-01-01

    Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

  6. Emerging Trends of HIV Drug Resistance in Chinese HIV-Infected Patients Receiving First-Line Highly Active Antiretroviral Therapy: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Liu, Huixin; Ma, Ye; Su, Yingying; Smith, M. Kumi; Liu, Ying; Jin, Yantao; Gu, Hongqiu; Wu, Jing; Zhu, Lin; Wang, Ning

    2014-01-01

    Background. Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human immunodeficiency virus (HIV) replication and reconstitution of the immune response. Settings like China that experienced rapid HAART rollout and relatively limited drug selection face considerable challenges in controlling HIV drug resistance (DR). Methods. We conducted a systematic review and meta-analysis to describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected patients, as reflected in the point prevalence of HIV DR at key points and fixed intervals after treatment initiation, using data from cohort studies and cross-sectional studies respectively. Results. Pooled prevalence of HIV DR from longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%–19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%–84.02%) after 72 months of HAART. The HIV DR prevalence from cross-sectional studies was measured in treatment intervals; during the 0–12-month HAART treatment interval, the pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%–16.14%), which increased to 22.92% at 61–72 months (95% CI, 9.45%–45.86%). Stratified analyses showed that patients receiving a didanosine-based regimen had higher HIV DR prevalence than those not taking didanosine (15.82% vs 4.97%). Patients infected through former plasma donation and those receiving AIDS treatment at village clinics had higher HIV DR prevalence than those infected through sexual transmission or treated at a county-level hospital. Conclusions. Our findings indicate higher prevalence of HIV DR for patients with longer cumulative HAART exposure, highlighting important subgroups for future HIV DR surveillance and control. PMID:25053721

  7. A novel tandem mass spectrometry method for first-line screening of mainly beta-thalassemia from dried blood spots.

    Science.gov (United States)

    Yu, Chaowen; Huang, Shuodan; Wang, Ming; Zhang, Juan; Liu, Hao; Yuan, Zhaojian; Wang, Xingbin; He, Xiaoyan; Wang, Jie; Zou, Lin

    2017-02-10

    Traditional methods for thalassemia screening are time-consuming and easily affected by cell hemolysis or hemoglobin degradation in stored blood samples. Tandem mass spectrometry (MS/MS) proved to be an effective technology for sickle cell disorders (SCD) screening. Here, we developed a novel MS/MS method for β-thalassemia screening from dried blood spots (DBS). Stable isotopic-labeled peptides were used as internal standards for quantification and calculation of the α:β-globin ratios. We used the α:β-globin ratio cutoffs to differentiate between normal individuals and patients with thalassemia. About 781 patients and 300 normal individuals were analyzed. The α:β-globin ratios showed significant difference between normal and β-thalassemia patients (Pthalassemia mutation. In the parallel study, all cases screened for suspected thalassemia from six hundred DBS samples by using this MS/MS method were successfully confirmed by genotyping. The intra-assay and inter-assay CVs of the ratios ranged from 2.4% to 3.9% and 4.7% to 7.1%, and there was no significant sample carryover or matrix effect for this MS/MS method. Combined with SCD screening, this MS/MS method could be used as a first-line screening assay for both structural and expression abnormalities of human hemoglobin. Traditional methods for thalassemia screening were depending on the structural integrity of tetramers and could be affected by hemolysis and degradation of whole blood samples, especially when stored. We used proteospecific peptides produced by the tryptic digestion of each globin to evaluate the production ratio between α- and β-globin chains, which turned out to be quite stable even when stored for more than two months. Though most of the peptides were specific to α-globin or β-globin, we only chose four most informative peptides and its stable isotopic-labeled peptides as internal standards for analysis, which could obtain a high accuracy. Currently, we are the first to address the

  8. The efficacy of two-week quadruple first-line therapy with bismuth, lansoprazole, amoxicillin, clarithromycin on Helicobacter pylori eradication: a prospective study.

    Science.gov (United States)

    Ergül, Bilal; Doğan, Zeynal; Sarikaya, Murat; Filik, Levent

    2013-12-01

    To document the efficacy and tolerability of 14-day bismuth-lansoprazole-amoxicillin-clarithromycin (BLAC) regimen for Helicobacter pylori (H. pylori) eradication as a first-line therapy. Patients were considered eligible for the study if they underwent upper gastrointestinal endoscopy, and H. pylori infection was diagnosed through histologic examination of antral and body biopsy samples. Primary end point of this study was to evaluate the eradication rate of 14-day BLAC regimen therapies. H. pylori eradication was assessed using the 13C urea breath test performed 6 weeks after the completion of treatment. All patients were asked to fill in a validated questionnaire to report therapy-related side effects. Each symptom was graded from absent or present. Ninety-seven (21 men and 76 women) were enrolled. All the patients completed the study. The H. pylori eradication rate was 90.7% (88 of 97 patients). Side effects were observed in reasonable percentages, and none of the patients left the study because of drug side effect. Bismuth-lansoprazole-amoxicillin-clarithromycin regimen as a 2-week course achieved an acceptable eradication rate with relatively mild side effects. © 2013 John Wiley & Sons Ltd.

