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Sample records for trial comparing paclitaxel

  1. A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer

    International Nuclear Information System (INIS)

    Geara, Fady B; Shamseddine, Ali; Khalil, Ali; Abboud, Mirna; Charafeddine, Maya; Seoud, Muhieddine

    2010-01-01

    This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma. Between May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m 2 Cisplatin (group I; 16 patients) or 50 mg/m 2 paclitaxel (group II; 15 patients) concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy) for group I and 66 Gy (range: 40-98 Gy) for group II. Median follow-up time was 46 months. Patient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44%) of group I and 8 patients (53%) of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively. This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix

  2. An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer.

    Science.gov (United States)

    Park, In Hae; Sohn, Joo Hyuk; Kim, Sung Bae; Lee, Keun Seok; Chung, Joo Seop; Lee, Soo Hyeon; Kim, Tae You; Jung, Kyung Hae; Cho, Eun Kyung; Kim, Yang Soo; Song, Hong Suk; Seo, Jae Hong; Ryoo, Hun Mo; Lee, Sun Ah; Yoon, So Young; Kim, Chul Soo; Kim, Yong Tai; Kim, Si Young; Jin, Mi Ryung; Ro, Jungsil

    2017-07-01

    Genexol-PM is a Cremophor EL-free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m 2 or Genexol 175 mg/m 2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m 2 (95.0%), and that of Genexol was 168.3±10.6 mg/m 2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p non-inferiority =0.021, p superiority =0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p cancer.

  3. Comparison of everolimus- and paclitaxel-eluting stents in patients with acute and stable coronary syndromes: pooled results from the SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) Trials.

    Science.gov (United States)

    Planer, David; Smits, Pieter C; Kereiakes, Dean J; Kedhi, Elvin; Fahy, Martin; Xu, Ke; Serruys, Patrick W; Stone, Gregg W

    2011-10-01

    This study sought to compare the clinical outcomes of everolimus-eluting stents (EES) versus paclitaxel-eluting stents (PES) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). Although randomized trials have shown superiority of EES to PES, the safety and efficacy of EES in ACS is unknown. We performed a patient-level pooled analysis from the prospective, randomized SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) II, III, IV, and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) trials in which 2,381 patients with ACS and 4,404 patients with stable CAD were randomized to EES or to PES. Kaplan-Meier estimates of death, myocardial infarction (MI), ischemia-driven target lesion revascularization, and stent thrombosis were assessed at 2 years and stratified by clinical presentation (ACS vs. stable CAD). At 2 years, patients with ACS compared with stable CAD had higher rates of death (3.2% vs. 2.4%, hazard ratio [HR]: 1.37 [95% confidence interval (CI): 1.02 to 1.85], p = 0.04) and MI (4.9% vs. 3.4%, HR: 1.45 [95% CI: 1.14 to 1.85], p = 0.02). In patients with ACS, EES versus PES reduced the rate of death or MI (6.6% vs. 9.3%, HR: 0.70 [95% CI: 0.52 to 0.94], p = 0.02), stent thrombosis (0.7% vs. 2.9%, HR: 0.25 [95% CI: 0.12 to 0.52], p = 0.0002), and ischemia-driven target lesion revascularization (4.7% vs. 6.2%, HR: 0.69 [95% CI: 0.48 to 0.99], p = 0.04). In patients with stable CAD, EES reduced the rate of death or MI (4.5% vs. 7.1%, HR: 0.62 [95% CI: 0.48 to 0.80], p = 0.0002), stent thrombosis (0.7% vs. 1.8%, HR: 0.34 [95% CI: 0.19 to 0.62], p = 0.0002), and ischemia-driven target lesion revascularization (3.9% vs. 6.9%, HR: 0.55 [95% CI: 0.42 to 0.73], p SPIRIT II]; NCT00180310; SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the

  4. Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial.

    Science.gov (United States)

    Awada, Ahmad; Colomer, Ramon; Inoue, Kenichi; Bondarenko, Igor; Badwe, Rajendra A; Demetriou, Georgia; Lee, Soo-Chin; Mehta, Ajay O; Kim, Sung-Bae; Bachelot, Thomas; Goswami, Chanchal; Deo, Suryanarayan; Bose, Ron; Wong, Alvin; Xu, Feng; Yao, Bin; Bryce, Richard; Carey, Lisa A

    2016-12-01

    Efficacious ERBB2 (formerly HER2 or HER2/neu)-directed treatments, in addition to trastuzumab and lapatinib, are needed. To determine whether neratinib, an irreversible pan-ERBB tyrosine kinase inhibitor, plus paclitaxel improves progression-free survival compared with trastuzumab plus paclitaxel in the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer. In the randomized, controlled, open-label NEfERT-T trial conducted from August 2009 to December 2014 at 188 centers in 34 countries in Europe, Asia, Africa, and North America, 479 women with previously untreated recurrent and/or metastatic ERBB2-positive breast cancer were randomized to 1 of 2 treatment arms (neratinib-paclitaxel [n = 242] or trastuzumab-paclitaxel [n = 237]). Women with asymptomatic central nervous system metastases were eligible, and randomization was stratified by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Women received neratinib (240 mg/d orally) or trastuzumab (4 mg/kg then 2 mg/kg weekly), each combined with paclitaxel (80 mg/m2 on days 1, 8, and 15 every 28 days). Primary prophylaxis for diarrhea was not mandatory. The primary outcome was progression-free survival. Secondary end points were response rate, clinical benefit rate, duration of response, frequency, and time to symptomatic and/or progressive central nervous system lesions, and safety. The intent-to-treat population comprised 479 women 18 years or older (neratinib-paclitaxel, n = 242; trastuzumab-paclitaxel, n = 237) randomized and stratified in their respective treatment arms by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Median progression-free survival was 12.9 months (95% CI, 11.1-14.9) with neratinib-paclitaxel and 12.9 months (95% CI, 11.1-14.8) with trastuzumab-paclitaxel (hazard ratio [HR], 1.02; 95% CI, 0.81-1.27; P =.89). With neratinib-paclitaxel, the incidence of central nervous system recurrences was

  5. Nanoparticle albumin-bound paclitaxel: a novel Cremphor-EL-free formulation of paclitaxel.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2007-08-01

    Standard formulation paclitaxel requires the use of solvents, such as Cremphor-EL, which contribute to some of the toxicities commonly associated with paclitaxel-based therapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel solvent-free formulation of paclitaxel. The formulation is prepared by high-pressure homogenization of paclitaxel in the presence of serum albumin into a nanoparticle colloidal suspension. The human albumin-stabilized paclitaxel particles have an average size of 130 nm. Nab-paclitaxel has several practical advantages over Cremphor-EL-paclitaxel, including a shorter infusion time (30 min) and no need for premedications for hypersensitivity reactions. The nab-paclitaxel formulation eliminates the impact of Cremphor-EL on paclitaxel pharmacokinetics and utilizes the endogenous albumin transport mechanisms to concentrate nab-paclitaxel within the tumor. A recent Phase III trial compared nab- and Cremphor-EL-paclitaxel in patients with metastatic breast cancer. Patients treated with nab-paclitaxel experienced a higher response, longer time to tumor progression and, in patients receiving second-line or greater therapy, a longer median survival. Patients treated with nab-paclitaxel had a significantly lower rate of severe neutropenia and a higher rate of sensory neuropathy. The preclinical and clinical data indicate that the nab-paclitaxel formulation has significant advantages over Cremphor-EL-paclitaxel.

  6. Comparative effectiveness of early-line nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer: a US community-based real-world analysis

    Directory of Open Access Journals (Sweden)

    Mahtani RL

    2018-02-01

    Full Text Available Reshma L Mahtani,1 Monika Parisi,2 Stefan Glück,3 Quanhong Ni,2 Siyeon Park,4 Corey Pelletier,2 Claudio Faria,2 Fadi Braiteh5,6 1Division of Hematology/Oncology, University of Miami, Miami, FL, 2Health Economics and Outcomes Research, Celgene Corporation, Summit, NJ, 3Global Medical Affairs, Celgene Corporation, Summit, NJ, 4School of Pharmacy, The Ohio State University, Columbus, OH, 5Department of Hematology/Oncology, University of Nevada School of Medicine, Las Vegas, NV, 6Department of Hematology/Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA Background: Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA.Methods: We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab-paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014. The clinical efficacy objectives were time to treatment discontinuation (TTD and time to next treatment (TTNT. Subgroup analyses were performed in patients with 2 types of metastatic breast cancer as follows: 1 hormone receptor-positive and human epidermal growth factor receptor 2 negative, and 2 triple-negative disease. Results: This analysis included 925 patients. Patients receiving nab-paclitaxel vs. paclitaxel had significantly longer TTD (median 4.2 vs. 2.8 months, P<0.0001 and TTNT (median 6.0 vs. 4.2 months, P<0.0001; similar outcomes were observed for patients with hormone receptor-positive/human epidermal growth factor receptor 2 negative disease. Compared with paclitaxel, nab-paclitaxel was associated with significantly longer TTD in patients with triple

  7. A randomized, controlled, multicenter trial to evaluate the safety and efficacy of Zotarolimus- vs. Paclitaxel-eluting stents in de novo occlusive lesions in coronary arteries

    DEFF Research Database (Denmark)

    Chevalier, Bernard; Dimario, Carlo; Neumann, Franz-Josef

    2013-01-01

    The ZOMAXX I trial tested the noninferiority of a zotarolimus-eluting coronary stent (ZoMaxx(™) ) when compared with a paclitaxel-eluting coronary stent (Taxus(™) Express(2™) ) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. Angiographic analysis at the pr...

  8. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.

    Science.gov (United States)

    Wilke, Hansjochen; Muro, Kei; Van Cutsem, Eric; Oh, Sang-Cheul; Bodoky, György; Shimada, Yasuhiro; Hironaka, Shuichi; Sugimoto, Naotoshi; Lipatov, Oleg; Kim, Tae-You; Cunningham, David; Rougier, Philippe; Komatsu, Yoshito; Ajani, Jaffer; Emig, Michael; Carlesi, Roberto; Ferry, David; Chandrawansa, Kumari; Schwartz, Jonathan D; Ohtsu, Atsushi

    2014-10-01

    VEGFR-2 has a role in gastric cancer pathogenesis and progression. We assessed whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel. This randomised, placebo-controlled, double-blind, phase 3 trial was done at 170 centres in 27 countries in North and South America, Europe, Asia, and Australia. Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy (platinum plus fluoropyrimidine with or without an anthracycline) were randomly assigned with a centralised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15, plus paclitaxel 80 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle. A permuted block randomisation, stratified by geographic region, time to progression on first-line therapy, and disease measurability, was used. The primary endpoint was overall survival. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one treatment with study drug. This trial is registered with ClinicalTrials.gov, number NCT01170663, and has been completed; patients who are still receiving treatment are in the extension phase. Between Dec 23, 2010, and Sept 23, 2012, 665 patients were randomly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel. Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group (median 9·6 months [95% CI 8·5-10·8] vs 7·4 months [95% CI 6·3-8·4], hazard ratio 0·807 [95% CI 0·678-0·962]; p=0·017). Grade 3 or higher adverse events that occurred in more than 5% of patients in the ramucirumab plus paclitaxel group versus placebo

  9. A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524)

    Energy Technology Data Exchange (ETDEWEB)

    Michaelson, M. Dror, E-mail: dmichaelson1@partners.org [Massachusetts General Hospital Cancer Center, Boston, Massachusetts (United States); Hu, Chen [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Pham, Huong T. [Virginia Mason CCOP, Seattle, Washington (United States); Dahl, Douglas M.; Lee-Wu, Chin [Massachusetts General Hospital Cancer Center, Boston, Massachusetts (United States); Swanson, Gregory P. [University of Texas at San Antonio, San Antonio, Texas (United States); Vuky, Jacqueline [Virginia Mason CCOP, Seattle, Washington (United States); Lee, R. Jeffrey [Intermountain Medical Center, Murray, Utah (United States); Souhami, Luis [McGill University, Montréal, Quebec (Canada); Chang, Brian [Parkview Cancer Center, Parkview Hospital, Fort Wayne, Indiana (United States); George, Asha [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, California (United States); Shipley, William [Massachusetts General Hospital Cancer Center, Boston, Massachusetts (United States)

    2017-04-01

    Purpose: Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab. Methods and Materials: Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completion rate, and survival. Results: A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2. Conclusions: In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.

  10. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer.

    Science.gov (United States)

    Bishop, J F; Dewar, J; Toner, G C; Smith, J; Tattersall, M H; Olver, I N; Ackland, S; Kennedy, I; Goldstein, D; Gurney, H; Walpole, E; Levi, J; Stephenson, J; Canetta, R

    1999-08-01

    To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P = .07). Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.

  11. Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT trial).

    Science.gov (United States)

    Ruddy, Kathryn J; Guo, Hao; Barry, William; Dang, Chau T; Yardley, Denise A; Moy, Beverly; Marcom, P Kelly; Albain, Kathy S; Rugo, Hope S; Ellis, Matthew J; Shapira, Iuliana; Wolff, Antonio C; Carey, Lisa A; Overmoyer, Beth A; Hudis, Clifford; Krop, Ian E; Burstein, Harold J; Winer, Eric P; Partridge, Ann H; Tolaney, Sara M

    2015-06-01

    Chemotherapy-related amenorrhea (CRA) is associated with infertility and menopausal symptoms. Learning how frequently paclitaxel and trastuzumab cause amenorrhea is important. Most other adjuvant breast cancer therapies induce CRA in approximately 50 % of all premenopausal recipients [1]. 410 patients enrolled on the APT Trial, a single-arm phase 2 adjuvant study of 12 weeks of paclitaxel and trastuzumab followed by nine months of trastuzumab monotherapy. Eligible patients had ≤3 cm node-negative HER2 + breast cancers. Premenopausal enrollees were asked to complete menstrual surveys every 3-12 months for 72 months. Women who responded to at least one survey at least 15 months after chemotherapy initiation (and who did not undergo hysterectomy and/or bilateral oophorectomy or receive ovarian suppressing medications prior to 15 months) were included in this analysis. A participant was defined as having amenorrhea in follow-up if her self-reported last menstrual period at last follow-up was greater than 12 months prior to the survey. Among the 64 women in the evaluable population (median age at study entry 44 years, range 27-52 years), the median time between chemotherapy initiation and last menstrual survey was 51 months (range 16-79). 18 of 64 women (28 %, 95 % CI 18-41 %) were amenorrheic at that time point. Amenorrhea rates among premenopausal women treated with adjuvant paclitaxel and trastuzumab for early stage breast cancer appear lower than those seen historically with standard alkylator-based breast cancer regimens. Future studies are needed to understand the impact of this regimen on related issues of fertility and menopausal symptoms.

  12. Phase I trial of nanoparticle albumin-bound paclitaxel in combination with gemcitabine in patients with thoracic malignancies.