  9. Medical Decision-Making Incapacity among Newly Diagnosed Older Patients with Hematological Malignancy Receiving First Line Chemotherapy: A Cross-Sectional Study of Patients and Physicians.

    Directory of Open Access Journals (Sweden)

    Koji Sugano

    Full Text Available Decision-making capacity to provide informed consent regarding treatment is essential among cancer patients. The purpose of this study was to identify the frequency of decision-making incapacity among newly diagnosed older patients with hematological malignancy receiving first-line chemotherapy, to examine factors associated with incapacity and assess physicians' perceptions of patients' decision-making incapacity.Consecutive patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Decision-making capacity was assessed using the Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory-Revised (SICIATRI-R. Cognitive impairment, depressive condition and other possible associated factors were also evaluated.Among 139 eligible patients registered for this study, 114 completed the survey. Of these, 28 (25%, 95% confidence interval [CI]: 17%-32% were judged as having some extent of decision-making incompetency according to SICIATRI-R. Higher levels of cognitive impairment and increasing age were significantly associated with decision-making incapacity. Physicians experienced difficulty performing competency assessment (Cohen's kappa -0.54.Decision-making incapacity was found to be a common and under-recognized problem in older patients with cancer. Age and assessment of cognitive impairment may provide the opportunity to find patients that are at a high risk of showing decision-making incapacity.

  10. A prognostic factor index for overall survival in patients receiving first-line chemotherapy for HER2-negative advanced breast cancer: an analysis of the ATHENA trial.

    Science.gov (United States)

    Llombart-Cussac, Antonio; Pivot, Xavier; Biganzoli, Laura; Cortes-Funes, Hernan; Pritchard, Kathleen I; Pierga, Jean-Yves; Smith, Ian; Thomssen, Christoph; Srock, Stefanie; Sampayo, Miguel; Cortes, Javier

    2014-10-01

    Evidence-based definitions of 'poor-prognosis' or 'aggressive' advanced breast cancer are lacking. We developed a prognostic factor index using data from 2203 patients treated with first-line chemotherapy plus bevacizumab for HER2-negative advanced breast cancer. The risk factors most closely associated with worse OS were: disease-free interval ≤24 months; liver metastases or ≥3 involved organ sites; prior anthracycline and/or taxane therapy; triple-negative breast cancer (TNBC); and performance status 2 or prior analgesic/corticosteroid treatment. Risk of death was increased threefold in patients with ≥3 versus ≤1 risk factors (hazard ratio 3.0 [95% CI 2.6-3.4; p < 0.001]; median 16.0 vs 38.8 months, respectively). This prognostic index may enable identification of patients with a poorer prognosis in whom more intensive systemic regimens may be appropriate. The index may also be considered in designing new trials, although it requires validation in other datasets before extrapolation to non-bevacizumab-containing therapy. ClinicalTrials.gov identifier: NCT00448591. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer.

    Science.gov (United States)

    Mellema, Wouter W; Masen-Poos, Lucie; Smit, Egbert F; Hendriks, Lizza E L; Aerts, Joachim G; Termeer, Arien; Goosens, Martijn J; Smit, Hans J M; van den Heuvel, Michel M; van der Wekken, Anthonie J; Herder, Gerarda J M; Krouwels, Frans H; Stigt, Jos A; van den Borne, Ben E E M; Haitjema, Tjeerd J; Staal-Van den Brekel, Agnes J; van Heemst, Robbert C; Pouw, Ellen; Dingemans, Anne-Marie C

    2015-11-01

    As suggested by in-vitro data, we hypothesize that subtypes of KRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinum-based chemotherapy, were retrieved from hospital databases. to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation. 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of KRAS mutation were G12C (46%), G12V (20%) and G12D (10%). Platinum was combined with pemetrexed (n=334), taxanes (n=68) or gemcitabine (n=62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; pchemotherapy had best ORR. Response to chemotherapy regimens was different in types of KRAS mutation. Especially patients with G12V had better response to taxane treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Randomize Trial of Cisplatin plus Gemcitabine with either Sorafenib or Placebo as First-line Therapy for Non-small Cell Lung Cancer