    Science.gov (United States)

    Stinchcombe, Thomas E; Socinski, Mark A; Lee, Carrie B; Hayes, D Neil; Moore, Dominic T; Goldberg, Richard M; Dees, E Claire

    2008-05-01

    Nab-paclitaxel has a different toxicity profile than solvent-based paclitaxel including a lower rate of severe neutropenia. This trial was designed to determine the maximum tolerated dose and dose limiting toxicities (DLT) of nab-paclitaxel in combination with gemcitabine. Patients were required to have a performance status of 0 to 1, < or = three prior cytotoxic chemotherapy regimens, and preserved renal, hepatic, and bone marrow function. Patients received gemcitabine 1000 mg/m on days 1, 8 in all cohorts, and nab-paclitaxel at doses of 260, 300, 340 mg/m every 21 days depending on the treatment cohort (1 cycle = 21 days). DLT were assessed after the first cycle, and doses were escalated in cohorts of 3 to 6 patients. Eighteen patients were consented and 15 patients are evaluable [median age 62 years (range, 35-75); median number of prior treatments 3 (range, 1-4); tumor types: non-small cell lung cancer (NSCLC) (n = 8), small cell lung cancer (SCLC) (n = 6), and esophageal cancer (n = 1)]. At a nab-paclitaxel dose of 300 mg/m, 1 of 6 pts experienced a DLT (omission of day 8 gemcitabine due to absolute neutrophil count < 500), and at an nab-paclitaxel dose of 340 mg/m 2 of 3 patients experienced a DLT (1 pt grade 3 rash and pruritus; 1 pt grade 3 fatigue and anorexia). Responses were observed in NSCLC and SCLC. The maximum tolerated dose of nab-paclitaxel is 300 mg/m in combination with gemcitabine 1000 mg/m on days 1, 8 every 21 days. This combination demonstrated activity in previously treated NSCLC and SCLC patients.

  13. Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer

    Science.gov (United States)

    Tabchy, Adel; Valero, Vicente; Vidaurre, Tatiana; Lluch, Ana; Gomez, Henry; Martin, Miguel; Qi, Yuan; Barajas-Figueroa, Luis Javier; Souchon, Eduardo; Coutant, Charles; Doimi, Franco D; Ibrahim, Nuhad K; Gong, Yun; Hortobagyi, Gabriel N; Hess, Kenneth R; Symmans, W Fraser; Pusztai, Lajos

    2010-01-01

    Purpose We examined in a prospective, randomized, international clinical trial the performance of a previously defined 30-gene predictor (DLDA-30) of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil, doxorubicin, cyclophosphamide (T/FAC) chemotherapy, and assessed if DLDA-30 also predicts increased sensitivity to FAC-only chemotherapy. We compared the pCR rates after T/FAC versus FAC×6 preoperative chemotherapy. We also performed an exploratory analysis to identify novel candidate genes that differentially predict response in the two treatment arms. Experimental Design 273 patients were randomly assigned to receive either weekly paclitaxel × 12 followed by FAC × 4 (T/FAC, n=138), or FAC × 6 (n=135) neoadjuvant chemotherapy. All patients underwent a pretreatment FNA biopsy of the tumor for gene expression profiling and treatment response prediction. Results The pCR rates were 19% and 9% in the T/FAC and FAC arms, respectively (pcancers. PMID:20829329

  14. 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-paclitaxel

  15. Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

    Directory of Open Access Journals (Sweden)

    Maria Graziella Catalano

    2016-01-01

    Full Text Available Anaplastic thyroid cancer (ATC has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly and valproic acid (1,000 mg/day; the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11.

  16. Nab-paclitaxel for the treatment of breast cancer: efficacy, safety, and approval

    Directory of Open Access Journals (Sweden)

    Iwase H

    2011-07-01

    Full Text Available Yutaka Yamamoto1, Ichiro Kawano2, Hirotaka Iwase11Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Surgery, Asahino General Hospital, Kumamoto, JapanAbstract: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel is a novel formulation of paclitaxel that does not require solvents such as polyoxyethylated castor oil and ethanol. Use of these solvents has been associated with toxic response, including hypersensitivity reactions and prolonged sensory neuropathy, as well as a negative impact in relation to the therapeutic index of paclitaxel. nab-paclitaxel displays greater antitumor activity and less toxicity than solvent-base paclitaxel. In a phase I trial of single nab-paclitaxel, the maximum tolerated dose was 300 mg/m2 with the dose limiting toxicities being sensory neuropathy, stomatitis, and superficial keratopathy. In the metastatic setting, a pivotal comparative randomized phase III study demonstrated that nab-paclitaxel (at 260 mg/m2 over 30 minutes infusion without premedication every 3 weeks mediated a superior objective response rate and prolonged time to progression compared with solvent-based paclitaxel (at 175 mg/m2 over a 3-hour injection with standard premedication. The nab-paclitaxel-treated group showed a higher incidence of sensory neuropathy than the solvent-based paclitaxel group. However, these adverse side effects rapidly resolved after interruption of treatment and dose reduction. Weekly administration of nab-paclitaxel was also more active and displayed less toxicity compared with 100 mg/m2 docetaxel given triweekly. Nab-paclitaxel has already been approved in 42 countries for the treatment of metastatic breast cancer previously treated with anthracycline, based on confirmation of the efficacy and manageable toxicity in the metastatic setting. This review summarizes the most relevant knowledge on nab-paclitaxel for treating breast cancer

  17. Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114).

    Science.gov (United States)

    Schwartz, Gary K; Winter, Kathryn; Minsky, Bruce D; Crane, Christopher; Thomson, P John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

    2009-04-20

    The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.

  18. Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Fushida S

    2015-04-01

    Full Text Available Sachio Fushida,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Hideaki Nezuka,4 Toshiya Takeda,5 Tomoya Tsukada,1 Daisuke Fujimoto,3 Shigekazu Ohyama,6 Takashi Fujimura,7 Tetsuo Ohta1 On behalf of the Digestive Disease Support Organization (DDSO 1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, 2Department of Surgery, Toyama Prefectural Central Hospital, Toyama, 3First Department of Surgery, Fukui University Hospital, Fukui, 4Department of Surgery, Yatsuo General Hospital, Toyama, 5Department of Surgery, Ishikawa Matto Central Hospital, Hakusan, 6Department of Surgery, Kanazawa Medical Center, Kanazawa, 7Toyama City Hospital, Toyama, Japan Abstract: The standard regimen of second-line chemotherapy for patients with unresectable gastric cancer has not been established. However, weekly paclitaxel (wPTX has become the preferable second-line chemotherapy in Japan. Histone deacetylase (HDAC inhibitors have been shown to have antiproliferative activity through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC inhibitor, valproic acid (VPA, also inhibits tumor growth by inducing apoptosis, and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve survival in gastric cancer patients. A multicenter randomized Phase II study was conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66 patients participated in this study. The primary end point of the study was overall survival, and secondary end points were progression-free survival, response rate, and assessment of peripheral neuropathy. Keywords: valproic acid, paclitaxel, second-line therapy, advanced gastric cancer 

  19. A phase I clinical trial of bavituximab and paclitaxel in patients with HER2 negative metastatic breast cancer

    International Nuclear Information System (INIS)

    Chalasani, Pavani; Marron, Marilyn; Roe, Denise; Clarke, Kathryn; Iannone, Maria; Livingston, Robert B; Shan, Joseph S; Stopeck, Alison T

    2015-01-01

    Bavituximab is a chimeric monoclonal antibody that targets phosphatidylserine (PS). PS is externalized on cells in the tumor microenvironment when exposed to hypoxia and/or other physiological stressors. On attaching to PS, bavituximab is thought to promote antitumor immunity through its effects on PS receptors in monocytes, and myeloid-derived suppressor cells, as well as trigger antitumor effects by inducing an antibody-dependent cellular cytotoxicity on tumor-associated endothelial cells. We conducted a phase I clinical trial of bavituximab in combination with paclitaxel in patients with HER2-negative metastatic breast cancer. Patients were treated with weekly paclitaxel (80 mg/m 2 for 3/4 weeks) and weekly bavituximab (3 mg/kg for 4/4 weeks). Correlative studies included the measurement of circulating microparticles, endothelial cells, and apoptotic tumor cells by flow cytometry. Fourteen patients with metastatic breast cancer were enrolled; all were evaluable for toxicity and 13 were evaluable for response. Treatment resulted in an overall response rate (RR) of 85% with a median progression-free survival (PFS) of 7.3 months. Bone pain, fatigue, headache, and neutropenia were the most common adverse effects. Infusion-related reactions were the most common adverse event related to bavituximab therapy. Correlative studies showed an increase in the PS-expressing apoptotic circulating tumor cells in response to bavituximab, but not with paclitaxel. No changes in the number of circulating endothelial cells or apoptotic endothelial cells were observed with therapy. Platelet and monocyte-derived microparticles decreased after initiation of bavituximab. Bavituximab in combination with paclitaxel is well tolerated for treatment of patients with metastatic breast cancer with promising results observed in terms of clinical RRs and PFS. The toxicity profile of bavituximab is notable for manageable infusion-related reactions with no evidence for increased thrombogenicity

  20. Differentiated analysis of an everolimus-eluting stent and a paclitaxel-eluting stent among higher risk subgroups for restenosis: results from the SPIRIT II trial.

    Science.gov (United States)

    Khattab, Ahmed A; Richardt, Gert; Verin, Vitali; Kelbaek, Henning; Macaya, Carlos; Berland, Jacques; Miquel-Hebert, Karine; Dorange, Cécile; Serruys, Patrick W

    2008-03-01

    Restenosis is higher among certain subpopulations when subjected to percutaneous coronary interventions even when using drug-eluting stents. The randomised SPIRIT II trial demonstrated the superiority of the XIENCE V Everolimus Eluting Coronary Stent System over the TAXUS Paclitaxel-Eluting Stent System in terms of in-stent late loss at six months among 300 patients treated for de novo native coronary artery lesions. In this post-hoc analysis of SPIRIT II we focused on six-month angiographic outcomes of diabetic patients (n=69), left anterior descending arteries (n=149), long lesions >20 mm (n=43), small vessels B2 and C lesions (n=233). In-stent late loss was consistently less among all subgroups when treated by everolimus-eluting stents compared to paclitaxel-eluting stents: diabetics 0.15+/-0.26 mm versus 0.39+/-0.34 mm, p=0.006; LAD 0.12+/-0.23 mm versus 0.44+/-0.37 mm, pB2/C lesions 0.12+/-0.31 mm versus 0.36+/-0.36 mm, pSPIRIT II trial population.

  1. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...... of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity....... In order to overcome these various types of heterogeneity and to compare like with like, the treatment comparison should be stratified a posteriori by question (i.e., type of castration or type of anti-androgen studied) and by study. In this way, one may draw valid conclusions. Of course, those trials...

  2. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Ghoreishi Zohreh

    2012-08-01

    Full Text Available Abstract Background Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. Methods This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN. Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". Results Twenty one patients (70% of the group taking omega-3 fatty acid supplement (n = 30 did not develop PN while it was 40.7%( 11 patients in the placebo group(n = 27. A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88, p = 0.029. There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (−2.06 -0.02, p = 0.054. Conclusions Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients’ quality of life. Trial registration This trial was registered at ClinicalTrials.gov (NCT01049295

  3. nab-Paclitaxel/carboplatin in elderly patients with advanced squamous non-small cell lung cancer: a retrospective analysis of a Phase III trial

    Directory of Open Access Journals (Sweden)

    Gridelli C

    2018-05-01

    Full Text Available Cesare Gridelli,1 Tianlei Chen,2 Amy Ko,2 Mary E O’Brien,3 Teng Jin Ong,4 Mark A Socinski,5 Pieter E Postmus6 1Division of Medical Oncology, S. G. Moscati Hospital, Avellino, Italy; 2Biostatistics, Celgene Corporation, Summit, NJ, USA; 3Medical Oncology, Royal Marsden Hospital, London, UK; 4Medical Affairs, Celgene Corporation, Summit, NJ, USA; 5Lung Cancer & Esophageal Cancer, Florida Hospital Cancer Institute, Orlando, FL, USA; 6Pulmonary Diseases, Clatterbridge Cancer Center, Liverpool, UK Background: Limited data on elderly patients with squamous advanced non-small cell lung cancer (NSCLC preclude optimal treatment. Here, we report the outcomes of a retrospective analysis of a subset of patients ≥70 years with squamous histology from the Phase III trial that evaluated nab-paclitaxel/carboplatin vs paclitaxel/carboplatin. Patients and methods: Patients with stage IIIB/IV NSCLC received (1:1 nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 or paclitaxel 200 mg/m2 on day 1, both with carboplatin area under the curve 6 mg×min/mL on day 1 every 3 weeks. The primary endpoint was independently assessed overall response rate as per the Response Evaluation Criteria in Solid Tumors v1.0. Secondary endpoints included progression-free survival, overall survival, and safety. Results: Sixty-five patients ≥70 years with squamous histology were included (nab-paclitaxel/carboplatin, n=35; paclitaxel/carboplatin, n=30. nab-Paclitaxel/carboplatin vs paclitaxel/carboplatin, respectively, resulted in an overall response rate of 46% vs 20% (response rate ratio, 2.29, P=0.029 and a median overall survival of 16.9 vs 8.6 months (hazard ratio, 0.50, P=0.018. No difference was observed in median progression-free survival (5.7 months for both. Incidences of grade 3/4 neutropenia (50% vs 63%, leukopenia (29% vs 37%, fatigue (3% vs 13%, and peripheral neuropathy (3% vs 13% were lower, but those of thrombocytopenia (21% vs 10% and anemia (21% vs 7% were higher with

  4. Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

    Science.gov (United States)

    Schwartz, Gary K.; Winter, Kathryn; Minsky, Bruce D.; Crane, Christopher; Thomson, P. John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

    2009-01-01

    Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin–containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin–containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. PMID:19273696

  5. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer

    DEFF Research Database (Denmark)

    de Wit, Ronald; Skoneczna, Iwona; Daugaard, Gedske

    2012-01-01

    To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC)....

  6. Comparative study of adsorptive role of carbonaceous materials in removal of UV-active impurities of paclitaxel extracts

    Directory of Open Access Journals (Sweden)

    Jaber Nasiri

    2015-12-01

    Full Text Available Graphite oxide (GO and reduced graphene oxide (rGO nanosheets were synthesized with a low-cost manufacturing method. The morphology and structures of the synthesized samples were studied using X-ray diffraction (XRD, atomic force microscopy (AFM, Fourier-transform infrared (FTIR and Raman spectroscopy. The efficiencies of GO and rGO as novel candidate adsorbents in the pre-purification of paclitaxel were compared and contrasted with those of commercial graphite (Gt, graphene (G and multi-wall carbon nanotube (MWCNT. According to UV–vis and HPLC analyses, rGO was evaluated as the best absorbent for the removal of impurities in pre-purification of paclitaxel from plant cell cultures. In contrast, the GO had the poorest proficiency for paclitaxel pre-purification in comparison with the other carbonaceous adsorbents. This is attributed to the existence of many localized defects in the π-structure of GO that is related to weakness of π–π stacking interactions between crude extract impurities and GO.

  7. Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

    Science.gov (United States)

    Socinski, M A; Clark, J A; Halle, J; Steagall, A; Kaluzny, B; Rosenman, J G

    1997-08-01

    Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

  8. Comparison between the STENTYS self-apposing bare metal and paclitaxel-eluting coronary stents for the treatment of saphenous vein grafts (ADEPT trial)

    NARCIS (Netherlands)

    A.J.J. IJsselmuiden (Alexander); C. Simsek (Cihan); Van Driel, A.G. (A. G.); Bouchez, D. (D.); G. Amoroso (Giovanni); P. Vermeersch (Paul); Karjalainen, P.P. (P. P.)