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    Yan WANG

    2011-03-01

    Full Text Available Background and objective Platinum-based chemotherapy doublets reached an efficacy plateau in nonsmall-cell lung cancer (NSCLC. This randomized controlled study prospectively assessed the efficacy and safety of cisplatin plus gemcitabine with either Sorafenib or placebo as first-line therapy for NSCLC. Methods Thirty patients, which were confirmed advanced NSCLC histologically or cytologically, were randomly assigned to receive up to six cycles of cisplatin plus gemcitabine with sorafenib or placebo. The maintenance of sorafenib or placebo after chemotherapy will continued in patients with response or stable disease until disease progression or unacceptable adverse events. Results Overall demographics were balanced between experimental group (sorafenib+chemotherapy and controlled group (chemotherapy only. Overall response (OS rate was 55.6% and 41.7% in experimental arm and controlled arm, respectively (P=0.905. Median progressivefree survival (PFS and median overall survial were similar (5 months vs 4 months, P=0.75; 18 months vs 18 months, P=0.68. Adverse events were tolerable, though the risk of hypertension and diarrhea was increase in experimental arm. Since patients with ECOG PS 0, stage IIIb, no liver metastasis and tyrasine kinasis inhibitor treatment after study had longer survive, these factors seemed to be predictive factors favor of survival in Cox regression analyses. Conclusion No additional benefit of response rate, PFS or OS were observed from adding targeted agent-sorafenib to regular cisplatin plus gemcitabine chemotherapy. Selecting aproper patients is needed in further study.

  13. [Randomize trial of cisplatin plus gemcitabine with either sorafenib or placebo as first-line therapy for non-small cell lung cancer].

    Science.gov (United States)

    Wang, Yan; Wang, Lin; Liu, Yutao; Yu, Shufei; Zhang, Xiangru; Shi, Yuankai; Sun, Yan

    2011-03-01

    Platinum-based chemotherapy doublets reached an efficacy plateau in nonsmall-cell lung cancer (NSCLC). This randomized controlled study prospectively assessed the efficacy and safety of cisplatin plus gemcitabine with either Sorafenib or placebo as first-line therapy for NSCLC. Thirty patients, which were confirmed advanced NSCLC histologically or cytologically, were randomly assigned to receive up to six cycles of cisplatin plus gemcitabine with sorafenib or placebo. The maintenance of sorafenib or placebo after chemotherapy will continued in patients with response or stable disease until disease progression or unacceptable adverse events. Overall demographics were balanced between experimental group (sorafenib+chemotherapy) and controlled group (chemotherapy only). Overall response (OS) rate was 55.6% and 41.7% in experimental arm and controlled arm, respectively (P=0.905). Median progressive-free survival (PFS) and median overall survival were similar (5 months vs 4 months, P=0.75; 18 months vs 18 months, P=0.68). Adverse events were tolerable, though the risk of hypertension and diarrhea was increase in experimental arm. Since patients with ECOG PS 0, stage IIIb, no liver metastasis and tyrasine kinasis inhibitor treatment after study had longer survive, these factors seemed to be predictive factors favor of survival in Cox regression analyses. No additional benefit of response rate, PFS or OS were observed from adding targeted agent-sorafenib to regular cisplatin plus gemcitabine chemotherapy. Selecting aproper patients is needed in further study.

  14. Clomiphene citrate, metformin or a combination of both as the first line ovulation induction drug for Asian Indian women with polycystic ovarian syndrome: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Sujata Kar

    2015-01-01

    Full Text Available Aim: To compare clomiphene citrate (CC, metformin or the combination of CC and metformin as the first line ovulation induction drug in Asian Indian women with polycystic ovary syndrome (PCOS. Methods: One hundred and five newly diagnosed, treatment naive PCOS women were recruited. They were randomized into any of the three groups: Group I (CC 50-150 mg/day, Group II (metformin 1700 mg/day, and Group III (CC + metformin in similar dosage to Groups I and II. Patients underwent follicular monitoring and advice on timed intercourse. The study period was 6 months, or till pregnant, or till CC resistant. Primary outcome studied was live birth rate (LBR. Secondary outcomes were ovulation rate, pregnancy rate, and early pregnancy loss rate. Results: There was no significant difference among the groups in baseline characteristics and biochemical parameters. LBR was 41.6%, 37.5%, and 28.1%, respectively in Groups III, II, and I. Group III (CC + metformin had the highest ovulation (83.3%, pregnancy (50%, and LBRs (41.6%. Group II (metformin was as good as Group I (CC in all the outcomes. CC + metformin (Group III had statistically significantly higher ovulation rate as compared to CC alone (Group I (P = 0.03; odds ratio: 95% confidence interval: 3.888 [1.08-13.997]. Conclusion: Thus, our study shows that metformin was as good as CC in terms of "LBR" and the combination of CC and metformin gave the highest ovulation and LBR.