    2018-01-01

    textabstractAims To describe the safety and performance of STENTYS self-expandable bare metal stents (BMS) versus paclitaxel-eluting stents (PES) in saphenous vein grafts (SVGs). Methods and Results A randomised controlled trial was performed in four hospitals in three European countries between

  9. Paclitaxel Injection

    Science.gov (United States)

    (pak'' li tax' el)Paclitaxel injection must be given in a hospital or medical facility under the supervision of a doctor who is experienced in giving chemotherapy medications for cancer.Paclitaxel injection may cause a large decrease in the number of white blood cells (a type of blood cell ...

  10. Phase II trial of paclitaxel and cisplatin in patients with extensive stage small cell lung cancer: Cancer and Leukemia Group B Trial 9430.

    Science.gov (United States)

    Stinchcombe, Thomas E; Mauer, Ann M; Hodgson, Lydia D; Herndon, James E; Lynch, Thomas J; Green, Mark R; Vokes, Everett E

    2008-11-01

    Cancer and Leukemia Group B trial 9430 was a randomized phase II trial which investigated the safety and activity of four novel doublets in untreated extensive stage small cell lung cancer. The results of the paclitaxel and cisplatin arm have not been reported. Patients received paclitaxel 230 mg/m followed by cisplatin 75 mg/m on day 1 every 21 days. All patients received granulocyte colony stimulating factor 5 microg/kg/d beginning on day 3 of each cycle. The patient characteristics of the 34 patients assigned to this treatment arm were: median age 61.5 years (range 41-82), male (76%), performance status 0 (41%), 1 (32%), and 2 (26%). An objective response was observed in 23 patients (68%; 95% confidence interval (CI): 49-83%); 2 complete responses (6%) and 21 partial responses (62%). Median progression-free survival time was 5.6 months (95% CI: 4.8-7.1 month), and median overall survival time was 7.7 months (95% CI: 7.2-12.6 months). The 1-year survival rate observed was 29% (95% CI: 15-45%). Grade 3/4 neutropenia and thrombocytopenia was observed in 5 (15%) and 4 (12%) patients, respectively. Two patients developed febrile neutropenia including one patient who died of neutropenic sepsis. Grade 3/4 nonhematologic observed were: sensory neuropathy in eight patients (24%); and hyperglycemia, malaise and nausea were all observed in four patients (12%). Cancer and Leukemia Group B will not pursue further investigation of paclitaxel and cisplatin due to the modest activity and the toxicity observed on this trial.

  11. Phase II Radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme

    International Nuclear Information System (INIS)

    Langer, Corey J.; Ruffer, James; Rhodes, Harker; Paulus, Rebecca; Murray, Kevin; Movsas, Benjamin; Curran, Walter

    2001-01-01

    Purpose: Fractionated external beam radiotherapy (EBRT) ± carmustine (BCNU) is the standard of care for patients with glioblastoma multiforme (GBM), but survival results remain poor. Preclinical studies indicate synergy between RT and paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have demonstrated a maximum tolerated dose for TAX of 225 mg/m 2 /3 h/week x 6, during EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation Therapy Oncology Group (RTOG) therefore mounted a Phase II study to determine the feasibility and efficacy of conventional EBRT and concurrent weekly TAX at its MTD. Patients and Methods: Sixty-two patients with histologic diagnosis of GBM were enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II trial of EBRT and TAX 225 mg/m 2 /3 h (1-3 h before EBRT), administered the first treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/fraction), 5 days per week. A smaller treatment field, to include gross disease plus a margin only, was used after 46 Gy. Results: Sixty-one patients (98%) were evaluable. Median age was 55 years (range, 28-78). Seventy-four percent were ≥50 years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10 (17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total resection was performed in only 16%. There was no Grade 3 or 4 neutropenia or thrombocytopenia. Hypersensitivity reactions precluding further use of TAX occurred in 4 patients. There were 2 instances of late neurotoxicity (4% Grade 3 or 4). Ninety-one percent of patients received treatment per protocol. Seventy-seven percent completed prescribed treatment (6 weeks). Of 35 patients with measurable disease, CR/PR was observed in 23%, MR in 17%, and SD in 43%. Seventeen percent demonstrated progression at first follow-up. Median potential follow-up time is 20 months. Median survival is 9.7 months, with median survivals for RPA classes III, IV, V, and VI of 16.3, 10

  12. Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

    Science.gov (United States)

    Romond, Edward H.; Jeong, Jong-Hyeon; Rastogi, Priya; Swain, Sandra M.; Geyer, Charles E.; Ewer, Michael S.; Rathi, Vikas; Fehrenbacher, Louis; Brufsky, Adam; Azar, Catherine A.; Flynn, Patrick J.; Zapas, John L.; Polikoff, Jonathan; Gross, Howard M.; Biggs, David D.; Atkins, James N.; Tan-Chiu, Elizabeth; Zheng, Ping; Yothers, Greg; Mamounas, Eleftherios P.; Wolmark, Norman

    2012-01-01

    Purpose Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2–positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab. PMID:22987084

  13. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...

  14. Nab-paclitaxel, docetaxel, or solvent-based paclitaxel in metastatic breast cancer: a cost-utility analysis from a Chinese health care perspective

    Directory of Open Access Journals (Sweden)

    Dranitsaris G

    2015-05-01

    Full Text Available George Dranitsaris,1 Bo Yu,2 Jennifer King,3 Satyin Kaura,3 Adams Zhang3 1Augmentium Pharma Consulting Inc., Toronto, ON, Canada; 2Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; 3Celgene Corporation, Summit, NJ, USA Background: Paclitaxel and docetaxel are commonly used for metastatic breast cancer in the People’s Republic of China. To improve the safety and efficacy of paclitaxel, an albumin-bound formulation (nab is now available in the People's Republic of China (Abraxane®. To provide health economic data for the key stakeholders, a cost-utility analysis comparing nab-paclitaxel to docetaxel, both as alternatives to paclitaxel, was conducted. Methods: A meta-analysis of clinical outcomes Phase III trials comparing nab-paclitaxel (260 mg/m2 every [q] 3 weeks or branded docetaxel (100 mg/m2 q 3 weeks, to solvent-based branded paclitaxel (175 mg/m2 q 3 weeks was undertaken to provide safety and clinical data. Resource use data for the delivery of anticancer therapy and for the treatment of grade 3/4 toxicity was collected from a time and motion study conducted in three Chinese cancer centers and from a survey of clinicians. Using the Time Trade-Off technique, health utility estimates were derived from interviewing 28 breast cancer patients from one cancer center in the People's Republic of China. All costs were reported in 2014 US dollars. Results: Nab-paclitaxel had the most favorable safety profile, characterized with the lowest incidence of grade 3/4 neutropenia, febrile neutropenia, anemia, and stomatitis. When the median number of cycles delivered from the clinical trials was applied, nab-paclitaxel had a cost per course of $19,752 compared with $8,940 and $13,741 for paclitaxel and docetaxel, respectively. As an alternative to paclitaxel, the cost per quality-adjusted life-year (QALY gained with nab-paclitaxel suggested better value than with docetaxel ($57,900 vs $130,600. Conclusion: Nab-paclitaxel

  15. A study of concurrent radiochemotherapy with paclitaxel in glioblastoma multiforme

    International Nuclear Information System (INIS)

    Julka, P.K.; Awasthy, B.S.; Rath, G.K.; Agarwal, S.; Varna, T.; Mahapatra, A.K.; Singh, R.

    2000-01-01

    Despite advances in neurosurgery and radiotherapy, the prognosis of patients with glioblastoma multiforme remains poor. Reports in the literature about the radiosensitizing properties of paclitaxel stimulated the authors to conduct a study using paclitaxel concurrently with radiation in a group of 18 patients who had residual disease postoperatively. Paclitaxel was delivered weekly as an intravenous infusion in a dose of 60 mg/m 2 along with radiation to the primary lesion. A total of 108 cycles of paclitaxel was given. All the patients tolerated the treatment well. The main side effects were haematological, and neuropathy which was self-limiting. The overall 1-year survival rate was 70%, with 12 patients alive at 13 months. The median survival has not yet been reached although it is more than 13 months. Thus, paclitaxel can be safely delivered concomitantly with radiation in patients with glioblastoma multiforme. Larger, randomized trials are required to establish the comparative efficacy of paclitaxel as a radiosensitizer in glioblastoma multiforme. Copyright (1999) Blackwell Science Pty Ltd

  16. Is a reduction in radiation lung volume and dose necessary with paclitaxel chemotherapy for node-positive breast cancer?

    Science.gov (United States)

    Taghian, Alphonse G; Assaad, Sherif I; Niemierko, Andrzej; Floyd, Scott R; Powell, Simon N

    2005-06-01

    To evaluate and quantify the effect of irradiated lung volume, radiation dose, and paclitaxel chemotherapy on the development of radiation pneumonitis (RP) in breast cancer patients with positive lymph nodes. We previously reported the incidence of RP among 41 patients with breast cancer treated with radiotherapy (RT) and adjuvant paclitaxel-containing chemotherapy. We recorded the central lung distance, a measure of the extent of lung included in the RT volume, in these patients. We used this measure and the historical and observed rates of RP in our series to model the lung tolerance to RT in patients receiving chemotherapy (CHT) both with and without paclitaxel. To evaluate the risk factors for the development of RP, we performed a case-control study comparing paclitaxel-treated patients who developed RP with those who did not, and a second case-control study comparing patients receiving paclitaxel in addition to standard CHT/RT (n = 41) and controls receiving standard CHT/RT alone (n = 192). The actuarial rate of RP in the paclitaxel-treated group was 15.4% compared with 0.9% among breast cancer patients treated with RT and non-paclitaxel-containing CHT. Our mathematical model found that the effective lung tolerance for patients treated with paclitaxel was reduced by approximately 24%. No statistically significant difference was found with regard to the dose delivered to specific radiation fields, dose per fraction, central lung distance, or percentage of lung irradiated in the case-control study of paclitaxel-treated patients who developed RP compared with those who did not. In the comparison of 41 patients receiving RT and CHT with paclitaxel and 192 matched controls receiving RT and CHT without paclitaxel, the only significant differences identified were the more frequent use of a supraclavicular radiation field and a decrease in the RT lung dose among the paclitaxel-treated patients. This finding indicates that the major factor associated with development

  17. Weekly dose-dense paclitaxel and carboplatin in recurrent ovarian carcinoma: A phase II trial

    International Nuclear Information System (INIS)

    Shawky, H.; Tawfik, H.; Hewidy, M.

    2014-01-01

    Purpose: The aim of this study was to investigate efficacy and toxicity of the dose-dense weekly paclitaxel (T) and carboplatin (C) in the management of platinum-resistant/sensitive recurrent epithelial ovarian cancer (EOC) previously treated with 3 weekly paclitaxel/carboplatin. Methods: Thirty two patients with recurrent EOC who had received 3 weekly TC before were enrolled. Nine patients relapsed within 6 months (platinum-resistant), 13 patients relapsed after 12 months (platinum-sensitive) and in 10 patients recurrence occurred between 6 and 12 months (intermediate platinum-sensitive). Weekly (T) at a dose of 80 mg/m2, followed by weekly (C) AUC 2 on day 1, 8, and 15 of a 28-day cycle for 6 planned cycles were administrated. End-points were overall response rate (ORR), progression free survival (PFS), overall survival (OS) and toxicity. Results: The ORR was 62.5%. For the platinum-resistant, intermediate platinum-sensitive and platinum-sensitive patients the ORR was 44.4% (4/9), 60% (6/10) and 76.9% (10/13), respectively, and 1 (11.1%), 2 (20%) and 5 (38.46%) patients, respectively had CR. PFS was 9.1 months (6.13, 9.1 and 12.17 months, for the 3 groups, respectively) (P < 0.001). OS was 14 months (9.17, 15.2, and 19.23 months, for the 3 groups, respectively) (P < 0.001). Treatment-related adverse events were manageable with only 1 patient (3.1%) suffering from grade 4 neutropenia. Grade 3 hematological and non-hematological toxicities were neutropenia in 8 (25%), and peripheral neuropathy in 4 (12.5%) patients, respectively. Conclusion: Weekly TC is active and well-tolerated in platinum-resistant and platinum-sensitive patients with recurrent EOC previously treated with TC given every 3 weeks

  18. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: Intergroup study EORTC 30983

    NARCIS (Netherlands)

    R. de Wit (Ronald); I. Skoneczna (I.); G. Daugaard (Gedske); M. de Santis (Maria); A. Garin (A.); N. Aass (N.); J.A. Witjes (Alfred); P. Albers (Peter); J.D. White (Jeffrey); J.R. Germa-Lluch; S. Marreaud (Sandrine); L.A.J. Collette (Lau)

    2012-01-01

    textabstractPurpose: To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC). Patients and Methods: Patients were

  19. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial

    Directory of Open Access Journals (Sweden)

    Tabernero J

    2017-02-01

    Full Text Available Josep Tabernero,1 Volker Kunzmann,2 Werner Scheithauer,3 Michele Reni,4 Jack Shiansong Li,5 Stefano Ferrara,6 Kamel Djazouli7 1Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain; 2Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany; 3Medizinische Universität Wien, Wien, Austria; 4San Raffaele Scientific Institute, Milan, Italy; 5Celgene Corporation, Summit, NJ, USA; 6Celgene Corporation, Boudry, Switzerland; 7Celgene Corporation, Paris, France Purpose: The global Phase III MPACT trial demonstrated superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone as first-line treatment for metastatic pancreatic cancer. Region was a randomization stratification factor in the MPACT trial. This subgroup analysis of MPACT examined efficacy and safety of patients treated in Western Europe.Patients and methods: Patients received nab-paclitaxel plus gemcitabine or gemcitabine alone as first-line treatment for metastatic pancreatic cancer as previously described. A total of 76 patients were included in this analysis (n=38 for each arm.Results: Differences between the overall Western European cohort and the intention-to-treat population included lower percentages of male patients (46% and 58%, respectively and patients with biliary stents (8% and 17%, and higher percentages of patients with Karnofsky performance status of 90–100 (78% and 60% and primary tumors in the body of the pancreas (48% and 31%. The median overall survival was 10.7 months with nab-paclitaxel plus gemcitabine vs 6.9 months with gemcitabine alone (hazard ratio [HR]: 0.82 [95% confidence interval (CI: 0.48–1.40]; P=0.471. Median progression-free survival was 5.3 vs 3.7 months, respectively (HR: 0.70 [95% CI: 0.37–1.33]; P=0.277. The independently assessed overall response rate was 18% vs 5% (response rate ratio, 3.50 [95% CI: 0.78–15.78]; P=0.076. The most common grade ≥3 adverse events with nab-paclitaxel

  20. Subgroup analysis of East Asians in RAINBOW: A phase 3 trial of ramucirumab plus paclitaxel for advanced gastric cancer.

    Science.gov (United States)

    Muro, Kei; Oh, Sang Cheul; Shimada, Yasuhiro; Lee, Keun-Wook; Yen, Chia-Jui; Chao, Yee; Cho, Jae Yong; Cheng, Rebecca; Carlesi, Roberto; Chandrawansa, Kumari; Orlando, Mauro; Ohtsu, Atsushi

    2016-03-01

    East Asia has higher gastric cancer incidence and mortality rates than other regions. We present a subgroup analysis of East Asians in the positive study RAINBOW. Patients with advanced gastric or gastroesophageal junction adenocarcinoma previously treated with platinum and fluoropyrimidine received ramucirumab 8 mg/kg or placebo on days 1 and 15 plus paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Of 665 intention-to-treat patients, 223 were East Asian. Median overall survival was 12.1 months for ramucirumab plus paclitaxel and 10.5 months for placebo plus paclitaxel (hazard ratio: 0.986, 95% confidence interval: 0.727-1.337, P = 0.929). Median progression-free survival was 5.5 months for ramucirumab plus paclitaxel and 2.8 months for placebo plus paclitaxel (hazard ratio: 0.628, 95% confidence interval: 0.473-0.834, P = 0.001). Objective response rates were 34% for ramucirumab plus paclitaxel and 20% for placebo plus paclitaxel. Grade ≥ 3 neutropenia (60% vs 28%) and leukopenia (34% vs 13%) were higher for ramucirumab plus paclitaxel. The rate of febrile neutropenia was low (4% vs 4%). Special interest adverse events included any grade bleeding/hemorrhage (55% vs 25%), proteinuria (27% vs 7%), and hypertension (22% vs 2%). Ramucirumab plus paclitaxel significantly improves progression-free survival and response rate, with prolonged median overall survival and an acceptable safety profile in East Asians with advanced gastric cancer. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  1. Incidence and risk of peripheral neuropathy with nab-paclitaxel in patients with cancer: a meta-analysis.

    Science.gov (United States)

    Peng, L; Bu, Z; Ye, X; Zhou, Y; Zhao, Q

    2017-09-01

    Nab-paclitaxel, a Cremophor EL-free formulation of paclitaxel, is used to treat various malignancies. Peripheral neuropathy is one of its major toxicities, although the overall incidence remains unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy in cancer patients treated with nab-paclitaxel and to compare the relative risk (RR) with conventional taxanes. The electronic databases were searched for relevant clinical trials. Eligible studies included phase II and III prospective clinical trials of cancer patients treated with nab-paclitaxel with toxicity profile on peripheral neuropathy. Statistical analyses were done to calculate summary incidences, RRs and 95% confidence intervals (CI), using fixed-effects or random-effects models based on the heterogeneity of the included studies. Nineteen trials were selected for the meta-analysis, yielding a total of 2878 cancer patients. The overall incidences of peripheral neuropathy (all-grade) was 51.0% (95% CI: 45.1-57.6%), and that of high-grade peripheral neuropathy was 12.4% (9.8-15.7%). The RRs of peripheral neuropathy of nab-paclitaxel compared to taxanes were not increased for all-grade and high-grade peripheral neuropathy. Nab-paclitaxel is associated with an increased risk of developing peripheral neuropathy. Future clinical studies are still needed to investigate the risk reduction and possible use of nab-paclitaxel. © 2015 John Wiley & Sons Ltd.

  2. Paclitaxel: a pharmacoeconomic review of its use in non-small cell lung cancer.

    Science.gov (United States)

    Plosker, G L; Hurst, M

    2001-01-01

    A number of first-line chemotherapy options for patients with advanced non-small cell lung cancer (NSCLC) are advocated in treatment guidelines and/or by various clinical investigators. Platinum-based chemotherapy has clearly demonstrated efficacy in patients with advanced NSCLC and is generally recommended as first-line therapy, although there is increasing interest in the use of non-platinum chemotherapy regimens. Among the platinum-based combinations currently used in clinical practice are regimens such as cisplatin or carboplatin combined with paclitaxel, vinorelbine, gemcitabine, docetaxel or irinotecan. The particular combinations employed may vary between institutions and geographical regions. Several pharmacoeconomic analyses have been conducted on paclitaxel in NSCLC and most have focused on its use in combination with cisplatin. In terms of clinical efficacy, paclitaxel-cisplatin combinations achieved significantly higher response rates than teniposide plus cisplatin or etoposide plus cisplatin (previously thought to be among the more effective regimens available) in two large randomised trials. One of these studies showed a survival advantage for paclitaxel plus cisplatin [with or without a granulocyte colony-stimulating factor (G-CSF)] compared with etoposide plus cisplatin. A Canadian cost-effectiveness analysis incorporated data from one of the large randomised comparative trials and showed that the incremental cost per life-year saved for outpatient administration of paclitaxel plus cisplatin versus etoposide plus cisplatin was $US 22181 (30619 Canadian dollars; $Can) [1997 costs]. A European analysis incorporated data from the other large randomised study and showed slightly higher costs per responder for paclitaxel plus cisplatin than for teniposide plus cisplatin in The Netherlands ($US 30769 vs $US 29592) and Spain ($US 19 923 vs $US 19724) but lower costs per responder in Belgium ($US 22852 vs $US 25000) and France ($US28 080 vs $US 34747) [1995

  3. Percutaneous coronary intervention with second-generation paclitaxel-eluting stents versus everolimus-eluting stents in United States contemporary practice (REWARDS TLX Trial).

    Science.gov (United States)

    Waksman, Ron; Ghali, Magdi; Goodroe, Randy; Ryan, Thomas; Turco, Mark; Ring, Michael; McGarry, Thomas; Dobies, David; Shammas, Nicolas; Steinberg, Daniel H; Swymelar, Stacy; Kaneshige, Kimberly; Torguson, Rebecca

    2012-10-15

    Registry Experience at the Washington Hospital Center, DES - Taxus Liberte Versus Xience V (REWARDS TLX) is a physician-initiated, retrospective, real-world, multicenter, observational study for all patients >18 years of age subjected to percutaneous coronary intervention with everolimus-eluting stents (EESs) or paclitaxel-eluting stents (PESs). Outcomes of patients receiving a TAXUS Liberté or XIENCE V drug-eluting stent were compared. Baseline clinical, procedural, and follow-up data at 12 months were collected from 10 clinical centers by an electronic data capture system. The study's primary end point was major adverse cardiac events: a composite of all-cause death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. The trial is registered with http://www.clinicaltrials.gov (NCT01134159). Data were entered for 1,195 patients (PES, n = 595; EES, n = 600). Baseline clinical characteristics were similar except for higher dyslipidemia, systemic hypertension, and family history of coronary artery disease in the EES group. In-hospital outcome was similar between groups, with an overall in-hospital stent thrombosis rate of 0.2%. The primary end point at 12 months was similar (EES 7.8% vs 10.8%, p = 0.082). Overall stent thrombosis rate was lower in the EES group (0.3% vs 1.2%, respectively, p = 0.107); however, target lesion revascularization was similar (PES, hazard ratio 1.46, 95% confidence interval 0.98 to 2.19, p = 0.064). There was no difference in overall mortality between groups. In conclusion, second-generation EESs and PESs demonstrated similar efficacy and safety profiles for broadened patient and lesion subsets compared to a selected population from the pivotal trials. However, for composite efficacy and safety end points, EESs outperformed second-generation PESs. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy of breast cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Zong, Yu; Wu, Jiayi; Shen, Kunwei

    2017-03-07

    The value of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in neoadjuvant systemic therapy for breast cancer remains uncertain. Both electronic databases and proceedings of oncologic meetings were included in systematic literature search. Pooled rates of pathological complete response (pCR), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model to determine the effect of neoadjuvant nab-paclitaxel. Twenty-one studies with 2357 patients were included, 3 of which were randomized clinical trials. The aggregate pCR(ypT0/is ypN0) rate was 32% (95% CI 25-38%) in unselected breast cancer patients and variated in different subtypes. Within randomized clinical trials, the probability of achieving pCR was significantly higher in the nab-paclitaxel group than in the conventional taxanes group (OR = 1.383, 95%CI 1.141-1.676, p = 0.001). For non-hematological toxic effect, any grade and grade 3-4 peripheral sensory neuropathy occurred more frequently with nab-paclitaxel compared to paclitaxel (any grade, OR = 2.090, 95%CI 1.016-4.302, p = 0.045; grade3-4, OR = 3.766, 95%CI 2.324-6.100, p < 0.001). Hypersensitivity was more common with paclitaxel than nab-paclitaxel at any grade and grade 3-4. nab-paclitaxel is an effective cytotoxic drug in neoadjuvant treatment of breast cancer, especially for aggressive tumors in terms of pCR. Exchange of nab-paclitaxel for conventional taxanes could significantly improve pCR rate with reasonable toxicities.

  5. Comparative vascular responses three months after paclitaxel and everolimus-eluting stent implantation in streptozotocin-induced diabetic porcine coronary arteries

    Directory of Open Access Journals (Sweden)

    Sheehy Alexander

    2012-06-01

    Full Text Available Abstract Background Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES and everolimus-eluting (EES stents in a porcine coronary model of streptozotocin (STZ-induced type I diabetes. Method Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES and one Taxus Liberte (PES stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M–10-12 M after 24 hours on carotid endothelial (EC and smooth muscle (SMC cell viability under hyperglycemic (42 mM conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M for 24 hours. Results After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p vs. 0.08 ± 0.05, greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0, and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41 with PES compared to EES (p In vitro, paclitaxel significantly increased (p -7 M, while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M significantly increased caspase-3 activity (p  Conclusion After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and

  6. Paclitaxel-eluting stents versus everolimus-eluting coronary stents in a diabetic population: two-year follow-up of the TUXEDO-India trial.

    Science.gov (United States)

    Kaul, Upendra; Bhagwat, Ajit; Pinto, Brian; Goel, Praveen K; Jagtap, Prashant; Sathe, Shireesh; Wander, Gurpreet S; Arambam, Priyadarshini; Bangalore, Sripal

    2017-11-20

    The aim of this study was to report whether the superiority of the everolimus-eluting stent (EES) vs. the paclitaxel-eluting stent (PES) at one-year follow-up in the Taxus Element versus Xience Prime in a Diabetic Population (TUXEDO)-India trial was sustained at longer-term follow-up. One thousand eight hundred and thirty (1,830) patients with diabetes mellitus and coronary artery disease were randomised to EES vs. PES. Follow-up data up to two years were available in 1,701 (92.9%) patients. The primary endpoint was target vessel failure (TVF), defined as the composite of cardiac death, target vessel myocardial infarction (TV-MI), or ischaemia-driven target vessel revascularisation (TVR). Treatment with EES had a lower two-year rate of TVF (4.3% vs. 6.6%, p=0.03). Of the secondary endpoints, EES significantly reduced any MI (1.6% vs. 3.5%, p=0.01), TV-MI (0.7% vs. 3.1%, p=0.0001), ST (0.4% vs. 2.2%, p=0.001), cardiac death or target vessel MI (2.9% vs. 4.8%, p=0.04) and TLR (1.9% vs. 3.7%, p=0.02), compared with PES. Between one year and two years, no significant differences in the clinical outcomes were observed (pinteraction >0.05). In this adequately powered trial, the benefits of EES vs. PES in a diabetic population seen at one year were maintained at two years.

  7. Clopidogrel paclitaxel drug-drug interaction

    DEFF Research Database (Denmark)

    Agergaard, K; Mau-Sørensen, M; Stage, T B

    2017-01-01

    register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age and sex matched controls treated with paclitaxel and low dose aspirin. By a cumulative dose of 1500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard...... ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% CI, 0.9-3.0). Among those receiving a high dose paclitaxel regimen, the hazard ratio was 2.3 (95% CI, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy......Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-β-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription...

  8. Paclitaxel Albumin-stabilized Nanoparticle Formulation

    Science.gov (United States)

    This page contains brief information about paclitaxel albumin-stabilized nanoparticle formulation and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  9. Phase II Trial of Adjuvant Pelvic Radiation “Sandwiched” Between Combination Paclitaxel and Carboplatin in Women with Uterine Papillary Serous Carcinoma

    Science.gov (United States)

    Einstein, Mark H.; Frimer, Marina; Kuo, Dennis Y-S; Reimers, Laura L.; Mehta, Keyur; Mutyala, Subhakar; Huang, Gloria S.; Hou, June Y.; Goldberg, Gary L.

    2013-01-01

    Objective To evaluate the safety and survival in women treated with adjuvant pelvic radiation “sandwiched” between six cycles of paclitaxel and carboplatin chemotherapy with completely resected UPSC. Methods Surgically staged women with UPSC (FIGO stage 1-4) and no visible residual disease were enrolled. Treatment involved paclitaxel (175 mg/m2) and carboplatin (AUC=6.0-7.5) every 21 days for 3 doses, followed by radiation therapy (RT), followed by an additional 3 cycles of paclitaxel and carboplatin (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least 3 cycles of chemotherapy and RT. Results A total of 81 patients were enrolled, of which 72 patients completed the first 3 cycles of chemotherapy followed by prescribed RT. Median age was 67 years (range: 43–82 years). 59/72 (82%) had disease confined to the uterus and 13/72 (18%) had completely resected extra-uterine disease (stage 3&4). 65 (83%) completed the protocol. Overall PFS and OS for combined stage 1&2 patients was 65.5±3.6 months and 76.5±4.3 months, respectively. PFS and OS for combined stage 3&4 patients was 25.8±3.0 and 35.9±5.3 months, respectively. Three-year % survival probability for stage 1&2 patients was 84% and for stage 3&4 patients was 50%. Of the 435 chemotherapy cycles administered, there were 11(2.5%) G3/G4 non-hematologic toxicities. 26(6.0%) cycles had dose reductions and 37(8.5%) had dose delays. Conclusions Compared to prior studies of single modality adjuvant therapy, RT “sandwiched” between paclitaxel and carboplatin chemotherapy is well-tolerated and highly efficacious in women with completely resected UPSC. PMID:22035806

  10. Rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: Two-year clinical outcome of the randomized ROTAXUS trial.

    Science.gov (United States)

    de Waha, Suzanne; Allali, Abdelhakim; Büttner, Heinz-Joachim; Toelg, Ralph; Geist, Volker; Neumann, Franz-Josef; Khattab, Ahmed A; Richardt, Gert; Abdel-Wahab, Mohamed

    2016-03-01

    In the randomized ROTAXUS trial, routine lesion preparation of complex calcified coronary lesions using rotational atherectomy (RA) prior to paclitaxel-eluting stent implantation did not reduce the primary endpoint of angiographic late lumen loss at 9 months compared to stenting without RA. So far, no long-term data of prospective head-to-head comparisons between both treatment strategies have been reported. ROTAXUS randomly assigned patients with complex calcified coronary lesions to RA followed by stenting (n = 120) or stenting without RA (n = 120). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events (MACE) at 2-year follow-up defined as the composite of death, myocardial infarction, and target vessel revascularization (TVR). At 2 years, MACE occurred in 32 patients in the RA group and 37 patients in the standard therapy group (29.4% vs. 34.3%, P = 0.47). The rates of death (8.3% vs. 7.4%, P = 1.00), myocardial infarction (8.3% vs. 6.5%, P = 0.80), target lesion revascularization (TLR, 13.8% vs. 16.7%, P = 0.58), and TVR (19.3% vs. 22.2%, P = 0.62) were similar in both groups. Despite high rates of initial angiographic success, nearly one third of patients enrolled in ROTAXUS experienced MACE within 2-year follow-up, with no differences between patients treated with or without RA. © 2015 Wiley Periodicals, Inc.