  15. THROMBOCYTOSIS AS PROGNOSTIC FACTOR FOR SURVIVAL IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER TREATED WITH FIRST- LINE CHEMOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

    Full Text Available Objective: The aim of this study was to evaluate elevated platelet count as a prognostic factor for survival in patients with advanced (stage IIIB/ IV non- small cell lung cancer (NSCLC receiving first- line chemotherapy. Methods: From 2005 to 2009 three hundreds forty seven consecutive patients with stage IIIB or IV NSCLC, treated in Department of Medical Oncology, UMHAT "Dr Georgi Stranski" entered the study. The therapeutic regimens included intravenous administration of platinum- based doublets. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment thrombocytosis as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: Elevated platelet counts were found in 78 patients. The overall survival for patients without elevated platelet counts was 9,6 months versus 6,9 months for these with thrombocytosis. In multivariate analysis as independent poor prognostic factors were identified: stage, performance status and elevated platelet counts. Conclusions: These results indicated that platelet counts as well as some clinical pathologic characteristics could be useful prognostic factors in patients with unresectable NSCLC.

  16. First-line chemotherapy with S-1 alone or S-1 plus cisplatin for elderly patients with advanced gastric cancer: a multicenter propensity score matched study.

    Science.gov (United States)

    Makiyama, Akitaka; Kunieda, Kenji; Noguchi, Masaaki; Kajiwara, Takeshi; Tamura, Takao; Takeda, Koji; Sugiyama, Junko; Minashi, Keiko; Moriwaki, Toshikazu; Sugimoto, Naotoshi; Nagase, Michitaka; Negoro, Yuji; Tsuda, Takashi; Shimodaira, Hideki; Okano, Naohiro; Tsuji, Akihito; Sakai, Daisuke; Yanagihara, Kazuhiro; Ueda, Shinya; Tamura, Shingo; Otsu, Satoshi; Honda, Takuya; Matsushita, Yuzo; Okuno, Tatsuya; Kashiwada, Tomomi; Nozaki, Akira; Ebi, Masahide; Okuda, Hiroyuki; Shimokawa, Mototsugu; Hironaka, Shuichi; Hyodo, Ichinosuke; Baba, Eishi; Boku, Narikazu; Muro, Kei; Esaki, Taito

    2018-01-20

    Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability. In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors. PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients' characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p strategy and explore applicability of the geriatric assessment for these patients.

  17. Phase I and pharmacodynamic study of vorinostat combined with capecitabine and cisplatin as first-line chemotherapy in advanced gastric cancer.

    Science.gov (United States)

    Yoo, Changhoon; Ryu, Min-Hee; Na, Young-Soon; Ryoo, Baek-Yeol; Lee, Chae-Won; Maeng, Jeheon; Kim, Se-Yeon; Koo, Dong Hoe; Park, Inkeun; Kang, Yoon-Koo

    2014-04-01

    A phase I trial of first-line vorinostat, an orally bio-available histone deacetylase inhibitor, in combination with capecitabine plus cisplatin (XP) was performed to assess recommend phase II trial dose in patients with advanced gastric cancer. Five dose levels of three-weekly vorinostat-XP were tested; vorinostat was dosed at 300-400 mg once daily on Days 1-14, capecitabine at 800-1,000 mg/m(2) twice daily on Days 1-14, and cisplatin at 60-80 mg/m(2) on Day 1. To assess the pharmacodynamics of vorinostat, histone H3 acetylation was assessed in peripheral blood mononuclear cells before the study treatment and at Day 8 of cycle 1. In total, 30 patients with unresectable or metastatic gastric adenocarcinoma were included. Dose-limiting toxicities were thrombocytopenia, fatigue, stomatitis, and anorexia. The following doses were recommended for phase II trial: 400 mg of vorinostat once daily, 1,000 mg/m(2) of capecitabine twice daily, and 60 mg/m(2) of cisplatin. The most common grade 3-4 toxicities were neutropenia (47 %), anorexia (20 %), thrombocytopenia (17 %), and fatigue (13 %). In overall, response rate was 56 % (95 % confidence interval [CI]: 32-81). With a median follow-up of 14.1 months, the median progression-free survival and overall survival were 7.1 months (95 % CI: 3.8-10.3) and 18.0 months (95 % CI: 4.8-31.1), respectively. The change in H3 acetylation after treatment with vorinostat correlated significantly with the vorinostat dose (300 vs. 400 mg/day) and the baseline level of H3 acetylation before treatment. Three-weekly vorinostat-XP regimen is feasible and recommended for further development in advanced gastric cancer.

  18. Axenic isolation of viable Giardia muris trophozoites.

    Science.gov (United States)

    Tillotson, K D; Buret, A; Olson, M E

    1991-06-01

    Large numbers of viable Giardia muris trophozoites were isolated from the duodenum of experimentally infected mice 6 days after inoculation with 1,000 G. muris cysts. A series of shaking, incubation, and washing steps in the presence of the broad-spectrum antibiotic piperacillin readily provided 4.9 +/- 1.5 x 10(5) G. muris trophozoites per mouse, free of detectable contaminant organisms. Anaerobic and microaerophilic culturing and scanning electron microscopy demonstrated axenic status and high purity of the isolates. The viability of trophozoites was 98 +/- 2%. Application of this technique should permit novel immunological and epidemiological analyses of G. muris infection and biochemical investigations of this protozoan parasite.

  19. Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa.

    Science.gov (United States)

    Penrose, Kerri J; Wallis, Carole L; Brumme, Chanson J; Hamanishi, Kristen A; Gordon, Kelley C; Viana, Raquel V; Harrigan, P Richard; Mellors, John W; Parikh, Urvi M

    2017-02-01

    A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa. Plasma samples were obtained from individuals with >10,000 copies of HIV RNA/ml and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation. Susceptibility to NVP, EFV, and DPV in TZM-bl cells was determined for recombinant HIV-1 LAI containing bulk-amplified, plasma-derived, full-length reverse transcriptase sequences. Fold change (FC) values were calculated compared with a composite 50% inhibitory concentration (IC 50 ) from 12 recombinant subtype C HIV-1 LAI plasma-derived viruses from treatment-naive individuals in South Africa. A total of 25/100 (25%) samples showed >500-FCs to DPV compared to treatment-naive samples with IC 50 s exceeding the maximum DPV concentration tested (132 ng/ml). A total of 66/100 (66%) samples displayed 3- to 306-FCs, with a median IC 50 of 17.6 ng/ml. Only 9/100 (9%) samples were susceptible to DPV (FC 500-fold resistance to DPV compared to samples with a ≤500-fold resistance. A total of 91% of samples with NNRTI-resistant HIV-1 from individuals on failing first-line ART in South Africa exhibited ≥3-fold cross-resistance to DPV. This level of resistance exceeds expected plasma concentrations, but very high genital tract DPV concentrations from DPV ring use could block viral replication. It is critically important to assess the frequency of transmitted and selected DPV resistance in individuals using the DPV ring. Copyright © 2017 American Society for Microbiology.

  20. Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia.

    Science.gov (United States)

    Le Bris, Yannick; Struski, Stéphanie; Guièze, Romain; Rouvellat, Caroline; Prade, Naïs; Troussard, Xavier; Tournilhac, Olivier; Béné, Marie C; Delabesse, Eric; Ysebaert, Loïc

    2017-12-01

    Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of remarkable heterogeneity as demonstrated by cytogenetics and molecular analyses. Complex karyotype (CK), TP53 deletions and/or mutations (TP53 disruption), IGVH mutational status, and, more recently, recurrent somatic mutations have been identified as prognostic markers in CLL. On a cohort of 110 patients with CLL treated with first-line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P < .0001), ATM deletion (25 vs 6%, P = .02), and NOTCH mutation (3 vs 17%, P = .04). Among treated patients, 39 relapsed during the follow-up period. These patients were characterized before treatment by a higher incidence of trisomy 12 (38 vs 11%, P < .001) and TP53 disruption (31 vs 4%, P = .0002). A significantly shorter 5-year overall survival was found for treated patients with CK (72.4 vs 85.8%; P = .007), unmutated IGHV (70 vs 100%; P = .04), or TP53 disruption (55.7 vs 82.7%; P < .0001). Three risk groups were defined based on the status of TP53 disruption or unmutated IGVH, which differed significantly in terms of 5-year overall survival. Moreover, the presence of CK impacted pejoratively 5-year overall survival and progression-free survival in all these 3 groups. Conventional karyotyping therefore appears to be of value, CK being an additional factor, undetectable in classical FISH, in patients with CLL at the stage when therapy becomes required. Copyright © 2016 John Wiley & Sons, Ltd.

  1. [First line management without IVF of infertility related to endometriosis: Result of medical therapy? Results of ovarian superovulation? Results of intrauterine insemination? CNGOF-HAS Endometriosis Guidelines].