  11. Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

    Science.gov (United States)

    Young, M; Plosker, G L

    2001-01-01

    Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life

  12. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    Science.gov (United States)

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

  13. Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials

    DEFF Research Database (Denmark)

    Juul, Nicolai Stefan; Szallasi, Zoltan Imre; Eklund, Aron Charles

    2010-01-01

    -negative breast cancer. METHODS: We derived a paclitaxel response metagene based on mitotic and ceramide genes identified by functional genomics studies. We used area under the curve (AUC) analysis and multivariate logistic regression to retrospectively assess the metagene in six cohorts of patients with triple......-paclitaxel treated cohorts (0.53 [0.31-0.77], 0.59 [0.22-0.82], 0.53 [0.36-0.71], 0.64 [0.43-0.81]). In multivariate logistic regression, the metagene was associated with pCR (OR 19.92, 2.62-151.57; p=0.0039) with paclitaxel-containing chemotherapy. INTERPRETATION: The paclitaxel response metagene shows promise...... as a paclitaxel-specific predictor of pCR in patients with triple-negative breast cancer. The metagene is suitable for development into a reverse transcription-PCR assay, for which clinically relevant thresholds could be established in randomised clinical trials. These results highlight the potential...

  14. Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I-II trial

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnt, T.; Pigorsch, S.; Pelz, T.; Haensgen, G.; Dunst, J. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Becker, A. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Dept. of Radiotherapy, Municipial Hospital, Dessau (Germany); Bloching, M.; Passmann, M. [Dept. of Head and Neck Surgery, Martin Luther Univ., Halle (Germany); Lotterer, E. [Dept. of Internal Medicine I, Martin Luther Univ., Halle (Germany)

    2003-10-01

    We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m{sup 2} on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m{sup 2} twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 {+-} 61 cm{sup 3}. The mean follow-up was 30 months (range 4-39 months). Results: One early death (peritonitis and sepsis a t day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m{sup 2} paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m{sup 2} twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30

  15. Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I-II trial

    International Nuclear Information System (INIS)

    Kuhnt, T.; Pigorsch, S.; Pelz, T.; Haensgen, G.; Dunst, J.; Becker, A.; Bloching, M.; Passmann, M.; Lotterer, E.

    2003-01-01

    We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m 2 on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m 2 twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 ± 61 cm 3 . The mean follow-up was 30 months (range 4-39 months). Results: One early death (peritonitis and sepsis a t day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m 2 paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m 2 twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30 of neutropenic infection

  16. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

    Science.gov (United States)

    Mok, Tony S; Wu, Yi-Long; Thongprasert, Sumitra; Yang, Chih-Hsin; Chu, Da-Tong; Saijo, Nagahiro; Sunpaweravong, Patrapim; Han, Baohui; Margono, Benjamin; Ichinose, Yukito; Nishiwaki, Yutaka; Ohe, Yuichiro; Yang, Jin-Ji; Chewaskulyong, Busyamas; Jiang, Haiyi; Duffield, Emma L; Watkins, Claire L; Armour, Alison A; Fukuoka, Masahiro

    2009-09-03

    Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for

  17. Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials.

    Science.gov (United States)

    Juul, Nicolai; Szallasi, Zoltan; Eklund, Aron C; Li, Qiyuan; Burrell, Rebecca A; Gerlinger, Marco; Valero, Vicente; Andreopoulou, Eleni; Esteva, Francisco J; Symmans, W Fraser; Desmedt, Christine; Haibe-Kains, Benjamin; Sotiriou, Christos; Pusztai, Lajos; Swanton, Charles

    2010-04-01

    Addition of taxanes to preoperative chemotherapy in breast cancer increases the proportion of patients who have a pathological complete response (pCR). However, a substantial proportion of patients do not respond, and the prognosis is particularly poor for patients with oestrogen-receptor (ER)/progesterone-receptor (PR)/human epidermal growth factor receptor 2 (HER2; ERBB2)-negative (triple-negative) disease who do not achieve a pCR. Reliable identification of such patients is the first step in determining who might benefit from alternative treatment regimens in clinical trials. We previously identified genes involved in mitosis or ceramide metabolism that influenced sensitivity to paclitaxel, with an RNA interference (RNAi) screen in three cancer cell lines, including a triple-negative breast-cancer cell line. Here, we assess these genes as a predictor of pCR to paclitaxel combination chemotherapy in triple-negative breast cancer. We derived a paclitaxel response metagene based on mitotic and ceramide genes identified by functional genomics studies. We used area under the curve (AUC) analysis and multivariate logistic regression to retrospectively assess the metagene in six cohorts of patients with triple-negative breast cancer treated with neoadjuvant chemotherapy; two cohorts treated with paclitaxel (n=27, 30) and four treated without paclitaxel (n=88, 28, 48, 39). The metagene was associated with pCR in paclitaxel-treated cohorts (AUC 0.79 [95% CI 0.53-0.93], 0.72 [0.48-0.90]) but not in non-paclitaxel treated cohorts (0.53 [0.31-0.77], 0.59 [0.22-0.82], 0.53 [0.36-0.71], 0.64 [0.43-0.81]). In multivariate logistic regression, the metagene was associated with pCR (OR 19.92, 2.62-151.57; p=0.0039) with paclitaxel-containing chemotherapy. The paclitaxel response metagene shows promise as a paclitaxel-specific predictor of pCR in patients with triple-negative breast cancer. The metagene is suitable for development into a reverse transcription-PCR assay, for which

  18. An everolimus-eluting stent versus a paclitaxel-eluting stent in small vessel coronary artery disease: a pooled analysis from the SPIRIT II and SPIRIT III trials.

    Science.gov (United States)

    Bartorelli, Antonio L; Serruys, Patrick W; Miquel-Hébert, Karine; Yu, Shui; Pierson, Wes; Stone, Gregg W

    2010-07-01

    To evaluate the safety and efficacy of the XIENCE V everolimus-eluting stent compared to the TAXUS paclitaxel-eluting stent in small vessels. The XIENCE V everolimus-eluting stent (EES) has been shown to improve angiographic and clinical outcomes after percutaneous myocardial revascularization, but its performance in small coronary arteries has not been investigated. In this pooled analysis, we studied a cohort of 541 patients with small coronary vessels (reference diameter SPIRIT II and SPIRIT III studies. TAXUS Express (73% of lesions) and TAXUS Liberté (27% of lesions) paclitaxel-eluting stents (PES) were used as controls in SPIRIT II. In SPIRIT III, Taxus Express(2) PES was the control. Mean angiographic in-stent and in-segment late loss was significantly less in the EES group compared with the PES group, (0.15 +/- 0.37 mm vs. 0.30 +/- 0.44 mm; P = 0.011 for in-stent; 0.10 +/- 0.38 mm vs. 0.21 +/- 0.34 mm; P = 0.034 for in-segment). EES also resulted in a significant reduction in composite major adverse cardiac events at 1 year (19/366 [5.2%] vs. 17/159 [10.7%]; P = 0.037), due to fewer non-Q-wave myocardial infarctions and target lesion revascularizations. At 1 year, the rate of non-Q-wave myocardial infarction was significantly lower in the EES group compared with that of the PES group (6/366 [1.6%] vs. 8/159 [5.0%]; P = 0.037). In patients with small vessel coronary arteries, the XIENCE V EES was superior to the TAXUS PES. (c) 2010 Wiley-Liss, Inc.

  19. 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

  20. An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) versus conventional paclitaxel for metastatic breast cancer patients: the COSTANza study

    Science.gov (United States)

    Lazzaro, Carlo; Bordonaro, Roberto; Cognetti, Francesco; Fabi, Alessandra; De Placido, Sabino; Arpino, Grazia; Marchetti, Paolo; Botticelli, Andrea; Pronzato, Paolo; Martelli, Elisa

    2013-01-01

    Purpose Paclitaxel albumin (nab-paclitaxel) is a nanoparticle albumin-bound paclitaxel formulation aimed at increasing therapeutic index in metastatic breast cancer. When compared to conventional paclitaxel, nab-paclitaxel has a reported longer time to progression, higher response, lower incidence of neutropenia, no need for premedication, shorter time of administration, and in pretreated metastatic breast cancer patients, extended overall survival. This study investigates the cost-effectiveness of nab-paclitaxel versus conventional paclitaxel for pretreated metastatic breast cancer patients in Italy. Materials and methods A Markov model with progression-free, progressed, and dead states was developed to estimate costs, outcomes, and quality adjusted life years over 5 years from the Italian National Health Service viewpoint. Patients were assumed to receive nab-paclitaxel 260 mg/m2 three times weekly or conventional paclitaxel 175 mg/m2 three times weekly. Data on health care resource consumption was collected from a convenience sample of five Italian centers. Resources were valued at Euro (€) 2011. Published utility weights were applied to health states to estimate the impact of response, disease progression, and adverse events on quality adjusted life years. Three sensitivity analyses tested the robustness of the base case incremental cost-effectiveness ratio (ICER). Results and conclusion Compared to conventional paclitaxel, nab-paclitaxel gains an extra 0.165 quality adjusted life years (0.265 life years saved) and incurs additional costs of €2506 per patient treated. This translates to an ICER of €15,189 (95% confidence interval: €11,891–€28,415). One-way sensitivity analysis underscores that ICER for nab-paclitaxel remains stable despite varying taxanes cost. Threshold analysis shows that ICER for nab-paclitaxel exceeds €40,000 only if cost per mg of conventional paclitaxel is set to zero. Probabilistic sensitivity analysis highlights that nab-paclitaxel

  1. A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial.

    Science.gov (United States)

    Bachet, Jean-Baptiste; Chibaudel, Benoist; Bonnetain, Franck; Validire, Pierre; Hammel, Pascal; André, Thierry; Louvet, Christophe

    2015-10-06

    Metastatic pancreatic adenocarcinoma (PAC) prognosis remains dismal and gemcitabine monotherapy has been the standard treatment over the last decade. Currently, two first-line regimens are used in this setting: FOLFIRINOX and nab-paclitaxel plus gemcitabine. Increasing translational data on the predictive value of hENT1 for determining gemcitabine efficacy suggest that a non-gemcitabine-based regimen is favored in about 60 % of patients with PAC due to high resistance of PAC to this cytotoxic drug. This study aims to evaluate the efficacy of weekly nab-paclitaxel combined with gemcitabine or a simplified (s) LV5FU2 regimen in patients with previously untreated metastatic PAC. AFUGEM is a two-stage, open-label, randomized, multicenter, phase II trial. Patients with PAC who meet the inclusion criteria and provide written informed consent will be randomized in a 1:2 ratio to either nab-paclitaxel (125 mg/m(2)) plus gemcitabine (1000 mg/m(2)) given on days 1, 8, and 15 every 28 days or nab-paclitaxel (125 mg/m(2)) plus sLV5FU2 (leucovorin 400 mg/m(2) followed by bolus 400 mg/m(2) 5-fluorouracil and by 5-fluorouracil 2400 mg/m(2) as an 46-h intravenous infusion) given on days 1 and 15 every 28 days. A total of 114 patients will be randomized to one of the treatment arms. The primary endpoint is progression-free survival at 4 months. Secondary outcomes are rate and duration of response, disease control, overall survival, safety, and quality of life. Potential biomarkers of gemcitabine (hENT1, dCK) and 5-fluorouracil (TS) efficacy will be assessed. The AFUGEM trial is designed to provide valuable information regarding efficacy and tolerability of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus sLV5FU2 regimens. Identification of potential predictive biomarkers of gemcitabine and 5-fluorouracil is likely to drive therapeutic decisions in patients with metastatic PAC. AFUGEM is registered at Clinicaltrials.gov: NCT01964534 , October 15, 2013.

  2. Long-term follow-up of a phase I/II trial of dose escalating three-dimensional conformal thoracic radiation therapy with induction and concurrent carboplatin and paclitaxel in unresectable stage IIIA/B non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Lee, Carrie B; Moore, Dominic T; Rivera, M Patricia; Halle, Jan; Limentani, Steven; Rosenman, Julian G; Socinski, Mark A

    2008-11-01

    We conducted a modified phase I/II trial investigating the incorporation of three-dimensional conformal thoracic radiation therapy (TCRT) into the treatment paradigm of induction and concurrent carboplatin and paclitaxel in patients with unresectable stage IIIA/B non-small cell lung cancer. Patients received 2 cycles of induction carboplatin (area under the curve of 6) and paclitaxel (225 mg/m) on days 1, and 22. On day 43 concurrent TCRT and weekly x6 of carboplatin (area under the curve = 2) and paclitaxel (45 mg/m) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy), and the 74 Gy cohort was expanded into a phase II trial. Sixty-two patients were enrolled; the median age 57 years (range, 36-82), 39 were male (63%), 61 (98%) had a performance status of 0 or 1, 28 (45%) had stage IIIA disease, 21 (34%) had >5% weight loss, and the median forced expiratory volume 1 = 2.10 liters (range, 1.02-3.75). With a median follow-up for survivors of approximately 9 years (range, 7-11 years) the median progression-free survival, time to tumor progression, and overall survival (OS) (with 95% confidence intervals) were 10 (8.5-17), 15 (9-50), and 25 months (18-37), respectively. The 5-year progression-free survival and OS rates were 21% (12-32%) and 27% (17-39%), respectively. The 10-year OS rate was 14% (7-25%). The long term survival rate compares favorably to other treatment approaches for stage III non-small cell lung cancer.

  3. Concurrent paclitaxel and radiotherapy. Treatment feasibility studies

    International Nuclear Information System (INIS)

    Vogt, H.G.; Martin, T.; Kolotas, C.; Hey, S.; Schneider, L.; Templin, T.; Zamboglou, N.; Dornoff, W.; Kettner, H.