    Science.gov (United States)

    Boujenah, J; Santulli, P; Mathieu-d'Argent, E; Decanter, C; Chauffour, C; Poncelet, P

    2018-03-01

    Using the structured methodology of French guidelines (HAS-CNGOF), the aim of this chapter was to formulate good practice points (GPP), in relation to optimal non-ART management of endometriosis related to infertility, based on the best available evidence in the literature. This guideline was produced by a group of experts in the field including a thorough systematic search of the literature (from January 1980 to March 2017). Were included only women with endometriosis related to infertility. For each recommendation, a grade (A-D, where A is the highest quality) was assigned based on the strength of the supporting evidence. Management of endometriosis related to infertility should be multidisciplinary and take account into the pain, the global evaluation of infertile couple and the different phenotypes of endometriotic lesions (good practice point). Hormonal treatment for suppression of ovarian function should not prescribe to improve fertility (grade A). After laproscopy for endometriosis related to infertility, the Endometriosis Fertility Index should be used to counsel patients regarding duration of conventional treatments before undergoing ART (grade C). After laparoscopy surgery for infertile women with AFS/ASRM stage I/II endometriosis or superficial peritoneal endometriosis, controlled ovarian stimulation with or without intrauterine insemination could be used to enhance non-ART pregnancy rate (grade C). Gonadotrophins should be the first line therapy for the stimulation (grade B). The number of cycles before referring ART should not exceed up to 6 cycles (good practice point). No recommendation can be performed for non-ART management of deep infiltrating endometriosis or endometrioma, as suitable evidence is lacking. Non-ART management is a possible option for the management of endometriosis related to infertility. Endometriosis Fertilty Index could be a useful tool for subsequent postoperative fertility management. Controlled ovarian stimulation can be

  2. Clinical decision-making and health-related quality of life during first-line and maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC): findings from a real-world setting.

    Science.gov (United States)

    Sztankay, Monika; Giesinger, Johannes Maria; Zabernigg, August; Krempler, Elisabeth; Pall, Georg; Hilbe, Wolfgang; Burghuber, Otto; Hochmair, Maximilian; Rumpold, Gerhard; Doering, Stephan; Holzner, Bernhard

    2017-08-23

    Maintenance therapy (MT) with pemetrexed has been shown to improve overall and progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC), without impairing patients' health-related quality of life (HRQOL) substantially. Comprehensive data on HRQOL under real-life conditions are necessary to enable informed decision-making. This study aims to (1) assess HRQOL during first-line chemotherapy and subsequent MT and (2) record patients' and physicians' reasons leading to clinical decisions on MT. Patients treated for NSCLC at three Austrian medical centres were included. HRQOL was assessed at every chemotherapy cycle using the EORTC QLQ-C30/+LC13 questionnaire. Semi-structured interviews were conducted before MT initiation and at the time of discontinuation to evaluate patients' and physicians' reasons for treatment decisions. Longitudinal QOL analysis was based on linear mixed models. Sixty-one (73%) out of 84 patients were considered for MT. Thirty-six patients (43%) received MT and 29 (35%) discontinued therapy. Decisions on MT initiation (in 20 cases by the physician vs 4 by the patient) and discontinuation (19 vs 10) were mainly voiced by the physician. Treatment toxicity of first-line chemotherapy was the main reason for rejection of MT in patients with stable disease and was more often indicated by patients than clinicians. HRQOL data were collected from 83 patients at 422 assessment time points and indicated significantly lower symptom severity during MT compared with first-line therapy for nausea and vomiting (p = 0.006), sleep disturbances (p loss (p = 0.043), constipation (p = 0.017) and chest pain (p = 0.022), and a deterioration in emotional functioning (p = 0.023) and cognitive functioning (p = 0.044) during MT. Our results indicate that HRQOL and symptom burden improve between first-line treatment to MT in some respects, although some late toxicity persists. Discrepancies between patients' and physicians

  3. Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice.

    Science.gov (United States)

    Santoro, Maria Mercedes; Di Carlo, Domenico; Armenia, Daniele; Zaccarelli, Mauro; Pinnetti, Carmela; Colafigli, Manuela; Prati, Francesca; Boschi, Andrea; Antoni, Anna Maria Degli; Lagi, Filippo; Sighinolfi, Laura; Gervasoni, Cristina; Andreoni, Massimo; Antinori, Andrea; Mussini, Cristina; Perno, Carlo Federico; Borghi, Vanni; Sterrantino, Gaetana

    2017-09-22

    Virological success (VS) and immunological reconstitution (IR) of antiretroviral-naive HIV-1-infected patients with pre-therapy viral load (VL) >500,000 copies/ml was assessed after 12 months of treatment according to initial drug-class regimens. An observational multicentre retrospective study was performed. VS was defined as the first VL 500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.

  4. Network Meta-analysis for Clinical Practice Guidelines: A Case Study on First-Line Medical Therapies for Primary Open-Angle Glaucoma

    Science.gov (United States)

    Rouse, Benjamin; Cipriani, Andrea; Shi, Qiyuan; Coleman, Anne L.; Dickersin, Kay; Li, Tianjing

    2016-01-01

    Background Network meta-analysis compares multiple treatment options for the same condition and may be useful for developing clinical practice guidelines. Purpose To compare treatment recommendations for first-line medical therapy for primary open angle-glaucoma (POAG) from major updates of American Academy of Ophthalmology (AAO) guidelines with the evidence available at the time, using network meta-analysis. Data Sources MEDLINE, Embase, and the Cochrane Library were searched on 11 March 2014 for randomized, controlled trials (RCTs) of glaucoma monotherapies compared with placebo, vehicle, or no treatment or other monotherapies. The AAO Web site was searched in August 2014 to identify AAO POAG guidelines. Study Selection Eligible RCTs were selected by 2 independent reviewers, and guidelines were selected by 1 person. Data Extraction One person abstracted recommendations from guidelines and a second person verified. Two people independently abstracted data from included RCTs. Data Synthesis Guidelines were grouped together on the basis of literature search dates, and RCTs that existed at 1991, 1995, 1999, 2004, and 2009 were analyzed. The outcome of interest was intraocular pressure (IOP) at 3 months. Only the latest guideline made a specific recommendation: prostaglandins. Network meta-analyses showed that all treatments were superior to placebo in decreasing IOP at 3 months. The mean reductions (95% credible intervals [CrIs]) for the highest-ranking class compared with placebo were as follows: 1991: β-blockers, 4.01 (CrI, 0.48 to 7.43); 1995: α2-adrenergic agonists, 5.64 (CrI, 1.73 to 9.50); 1999: prostaglandins, 5.43 (CrI, 3.38 to 7.38); 2004: prostaglandins, 4.75 (CrI, 3.11 to 6.44); 2009: prostaglandins, 4.58 (CrI, 2.94 to 6.24). Limitation When comparisons are informed by a small number of studies, the treatment effects and rankings may not be stable. Conclusion For timely recommendations when multiple treatment options are available, guidelines developers

  5. Eligibility of Metastatic Pancreatic Cancer Patients for First-Line Palliative Intent nab-Paclitaxel Plus Gemcitabine Versus FOLFIRINOX.

    Science.gov (United States)

    Peixoto, Renata D; Ho, Maria; Renouf, Daniel J; Lim, Howard J; Gill, Sharlene; Ruan, Jenny Y; Cheung, Winson Y

    2017-10-01

    The PRODIGE and MPACT trials showed superiority of FOLFIRINOX and nab-paclitaxel plus gemcitabine (NG) over gemcitabine alone, respectively. However, both had strict inclusion criteria. We sought to determine the characteristics of patients with metastatic pancreatic cancer (MPC) which inform the appropriateness of first-line chemotherapy FOLFIRINOX and NG in routine practice. Patients with MPC who initiated palliative chemotherapy with gemcitabine from 2000 to 2011 at the British Columbia Cancer Agency were identified. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. Eligibility criteria for each regimen were in accordance with the respective pivotal phase III trials. A total of 473 patients were included: 25% of the patients were eligible for FOLFIRINOX versus 45% for NG. Main reasons for FOLFIRINOX ineligibility were Eastern Cooperative Oncology Group (ECOG) performance status (PS)≥2 (56.5%), age older than 75 years (19.0%), and bilirubin>1.5× upper limit of normal (18.6%), whereas those for NG ineligibility were bilirubin > upper limit of normal (24.5%), ECOG PS≥3 (14.6%), and cardiac dysfunction (13.8%). Univariate analyses revealed that FOLFIRINOX and NG-eligible patients had longer median overall survival than their respective ineligible group (8.6 vs. 4.7 mo, Paccounting for ECOG PS in the multivariate model, however, eligibility for either FOLFIRINOX or NG no longer predicted for better overall survival. The majority of patients with MPC are not candidates to either NG or FOLFIRINOX due to restrictive eligibility requirements. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

  6. Semi-quantitative analysis of salivary gland scintigraphy in Sjögren's syndrome diagnosis: a first-line tool.

    Science.gov (United States)

    Angusti, Tiziana; Pilati, Emanuela; Parente, Antonella; Carignola, Renato; Manfredi, Matteo; Cauda, Simona; Pizzigati, Elena; Dubreuil, Julien; Giammarile, Francesco; Podio, Valerio; Skanjeti, Andrea