    1997-01-01

    Background: The anti-neoplastic effect of paclitaxel has been demonstrated in various clinical studies in different malignant diseases. Clinical studies have also demonstrated a greater efficacy for simultaneous radio-chemotherapy compared with radiotherapy alone when using radiosensitizing drugs. Based on these clinical and in-vitro data we initiated several pilot studies using paclitaxel as a radiosensitizing agent and we now present our initial experience in its use in a combined modality protocol, radiation and simultaneous chemotherapy with paclitaxel. Methods: I. Concurrent paclitaxel and radiation for locally advanced non-small-cell lung cancer (NSCLC): In a phase-I-study we applicated paclitaxel (45 to 65 mg/m 2 ) as a 3-hour infusion weekly for 3 to 7 weeks simultaneously with primary radiotherapy in shrinking field technique with 5x1.8 Gy/week up to 59.4 Gy. - II. Concurrent paclitaxel and radiation for breast cancer as neoadjuvant or palliative: 50 mg/m 2 paclitaxel as a 3-hour infusion weekly for 6 weeks simultaneous with neoadjuvant or palliative radiotherapy of the breast/chest wall with 5x1.8 Gy/week up to 54.0 Gy. - III./IV. Concurrent paclitaxel/carboplatin and combined radiation (EBRT+brachytherapy) for locally advanced inoperable cancer of the cervix: 50 mg/m 2 paclitaxel as a 3-hour infusion weekly for 5 weeks, 50 mg/m 2 carboplatin at day 1 to 5 in week 1 and 5 simultaneously with external beam radiotherapy of the pelvis with 5x1.8 Gy/week up to 54.0 Gy and endocavitary LDR-brachytherapy (4x5 Gy). - V. Concurrent paclitaxel and radiation for locally advanced inoperable cancer of the bladder: 50 mg/m 2 paclitaxel as a 3-hour infusion weekly for 5 weeks simultaneous with radiotherapy of the pelvis with 5x1.8 Gy/week up to 50.4 Gy. VI. Concurrent paclitaxel and radiation in locally advanced inoperable head and neck cancer: 50 mg/m 2 paclitaxel as a 3-hour infusion weekly for 7 to 8 weeks simultaneous with radiotherapy in shrinking field technique

  4. Albumin-bound paclitaxel in solid tumors: clinical development and future directions.

    Science.gov (United States)

    Kundranda, Madappa N; Niu, Jiaxin

    2015-01-01

    Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel's indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.

  5. Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial

    DEFF Research Database (Denmark)

    Galløe, Anders M; Thuesen, Leif; Kelbaek, Henning

    2008-01-01

    Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients.......Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients....

  6. Prodrug Strategies for Paclitaxel

    Directory of Open Access Journals (Sweden)

    Ziyuan Meng

    2016-05-01

    Full Text Available Paclitaxel is an anti-tumor agent with remarkable anti-tumor activity and wide clinical uses. However, it is also faced with various challenges especially for its poor water solubility and low selectivity for the target. To overcome these disadvantages of paclitaxel, approaches using small molecule modifications and macromolecule modifications have been developed by many research groups from all over the world. In this review, we discuss the different strategies especially prodrug strategies that are currently used to make paclitaxel more effective.

  7. Nano-particle nab-paclitaxel in treatment of metastatic breast cancer

    International Nuclear Information System (INIS)

    Barilla, R.; Dolinsky, J.

    2011-01-01

    Taxanes, paclitaxel and docetaxel, are together with anthracyclines the cornerstone of treatment of both early and advanced breast cancer. They are established as the standard of care either as monotherapy or in combination with other cytostatic agents and targeted therapies. However, despite their significant clinical activity in many cancer types, the use of taxanes is often limited by significant toxicities, including hypersensitivity reactions, which complicate treatment and diminish quality of life. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a 130 nm particle cremophor free formulation. Due to its special properties it allows to reach higher intratumoral concentrations of paclitaxel. In randomized phase II and phase III trials has been shown a superior efficacy and safety of nab-paclitaxel over paclitaxel or docetaxel. This new therapeutic formulation of paclitaxel may be therefore an adequate alternative to classic formulation of taxanes in the treatment of metastatic breast cancer. (author)

  8. Multicenter Phase II Study with Weekly Bendamustine and Paclitaxel as First- or Later-Line Therapy in Patients with Metastatic Breast Cancer: RiTa II Trial.

    Science.gov (United States)

    Loibl, Sibylle; Doering, Gabriele; Müller, Lothar; Grote-Metke, Albert; Müller, Roberto; Tomé, Oliver; Wiest, Wolfgang; Maisch, Andrea; Nekljudova, Valentina; von Minckwitz, Gunter

    2011-12-01

    The combination of bendamustine (B) and paclitaxel (P) as anthracycline-free treatment option in patients with advanced breast cancer has been evaluated in the previous RiTa I trial. The regimen of weekly B 70 mg/m(2) and P 90 mg/m(2) with a pause every 4th week was established as an effective regimen with low toxicity. The aim of the present RiTa II study was to investigate the potential of BP as anthracycline-free combination therapy. The primary objective was to determine the progression-free survival (PFS); secondary endpoints were safety, tolerability, overall response rate (ORR) and overall survival (OS). 26 patients were available, 15 received BP as first-line, 11 as beyond first-line treatment. 27% patients had triple-negative breast cancer (TNBC). Median PFS and OS were 7.3 months (95% confidence interval (CI): 5.5-10.9) and 14.9 months (95% CI: 9.9-22.9), respectively. The 1-year PFS rate was 20.3% and the 1-year OS rate 71.2%. The ORR was 42.3%, including 4 complete and 7 partial remissions. TNBC patients reached an ORR of 71.4%. Anthracycline-pretreated patients showed an ORR of 43.8%, confirming bendamustine's lack of cross-resistance to anthracycline agents. BP represents a favorable option with moderate toxicity in pretreated metastatic breast cancer and offers a possibility for application in anthracycline-pretreated and TNBC patients.

  9. Clinical Pharmacokinetics of Paclitaxel Monotherapy

    DEFF Research Database (Denmark)

    Stage, Tore B; Bergmann, Troels K; Kroetz, Deanna L

    2018-01-01

    Paclitaxel is an anticancer agent efficacious in the treatment of ovarian, breast, and lung cancer. Due to a strong link between the pharmacokinetics and therapeutic efficacy of paclitaxel, we reviewed the literature on paclitaxel pharmacokinetics. Systematic data mining was performed to extract ...

  10. Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation

    Directory of Open Access Journals (Sweden)

    Abdel Kader Y

    2013-07-01

    Full Text Available Yasser Abdel Kader,1 Thierry Le Chevalier,2 Tamer El-Nahas,1 Amr Sakr11Department of Clinical Oncology, Cairo University, Cairo, Egypt; 2Department of Medical Oncology, Institut Gustave Roussy, Villejuif, Paris, FrancePurpose: The majority of Egyptian patients with lung cancer present at a late stage of the disease. Bevacizumab/carboplatin/paclitaxel, as well as cisplatin plus pemetrexed, are both standard regimens for advanced non-squamous bronchogenic cancer. This study compares both regimens, in terms of efficacy and toxicity profile, in Egyptian patients.Patients and methods: This is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïve patients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m2 on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and paclitaxel 60 mg/m2 on Day 1, Day 8, and Day 15 every 4 weeks. In the second group, patients received cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks.Results: The combination of bevacizumab/carboplatin/paclitaxel demonstrated higher Grade III–IV toxicity than cisplatin/pemetrexed regarding sensory/motor neuropathy (P = 0.06, DVT (P = 0.23, proteinuria (P = 0.23, and hypertension (P = 0.11, as well as Grade II alopecia (P = 0.001; however, no significant difference in toxicities between both arms was recorded regarding nausea and vomiting (P = 0.66, hematological toxicity, febrile neutropenia (P = 1 and fatigue (P = 0.66. Progression-free survival was similar for both treatment arms with a median of 6 months (P = 0.978. Overall median survival was comparable in both arms, 16.07 months versus 16.01 months (P = 0.89.Conclusion: Bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed provided meaningful and comparable efficacy

  11. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Terence, E-mail: trdtwk@nccs.com.sg [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Lim, Wan-Teck [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Ong, Whee-Sze; Tan, Sze-Huey [Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore (Singapore); Yip, Connie; Quah, Daniel [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Soo, Khee-Chee [Division of Surgical Oncology, National Cancer Centre Singapore (Singapore); Wee, Joseph [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore)

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  12. Paclitaxel, cisplatin, 5-fluorouracil and radiotherapy in the management of advanced squamous cell carcinoma of the head and neck. A phase II trial

    International Nuclear Information System (INIS)

    Merlano, Marco; Russi, Elvio G.; Numico, Gianmauro; Colantonio, Ida; Garrone, Ornella; Pelissero, Antonio; Granetto, Cristina; Gasco, Milena; Di Costanzo, Gianna; Heouaine, Abdelhamid; Vigna Taglianti, Riccardo; Cipolat, Marco

    2005-01-01

    Aim of the present study was to test, activity and toxicity of a rapidly alternating chemoradiation (paclitaxel based) in 31 patients with unresectable, locally advanced or recurrent after surgery, head and neck cancer. Three-year overall survival and progression-free survival were 61.4 and 73.7%, respectively. Main side effects remain a major problem

  13. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy

    DEFF Research Database (Denmark)

    Bellmunt, Joaquim; von der Maase, Hans; Mead, Graham M

    2012-01-01

    The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival....

  14. Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trial in Ovarian cancer (MITO-4 retrospective study

    Directory of Open Access Journals (Sweden)

    Danese Saverio

    2006-01-01

    Full Text Available Abstract Background Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. Methods 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial. All patients received carboplatin (AUC 5 plus paclitaxel (175 mg/m2 every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria. Results 55 patients (46% did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54% had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23% referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months: 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77% had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%, between 2 and 6 months in 15 (25%, or after more than 6 months in 9 patients (15%. Considering all 120 treated patients

  15. Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study

    International Nuclear Information System (INIS)

    Pignata, Sandro; Manzione, Luigi; Cartenì, Giacomo; Nardi, Mario; Danese, Saverio; Valerio, Maria Rosaria; Matteis, Andrea de; Massidda, Bruno; Gasparini, Giampietro; Di Maio, Massimo; Pisano, Carmela; De Placido, Sabino; Perrone, Francesco; Biamonte, Rosalbino; Scambia, Giovanni; Di Vagno, Giovanni; Colucci, Giuseppe; Febbraro, Antonio; Marinaccio, Marco; Vernaglia Lombardi, Alessandra

    2006-01-01

    Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m 2 ) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria. 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent

  16. Randomized trial of Legflow® paclitaxel eluting balloon and stenting versus standard percutaneous transluminal angioplasty and stenting for the treatment of intermediate and long lesions of the superficial femoral artery (RAPID trial): Study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    A. Karimi; S.W. de Boer (Sanne W.); D.A.F. Van Den Heuvel; B. Fioole (Bram); D. Vroegindeweij (Dammis); J.M.M. Heyligers (Jan); P.N.M. Lohle (Paul N.M.); O.E. Elgersma (Otto E.); R.P.T. Nolthenius (Rudolf ); J.A. Vos (Jan Albert); J.-P.P.M. de Vries (Jean-Paul)

    2013-01-01

    textabstractBackground: Restenosis after percutaneous transluminal angioplasty (PTA) of the superficial femoral artery (SFA) may occur in 45% of patients at 2 years follow-up. Paclitaxel-coated balloons have been found to reduce neointimal hyperplasia, and thus reduce restenosis. Recently, the

  17. Randomized trial of Legflow((R)) paclitaxel eluting balloon and stenting versus standard percutaneous transluminal angioplasty and stenting for the treatment of intermediate and long lesions of the superficial femoral artery (RAPID trial): study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Karimi, A.; Boer, S.W. de; Heuvel, D.A. Van Den; Fioole, B.; Vroegindeweij, D.; Heyligers, J.M.M; Lohle, P.N.; Elgersma, O.; Nolthenius, R.P.T.; Vos, J.A.; Vries, J.P. de

    2013-01-01

    BACKGROUND: Restenosis after percutaneous transluminal angioplasty (PTA) of the superficial femoral artery (SFA) may occur in 45% of patients at 2 years follow-up. Paclitaxel-coated balloons have been found to reduce neointimal hyperplasia, and thus reduce restenosis. Recently, the Legflow((R))

  18. Randomized Phase II Trial of Erlotinib Alone or With Carboplatin and Paclitaxel in Patients Who Were Never or Light Former Smokers With Advanced Lung Adenocarcinoma: CALGB 30406 Trial

    Science.gov (United States)

    Jänne, Pasi A.; Wang, Xiaofei; Socinski, Mark A.; Crawford, Jeffrey; Stinchcombe, Thomas E.; Gu, Lin; Capelletti, Marzia; Edelman, Martin J.; Villalona-Calero, Miguel A.; Kratzke, Robert; Vokes, Everett E.; Miller, Vincent A.

    2012-01-01

    Purpose Erlotinib is clinically effective in patients with non–small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics. Patients and Methods Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and ≤ 10 pack years and quit ≥ 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory. Results PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P < .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP. Conclusion Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit. PMID:22547605

  19. Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naïve non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcinoma or mutated EGFR

    International Nuclear Information System (INIS)

    Choi, Yoon Ji; Lee, Dae Ho; Choi, Chang Min; Lee, Jung Shin; Lee, Seung Jin; Ahn, Jin-Hee; Kim, Sang-We

    2015-01-01

    Considering cell cycle dependent cytotoxicity, intercalation of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may be a treatment option in non-small cell lung cancer (NSCLC). This randomized phase 2 study compared the efficacy of paclitaxel and carboplatin (PC) intercalated with gefitinib (G) versus PC alone in a selected, chemotherapy-naïve population of advanced NSCLC patients with a history of smoking or wild-type EGFR. Eligible patients were chemotherapy-naïve advanced NSCLC patients with Eastern Cooperative Oncology Group performance status of 0—2. Non-smoking patients with adenocarcinoma or patients with activating EGFR mutation were excluded because they could benefit from gefitinib alone. Eligible patients were randomized to one of the following treatment arms: PCG, P 175 mg/m 2 , and C AUC 5 administered intravenously on day 1 intercalated with G 250 mg orally on days 2 through 15 every 3 weeks for four cycles followed by G 250 mg orally until progressive disease; or PC, same dosing schedule for four cycles only. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profile. A total of 90 patients participated in the study. The ORRs were 41.9 % (95 % confidence interval (CI) 27.0–57.9 %) for the PCG arm and 39.5 % (95 % CI 25.0–55.6 %) for the PC arm (P = 0.826). No differences in PFS (4.1 vs. 4.1 months, P = 0.781) or OS (9.3 vs. 10.5 months, P = 0.827) were observed between the PCG and PC arms. Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity. Rash and pruritus were more frequent in the PCG than in the PC arm. PCG did not improve ORR, PFS, and OS compared to PC chemotherapy alone for NSCLC in a clinically selected population excluding non-smoking adenocarcinoma or mutated EGFR. The study is registered with ClinicalTrials.gov (NCT01196234). Registration date is 08/09/2010

  20. Safety results from a phase III study (TURANDOT trial by CECOG) of first-line bevacizumab in combination with capecitabine or paclitaxel for HER-2-negative locally recurrent or metastatic breast cancer.

    Science.gov (United States)

    Lang, I; Inbar, M J; Kahán, Z; Greil, R; Beslija, S; Stemmer, S M; Kaufman, B; Zvirbule, Z; Steger, G G; Messinger, D; Brodowicz, T; Zielinski, C

    2012-11-01

    We report safety data from a randomised, phase III study (CECOG/BC.1.3.005) evaluating first-line bevacizumab plus paclitaxel or capecitabine for locally recurrent or metastatic breast cancer. Patients aged ≥18 years with human epidermal growth factor receptor-2-negative breast adenocarcinoma were randomised to Arm A: bevacizumab 10 mg/kg days 1 and 15; paclitaxel 90 mg/m(2) days 1, 8, and 15, every 4 weeks; or Arm B: bevacizumab 15 mg/kg day 1; capecitabine 1000 mg/m(2) b.i.d., days 1-14, every 3 weeks, until disease progression, unacceptable toxicity or consent withdrawal. A post hoc interim safety analysis included 561 patients (Arm A: 284, Arm B: 277). The regimens demonstrated similar frequencies of all-grade and serious adverse events (SAEs), but different safety profiles. Treatment-related events occurred in 85.2% (Arm A) and 78.0% (Arm B) of patients. Fatigue was most common in Arm A (30.6% versus 23.5% Arm B), and hand-foot syndrome (HFS) most common in Arm B (49.5% versus 2.5% Arm A). Diarrhoea (Arm A: 0.4%, Arm B: 1.4%) and pulmonary embolism (Arm A: 0.7%, Arm B: 1.1%) were the most frequently reported SAEs. These findings are in-line with safety data for bevacizumab plus paclitaxel or capecitabine, reported in previous phase III trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Autophagy promotes paclitaxel resistance of cervical cancer cells: involvement of Warburg effect activated hypoxia-induced factor 1-?-mediated signaling

    OpenAIRE

    Peng, X; Gong, F; Chen, Y; Jiang, Y; Liu, J; Yu, M; Zhang, S; Wang, M; Xiao, G; Liao, H

    2014-01-01

    Paclitaxel is one of the most effective chemotherapy drugs for advanced cervical cancer. However, acquired resistance of paclitaxel represents a major barrier to successful anticancer treatment. In this study, paclitaxel-resistant HeLa sublines (HeLa-R cell lines) were established by continuous exposure and increased autophagy level was observed in HeLa-R cells. 3-Methyladenine or ATG7 siRNA, autophagy inhibitors, could restore sensitivity of HeLa-R cells to paclitaxel compared with parental ...

  2. Long-Term Follow-Up of a Prospective Trial of Trimodality Therapy of Weekly Paclitaxel, Radiation, and Androgen Deprivation in High-Risk Prostate Cancer With or Without Prior Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Arif, E-mail: ahussain@som.umaryland.edu [University of Maryland Greenebaum Cancer Center, Baltimore, MD (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (United States); Baltimore VA Medical Center, Baltimore, MD (United States); Wu, Yin [Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (United States); Mirmiran, Alireza [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); DiBiase, Steven [Cooper University Hospital, Camden, NJ (United States); Goloubeva, Olga [University of Maryland Greenebaum Cancer Center, Baltimore, MD (United States); Bridges, Benjamin [University of Maryland Greenebaum Cancer Center, Baltimore, MD (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (United States); Mannuel, Heather [University of Maryland Greenebaum Cancer Center, Baltimore, MD (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (United States); Baltimore VA Medical Center, Baltimore, MD (United States); Engstrom, Christine [Baltimore VA Medical Center, Baltimore, MD (United States); Dawson, Nancy [Lombardi Cancer Center, Georgetown University, Washington, D.C (United States); Amin, Pradip; Kwok, Young [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2012-01-01

    Purpose: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) {>=}0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m{sup 2}/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Results: Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m{sup 2}/week in RP patients and 60 mg/m{sup 2}/week in LAPC patients is

  3. Long-Term Follow-Up of a Prospective Trial of Trimodality Therapy of Weekly Paclitaxel, Radiation, and Androgen Deprivation in High-Risk Prostate Cancer With or Without Prior Prostatectomy

    International Nuclear Information System (INIS)

    Hussain, Arif; Wu, Yin; Mirmiran, Alireza; DiBiase, Steven; Goloubeva, Olga; Bridges, Benjamin; Mannuel, Heather; Engstrom, Christine; Dawson, Nancy; Amin, Pradip; Kwok, Young

    2012-01-01

    Purpose: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) ≥0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8–10; 3) GS 7 + PSA 10–20 ng/mL; or 4) PSA 20–150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m 2 /wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Results: Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45–86 years), PSA 5.9 (0.1–92.1 ng/mL), GS 8 (6–9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8–82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m 2 /week in RP patients and 60 mg/m 2 /week in LAPC patients is

  4. A comparative study of the effects of vitamin C, sirolimus, and paclitaxel on the growth of endothelial and smooth muscle cells for cardiovascular medical device applications

    Directory of Open Access Journals (Sweden)

    Kakade S

    2013-06-01

    Full Text Available Sandeep Kakade, Gopinath ManiBiomedical Engineering Program, The University of South Dakota, Sioux Falls, SD, USAAbstract: Antiproliferative drugs such as sirolimus (SIR and paclitaxel (PAT are currently released from stents and vascular grafts to inhibit the growth of smooth muscle cells (SMCs, thereby preventing neointimal hyperplasia. However, these drugs delay or impair the growth of endothelial cells (ECs on implant surfaces causing late thrombosis. Hence, there is a need to use alternative drugs in these implants to encourage the growth of ECs and to inhibit the growth of SMCs. Vitamin C (L-ascorbic acid [L-AA] is one such drug which has been shown to encourage EC growth and inhibit SMC growth when orally administered or added directly to the cell cultures. In this research, four sets of in vitro cell culture experiments were carried out to compare the effects of L-AA, SIR, and PAT on the growth of ECs and SMCs under similar conditions, and to compare the effects of different doses of L-AA to determine the optimal dose for promoting maximum EC growth and inhibiting SMC growth. The ECs and SMCs treated with different drugs were characterized for their viability and proliferation, and morphology using the quantitative resazurin assay (as well as qualitative fluorescence microscopy characterization and phase contrast microscopy, respectively, for up to 7 days. Also, the phenotype of ECs was characterized using immunofluorescence microscopy. Both SIR and PAT significantly inhibited the EC growth while L-AA significantly encouraged EC growth even more than that of the controls with no drugs. Also, L-AA significantly inhibited SMC growth although the inhibitory effect was inferior to that of SIR and PAT. The L-AA dosage study demonstrated that 100 µg and 300 µg of L-AA showed maximum EC growth after 7 days when compared to other dosages (1 µg, 500 µg, and 1000 µg of L-AA and controls investigated in this study. Also, the 100 µg and 300 µg

  5. A proof-of-concept trial of protein kinase C iota inhibition with auranofin for the paclitaxel-induced acute pain syndrome.

    Science.gov (United States)

    Jatoi, Aminah; Grudem, Megan E; Dockter, Travis J; Block, Matthew S; Villasboas, Jose C; Tan, Angelina; Deering, Erin; Kasi, Pashtoon M; Mansfield, Aaron S; Botero, Juliana Perez; Okuno, Scott H; Smith, Deanne R; Fields, Alan P

    2017-03-01

    Paclitaxel causes the paclitaxel-induced acute pain (PIAP) syndrome. Based on preclinical data, we hypothesized that the protein kinase C (PKC) iota inhibitor, auranofin (a gold salt used for other pain conditions), palliates this pain. In a randomized, double-blinded manner, patients who had suffered this syndrome were assigned a one-time dose of auranofin 6 mg orally on day #2 of the chemotherapy cycle (post-paclitaxel) versus placebo. Patients completed the Brief Pain Inventory and a pain diary on days 2 through 8 and at the end of the cycle. The primary endpoint was pain scores, as calculated by area under the curve, in response to "Please rate your pain by circling the one number that best describes your pain at its worse in the last 24 hours." Thirty patients were enrolled. For the primary endpoint, mean area under the curve of 55 units (standard deviation 19) and 61 units (standard deviation 22) were observed in auranofin-treated and placebo-exposed patients, respectively (p = 0.44). On day 8 and at the end of the cycle, pain scores in auranofin-treated patients were more favorable, although differences were not statistically significant. In the dose schedule studied, auranofin did not palliate the PIAP syndrome, but delayed beneficial trends suggest further study for this indication.

  6. A phase 1/1B trial of ADI-PEG 20 plus nab-paclitaxel and gemcitabine in patients with advanced pancreatic adenocarcinoma.

    Science.gov (United States)

    Lowery, Maeve A; Yu, Kenneth H; Kelsen, David Paul; Harding, James J; Bomalaski, John S; Glassman, Danielle C; Covington, Christina M; Brenner, Robin; Hollywood, Ellen; Barba, Adalberto; Johnston, Amanda; Liu, Kay Chia-Wei; Feng, Xiaoxing; Capanu, Marinela; Abou-Alfa, Ghassan K; O'Reilly, Eileen M

    2017-12-01

    ADI-PEG 20 is a pegylated form of the arginine-depleting enzyme arginine deiminase. Normal cells synthesize arginine with the enzyme argininosuccinate synthetase (ASS1); ADI-PEG 20 selectively targets malignant cells, which lack ASS1. A single-arm, nonrandomized, open-label, phase 1/1B, standard 3 + 3 dose escalation with an expansion cohort of 9 patients at the recommended phase 2 dose (RP2D) was conducted. Patients who had metastatic pancreatic cancer, up to 1 line of prior treatment (the dose-escalation cohort) or no prior treatment (the expansion cohort), and an Eastern Cooperative Oncology Group performance status of 0 to 1 were included. Patients received both gemcitabine (1000 mg/m 2 ) and nab-paclitaxel (125 mg/m 2 ) for 3 of 4 weeks and intramuscular ADI-PEG 20 at 18 mg/m 2 weekly (cohort 1) or at 36 mg/m 2 weekly (cohort 2 and the expansion cohort).The primary endpoint was to determine the maximum tolerated dose and RP2D of ADI-PEG 20 in combination with nab-paclitaxel and gemcitabine. Eighteen patients were enrolled. No dose-limiting toxicities (DLTs) were observed in cohort 1; cohort 2 was expanded to 6 patients because of 1 DLT occurrence (a grade 3 elevation in bilirubin, aspartate aminotransferase, and alanine aminotransferase). The most frequent adverse events (AEs) of any grade were neutropenia, thrombocytopenia, leukopenia, anemia, peripheral neuropathy, and fatigue; all 18 patients experienced grade 3/4 AEs. The most frequent grade 3/4 toxicities, regardless of the relation with any drugs, included neutropenia (12 patients or 67%), leukopenia (10 patients or 56%), anemia (8 patients or 44%), and lymphopenia (6 patients or 33%). The RP2D for ADI-PEG 20 was 36 mg/m 2 weekly in combination with standard-dose gemcitabine and nab-paclitaxel. The overall response rate among patients treated at the RP2D in the first-line setting was 45.5% (5 of 11).The median progression-free survival time for these patients treated at the RP2D was 6.1 months (95

  7. Randomized Phase II trial of paclitaxel and carboplatin followed by gemcitabine switch-maintenance therapy versus gemcitabine and carboplatin followed by gemcitabine continuation-maintenance therapy in previously untreated advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Minami Seigo

    2013-01-01

    Full Text Available Abstract Background In recent years, maintenance chemotherapy is increasingly being recognized as a new treatment strategy to improve the outcome of advanced non-small cell lung cancer (NSCLC. However, the optimal maintenance strategy is still controversial. Gemcitabine is a promising candidate for single-agent maintenance therapy because of little toxicity and good tolerability. We have conducted a randomized phase II study to evaluate the validity of single-agent maintenance chemotherapy of gemcitabine and to compare continuation- and switch-maintenance. Methods Chemonaïve patients with stage IIIB/IV NSCLC were randomly assigned 1:1 to either arm A or B. Patients received paclitaxel (200 mg/m2, day 1 plus carboplatin (AUC 6 mg/mL/min, day 1 every 3 weeks in arm A, or gemcitabine (1000 mg/m2, days 1 and 8 plus carboplatin (AUC 5 mg/mL/min, day1 every 3 weeks in arm B. Non-progressive patients following 3 cycles of induction chemotherapy received maintenance gemcitabine (1000 mg/m2, days 1 and 8 every 3 weeks. (Trial registration: UMIN000008252 Results The study was stopped because of delayed accrual at interim analysis. Of the randomly assigned 50 patients, 49 except for one in arm B were evaluable. Median progression-free survival (PFS was 4.6 months for arm A vs. 3.5 months for arm B (HR = 1.03; 95% CI, 0.45–2.27; p = 0.95 and median overall survival (OS was 15.0 months for arm A vs. 14.8 months for arm B (HR = 0.79; 95% CI, 0.40–1.51; p = 0.60, showing no difference between the two arms. The response rate, disease control rate, and the transit rate to maintenance phase were 36.0% (9/25, 64.0% (16/25, and 48% (12/25 for arm A vs. 16.7% (4/24, 50.0% (12/24, and 33% (8/24 for arm B, which were also statistically similar between the two arms (p = 0.13, p = 0.32, and p = 0.30, respectively. Both induction regimens were tolerable, except that more patients experienced peripheral neuropathy in arm A. Toxicities during

  8. 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

  9. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors.

    Science.gov (United States)

    Molife, L Rhoda; Yan, Li; Vitfell-Rasmussen, Joanna; Zernhelt, Adriane M; Sullivan, Daniel M; Cassier, Philippe A; Chen, Eric; Biondo, Andrea; Tetteh, Ernestina; Siu, Lillian L; Patnaik, Amita; Papadopoulos, Kyriakos P; de Bono, Johann S; Tolcher, Anthony W; Minton, Susan

    2014-01-03

    Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies. Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK-2206 135-200 mg QW or 90-250 mg Q3W were also tested. MTD of MK-2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drug-related toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, NSCLC, and cervical cancers. Six patients had stable disease ≥6 months. MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity.

  10. A prospective randomized study of gemcitabine with doxifluridine versus paclitaxel with doxifluridine in concurrent chemoradiotherapy for locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Chung, Hye Won; Bang, Seung Min; Park, Seung Woo; Chung, Jae Bock; Kang, Jin Kyung; Kim, Ju Won; Seong, Jin Sil; Lee, Woo Jung; Song, Si Young

    2004-01-01

    Purpose: The objective of this study was to compare the efficacy and toxicity of gemcitabine-based concurrent chemoradiotherapy (CCRT) with paclitaxel-based CCRT in patients with locally advanced pancreatic cancer. Methods and materials: A total of 48 patients who had received no prior therapy were enrolled. The patients were treated with 4500 cGy radiation in 25 fractions over 5 weeks concomitant with gemcitabine 1000 mg/m 2 /week/intravenously (IV) and doxifluridine 600 mg/m 2 /day/by mouth (PO), or paclitaxel 50 mg/m 2 /week/IV and doxifluridine 600 mg/m 2 /day/PO. After a 4-week rest, the responses were evaluated and maintenance therapies (operation or chemotherapy) (gemcitabine 1000 mg/m 2 /week/IV and doxifluridine 600 mg/m 2 /day/PO) were conducted. Results: The median survival was 12 months in the gemcitabine group vs. 14 months in the paclitaxel group. The response rate was 13.6% vs. 25%, and the median time to progression was 12 months vs. 12.5 months, respectively. The positive rate of the clinical benefit response was 59.1% vs. 41.7%, respectively. Toxicities were acceptable in both groups. Conclusion: In this trial, we demonstrated that the gemcitabine-based CCRT and the paclitaxel-based CCRT in combination of doxifluridine are clearly acceptable treatment strategy, and appear more effective than the 5 fluorouracil-based CCRT for locally advanced pancreatic cancer with comparable tolerability. Furthermore, the paclitaxel-based CCRT showed similar efficacy and toxicities to the gemcitabine-based treatment when it was combined with 5-fluorouracil

  11. A phase II trial of Cremorphor EL-free paclitaxel (Genexol-PM) and gemcitabine in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Ahn, Hee Kyung; Jung, Minkyu; Sym, Sun Jin; Shin, Dong Bok; Kang, Shin Myung; Kyung, Sun Young; Park, Jeong-Woong; Jeong, Sung Hwan; Cho, Eun Kyung

    2014-08-01

    Genexol-PM is a Cremorphor EL (CrEL)-free polymeric micelle formulation of paclitaxel that allows higher-dose administration with less hypersensitivity. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients as a first-line treatment. This is a prospective, single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on day 1 and day 8 of a 3-week cycle. Six cycles of chemotherapy were planned unless there was disease progression. The primary endpoint was overall response rate. Forty-three patients received the study drugs with a median of 4 cycles per patient (range 1-6). The overall response rate was 46.5%. The median progression-free survival was 4.0 months (95% CI 2.0-6.0 months), and median overall survival was 14.8 months (95% CI 9.1-20.5 months). The most common toxicities were anemia (n = 29, 67%), asthenia (n = 17, 40%), myalgia (n = 16, 37%), peripheral neuropathy (n = 15, 35 %), and diarrhea (n = 12, 30%). The most common grade 3/4 adverse events were neutropenia (n = 7, 16%) and pneumonia (n = 5, 12%). Two patients died of pneumonia and dyspnea. CrEL-free paclitaxel in combination with gemcitabine demonstrated favorable antitumor activity with little emetogenicities in non-small cell lung cancer patients. However, frequent grade 3/4 toxicities were observed, and safety should be evaluated thoroughly in future studies.