    2017-09-01

    The aim of this study was the assessment of semi-quantified salivary gland dynamic scintigraphy (SGdS) parameters independently and in an integrated way in order to predict primary Sjögren's syndrome (pSS). Forty-six consecutive patients (41 females; age 61 ± 11 years) with sicca syndrome were studied by SGdS after injection of 200 MBq of pertechnetate. In sixteen patients, pSS was diagnosed, according to American-European Consensus Group criteria (AECGc). Semi-quantitative parameters (uptake (UP) and excretion fraction (EF)) were obtained for each gland. ROC curves were used to determine the best cut-off value. The area under the curve (AUC) was used to estimate the accuracy of each semi-quantitative analysis. To assess the correlation between scintigraphic results and disease severity, semi-quantitative parameters were plotted versus Sjögren's syndrome disease activity index (ESSDAI). A nomogram was built to perform an integrated evaluation of all the scintigraphic semi-quantitative data. Both UP and EF of salivary glands were significantly lower in pSS patients compared to those in non-pSS (p quantitative parameters and ESSDAI. The proposed nomogram accuracy was 87%. SGdS is an accurate and reproducible tool for the diagnosis of pSS. ESSDAI was not shown to be correlated with SGdS data. SGdS should be the first-line imaging technique in patients with suspected pSS.

  7. Quadruple-first line drug resistance in Mycobacterium tuberculosis in Vietnam: What can we learn from genes?

    Science.gov (United States)

    Nguyen, Huy Quang; Nguyen, Nhung Viet; Contamin, Lucie; Tran, Thanh Hoa Thi; Vu, Thuong Thi; Nguyen, Hung Van; Nguyen, Ngoc Lan Thi; Nguyen, Son Thai; Dang, Anh Duc; Bañuls, Anne-Laure; Nguyen, Van Anh Thi

    2017-06-01

    In Vietnam, a country with high tuberculosis (137/100.000 population) and multidrug-resistant (MDR)-TB burdens (7.8/100.000 population), little is known about the molecular signatures of drug resistance in general and more particularly of second line drug (SLD) resistance. This study is specifically focused on Mycobacterium tuberculosis isolates resistant to four first-line drugs (FLDs) that make TB much more difficult to treat. The aim is to determine the proportion of SLD resistance in these quadruple drug resistant isolates and the genetic determinants linked to drug resistance to better understand the genetic processes leading to quadruple and extremely drug resistance (XDR). 91 quadruple (rifampicin, isoniazid, ethambutol and streptomycin) FLD resistant and 55 susceptible isolates were included. Spoligotyping and 24-locus MIRU-VNTR techniques were performed and 9 genes and promoters linked to FLD and SLD resistance were sequenced. SLD susceptibility testing was carried out on a subsample of isolates. High proportion of quadruple-FLD resistant isolates was resistant to fluoroquinolones (27%) and second-line injectable drugs (30.2%) by drug susceptibility testing. The sequencing revealed high mutation diversity with prevailing mutations at positions katG315, inhA-15, rpoB531, embB306, rrs1401, rpsL43 and gyrA94. The sensitivity and specificity were high for most drug resistances (>86%), but the sensitivity was lower for injectable drug resistances (resistance. Nevertheless, particular mutation patterns linked to high-level resistance and low fitness costs seem to be favored. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Economic implications of using bendamustine, alemtuzumab, or chlorambucil as a first-line therapy for chronic lymphocytic leukemia in the US: a cost-effectiveness analysis

    Directory of Open Access Journals (Sweden)

    Kongnakorn T

    2014-04-01

    Full Text Available Thitima Kongnakorn,1 James A Sterchele,2 Christopher G Salvador,3 Denis Getsios,4 Mkaya Mwamburi51Evidera, Bangkok, Thailand; 2formerly of Teva Branded Pharmaceutical Products R&D, Inc, Frazer, PA, 3Oncology Market Research, Teva Branded Pharmaceutical Products R&D, Inc, Frazer, PA, 4Evidera, Lexington, MA, 5Tufts University School of Medicine, Public Health and Community Medicine, Boston, MA, USABackground: The objective of this analysis was to evaluate the cost-effectiveness of using bendamustine versus alemtuzumab or bendamustine versus chlorambucil as a first-line therapy in patients with Binet stage B or C chronic lymphocytic leukemia (CLL in the US.Methods: A discrete event simulation of the disease course of CLL was developed to evaluate the economic implications of single-agent treatment with bendamustine, alemtuzumab, or chlorambucil, which are indicated for a treatment-naïve patient population with Binet stage B or C CLL. Data from clinical trials were used to create a simulated patient population, risk equations for progression-free survival and survival post disease progression, response rates, and rates of adverse events. Costs from a US health care payer perspective in 2012 US dollars, survival (life years, and quality-adjusted life years (QALYs were estimated over a patient's lifetime; all were discounted at 3% per year.Results: Compared with alemtuzumab, bendamustine was considered to be a dominant treatment providing greater benefit (6.10 versus 5.37 life years and 4.02 versus 3.45 QALYs at lower cost ($78,776 versus $121,441. Compared with chlorambucil, bendamusti