  12. Inhibition of the Receptor Tyrosine Kinase AXL Restores Paclitaxel Chemosensitivity in Uterine Serous Cancer.

    Science.gov (United States)

    Palisoul, Marguerite L; Quinn, Jeanne M; Schepers, Emily; Hagemann, Ian S; Guo, Lei; Reger, Kelsey; Hagemann, Andrea R; McCourt, Carolyn K; Thaker, Premal H; Powell, Matthew A; Mutch, David G; Fuh, Katherine C

    2017-12-01

    Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL in vitro and in vivo We used short hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in vitro in the presence or absence of AXL. We also examined the role of the epithelial-mesenchymal transition (EMT) in AXL-mediated paclitaxel resistance. Finally, we treated USC xenografts with paclitaxel, BGB324, or paclitaxel plus BGB324 and monitored tumor burden. AXL expression was higher in chemoresistant USC patient tumors and cell lines than in chemosensitive tumors and cell lines. Knockdown or inhibition of AXL increased sensitivity of USC cell lines to paclitaxel in vitro and increased cellular accumulation of paclitaxel. AXL promoted chemoresistance even in cells that underwent the EMT in vitro Finally, in vivo studies of combination treatment with BGB324 and paclitaxel showed a greater than 51% decrease in tumor volume after 2 weeks of treatment when compared with no treatment or single-agent treatments ( P USC. Mol Cancer Ther; 16(12); 2881-91. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane®) on three treatment schedules in patients with solid tumors

    Science.gov (United States)

    Stinchcombe, Thomas E.; Socinski, Mark A.; Walko, Christine M.; O’Neil, Bert H.; Collichio, Frances A.; Ivanova, Anastasia; Mu, Hua; Hawkins, Michael J.; Goldberg, Richard M.; Lindley, Celeste; Dees, E Claire

    2010-01-01

    Purpose Albumin-bound paclitaxel, ABI-007 (Abraxane ®), has a different toxicity profile than solvent-based paclitaxel, including a lower rate of severe neutropenia. The combination of ABI-007 and carboplatin may have significant activity in a variety of tumor types including non-small and small cell lung cancer, ovarian cancer, and breast cancer. The purpose of this study was to determine the maximum tolerated dose (MTD) of ABI-007, on three different schedules in combination with carboplatin. Methods Forty-one patients with solid tumors were enrolled, and received ABI-007 in combination with carboplatin AUC of 6 on day 1. Group A received ABI-007 at doses ranging from 220 to 340 mg/m2 on day 1 every 21 days; group B received ABI-007 at 100 or 125 mg/m2 on days 1, 8, and 15 every 28 days; and group C received ABI-007 125 or 150 mg/m2 on days 1 and 8 every 21 days. Dose-limiting toxicities were assessed after the first cycle. Doses were escalated in cohorts of three to six patients. Fifteen patients participated in a pharmacokinetic study investigating the effects of the sequence of infusion. ABI-007 was infused first followed by carboplatin in cycle 1, and vice versa in cycle 2. Results The MTD of ABI-007 in combination with carboplatin was 300, 100, and 125 mg/m2 in groups A, B, and C, respectively. Myelosuppression was the primary dose limiting toxicity. No unexpected or new toxicities were reported. Sequence of infusion did not affect either the pharmacokinetics of ABI-007 or the degree of neutropenia. Responses were seen in melanoma, lung, bladder, esophageal, pancreatic, breast cancer, and cancer of unknown primary. Conclusions The recommended dose for phase II studies of ABI-007 in combination with carboplatin (AUC of 6) is 300, 100, 125 mg/m2 for the schedules A, B, and C, respectively. The combination of ABI-007 and carboplatin is well tolerated and active in this heavily pretreated patient population. PMID:17285317

  14. The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients.

    Science.gov (United States)

    Malingré, M M; Schellens, J H; Van Tellingen, O; Ouwehand, M; Bardelmeijer, H A; Rosing, H; Koopman, F J; Schot, M E; Ten Bokkel Huinink, W W; Beijnen, J H

    2001-11-16

    The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one week apart oral paclitaxel 60 mg m(-2) dissolved in polysorbate 80 or Cremophor EL. For 3 patients the amount of Cremophor EL was 5 ml m(-2), for the other three 15 ml m(-2). Prior to paclitaxel administration patients received 15 mg kg(-1) oral cyclosporin A to enhance the oral absorption of the drug. Paclitaxel formulated in polysorbate 80 resulted in a significant increase in the maximal concentration (C(max)) and area under the concentration-time curve (AUC) of paclitaxel in comparison with the Cremophor EL formulations (P = 0.046 for both parameters). When formulated in Cremophor EL 15 ml m(-2), paclitaxel C(max) and AUC values were 0.10 +/- 0.06 microM and 1.29 +/- 0.99 microM h(-1), respectively, whereas these values were 0.31 +/- 0.06 microM and 2.61 +/- 1.54 microM h(-1), respectively, when formulated in polysorbate 80. Faecal data revealed a decrease in excretion of unchanged paclitaxel for the polysorbate 80 formulation compared to the Cremophor EL formulations. The amount of paclitaxel excreted in faeces was significantly correlated with the amount of Cremophor EL excreted in faeces (P = 0.019). When formulated in Cremophor EL 15 ml m(-2), paclitaxel excretion in faeces was 38.8 +/- 13.0% of the administered dose, whereas this value was 18.3 +/-15.5% for the polysorbate 80 formulation. The results show that the co-solvent Cremophor EL is an important factor limiting the absorption of orally administered paclitaxel from the intestinal lumen. They highlight the need for designing a better drug formulation in order to increase the usefulness of the oral route of paclitaxel

  15. Cold therapy to prevent paclitaxel-induced peripheral neuropathy.

    Science.gov (United States)

    Griffiths, Claire; Kwon, Nancy; Beaumont, Jennifer L; Paice, Judith A

    2018-04-21

    This case-control study was designed to assess the efficacy of cryotherapy to prevent paclitaxel-induced painful peripheral neuropathy in women with breast cancer. Participants served as their own paired control, with randomization of the cooled glove/sock to either the dominant or the non-dominant hand/foot, worn for 15 min prior to, during, and 15 min after completion of the paclitaxel infusion. Outcome measures included the Neuropathic Pain Symptom Inventory, the Brief Pain Inventory, and quantitative sensory testing. Data were measured at each of six time points-baseline, post-treatment (approximately 2 weeks after the last paclitaxel infusion), and at the first, fifth, ninth, and final weekly paclitaxel treatments. Of 29 randomized participants, 20 (69%) received at least one cryotherapy treatment, and 11 (38%) received all four cryotherapy treatments. Ten (34%) participants could not tolerate the cryotherapy, and six (21%) declined further participation at some point during the trial. Only seven participants (24%) were available for the final post-chemotherapy QST and questionnaires. There were no significant differences in measures of neuropathy or pain between treated and untreated hands or feet. Strategies to prevent painful peripheral neuropathy are urgently needed. In this current trial, dropout due to discomfort precluded adequate power to fully understand the potential benefits of cryotherapy. Much more research is needed to discover safe and effective preventive strategies that can be easily implemented within busy infusion centers.

  16. A Liposomal Formulation Able to Incorporate a High Content of Paclitaxel and Exert Promising Anticancer Effect

    Directory of Open Access Journals (Sweden)

    Pei Kan

    2011-01-01

    Full Text Available A liposome formulation for paclitaxel was developed in this study. The liposomes, composed of naturally unsaturated and hydrogenated phosphatidylcholines, with significant phase transition temperature difference, were prepared and characterized. The liposomes exhibited a high content of paclitaxel, which was incorporated within the segregated microdomains coexisting on phospholipid bilayer of liposomes. As much as 15% paclitaxel to phospholipid molar ratio were attained without precipitates observed during preparation. In addition, the liposomes remained stable in liquid form at 4∘C for at least 6 months. The special composition of liposomal membrane which could reduce paclitaxel aggregation could account for such a capacity and stability. The cytotoxicity of prepared paclitaxel liposomes on the colon cancer C-26 cell culture was comparable to Taxol. Acute toxicity test revealed that LD50 for intravenous bolus injection in mice exceeded by 40 mg/kg. In antitumor efficacy study, the prepared liposomal paclitaxel demonstrated the increase in the efficacy against human cancer in animal model. Taken together, the novel formulated liposomes can incorporate high content of paclitaxel, remaining stable for long-term storage. These animal data also demonstrate that the liposomal paclitaxel is promising for further clinical use.

  17. A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

    Directory of Open Access Journals (Sweden)

    Wehrenberg Scott

    2010-01-01

    Full Text Available Abstract Background Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials. Methods/Design The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1, single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express2 paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to Discussion The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at http://www.clinicaltrials.gov, identification numbers NCT00484315 and NCT00489541.

  18. A Prospective Comparative Study of the Toxicity Profile of 5-Flurouracil, Adriamycin, Cyclophosphamide Regime VS Adriamycin, Paclitaxel Regime in Patients with Locally Advanced Breast Carcinoma

    Science.gov (United States)

    Pillai, Pradeep Sadasivan; Jayakumar, Krishnan Nair Lalithamma

    2015-01-01

    Introduction A 5-flurouracil, Adriamycin, Cyclophosphamide (FAC) and Adriamycin, Paclitaxel (AT) are two popular chemotherapeutic regimens for treatment of breast carcinoma. The most time tested and popular regimen is FAC. It is extensively studied for efficacy and toxicity. But data regarding toxicity profile and efficacy of AT regimen is sparse. Aim To study the toxicity profile, severity of toxicities and clinical response rate of FAC and AT regimens in patients with locally advanced breast carcinoma. Materials and Methods A prospective observational study with 50 patients in each treatment arm. Study duration was 12 months from November 2012 to October 2013. Consecutive patients with locally advanced breast carcinoma receiving treatment with either FAC or AT regimen, satisfying inclusion criteria were enrolled into the study after getting informed written consent. Prior to initiation of treatment detailed medical history was taken from all patients. General clinical examination, examination of organ systems and local examination of breast lump were done. After each cycle of chemotherapy and after completion of treatment patients were interviewed and examined for clinical response and toxicities. Toxicities were graded with WHO toxicity grading criteria. All data were entered in a structured proforma. At least 50% reduction in tumour size was taken as adequate clinical response. Statistical Analysis Data was analysed using Chi-square test with help of Excel 2007 and SPSS-16 statistical software. Results Different pattern of toxicities were seen with FAC and AT regimens. Anaemia, thrombocytopenia, stomatitis, hyperpigmentation, photosensitivity and diarrhoea were more common with patients receiving FAC regimen. Leucopenia, peripheral neuropathy, myalgia, arthralgia, vomiting and injection site reactions were more common in AT regimen. Both FAC and AT regimens gave 100% clinical response. Conclusion FAC and AT regimens are equally efficacious but have different

  19. Enabling Anticancer Therapeutics by Nanoparticle Carriers: The Delivery of Paclitaxel

    Directory of Open Access Journals (Sweden)

    Bing Yan

    2011-07-01

    Full Text Available Anticancer drugs, such as paclitaxel (PTX, are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to enable drug delivery due to their low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. This review takes paclitaxel as an example and compares different nanoparticle-based delivery systems for their effectiveness in cancer chemotherapy.

  20. A preliminary report on the effects of paclitaxel-impregnated stents on sheep nasal mucosa.

    Science.gov (United States)

    Herrmann, Brian W; Citardi, Martin J; Vogler, George; Gardner, Laura; Smith, Greg; Javer, Amin R; Burt, Helen M; Jackson, John; Kuhn, Frederick A

    2004-01-01

    Traditional frontal sinus stents serve only as mechanical devices. It has been proposed that stents also may serve as drug-delivery systems for the topical application of drugs that minimize postoperative scarring. Paclitaxel (Taxol), which has recognized antiscarring effects, may be incorporated via a polymeric formulation into standard rubber stents. The impact of topically applied paclitaxel on the morphology of the nasal mucosa is unknown. An adult sheep model was used for this study. A modified rubber T-tube stent (incorporating paclitaxel at varying dosages) was secured to each side of the septum in four animals (eight sides). An unmodified T-tube was placed on each side of one animal, a T-tube with the drug carrier (but no paclitaxel) was placed on each side of the second animal, and T-tubes with varying paclitaxel were placed on each side of the final two animals. After 4 weeks, animals were killed and the nasal mucosa was harvested. The nasal mucosa was sectioned and stained with hematoxylin and eosin. A pathologist then assessed the nasal mucosa for vascular congestion, glandular atrophy, chronic inflammation, mucosal metaplasia, and mucosal ulceration. No consistent histopathological differences were noted in the specimens. All specimens showed varying degrees of vascular congestion, glandular atrophy, chronic inflammation, and mucosal metaplasia; the paclitaxel-impregnated stents were not consistently associated with more severe mucosal injury. Finally, mucosal ulceration was noted to be very rare in all specimens. This preliminary report describes the impact of paclitaxel-impregnated stents on sheep nasal mucosa, which tolerated these stents very well. Because paclitaxel minimizes scarring reactions at very low concentrations, paclitaxel-impregnated stents may prove useful in clinical situations in which frontal sinus stenting is deemed necessary. Additional investigations with animal models, as well as clinical trials, may be warranted.

  1. Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

    Directory of Open Access Journals (Sweden)

    Mehmet Fidanboylu

    Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

  2. Comparative trials in registration files of cardiovascular drugs : Comparator drugs and dosing schemes.

    NARCIS (Netherlands)

    Wieringa, NF; Vos, R; de Graeff, PA

    Registration files of 13 cardiovascular drugs were analysed with respect to the number of double-blind phase-III clinical trials, the use of placebo and active comparator drugs and their dosing schemes. Half of the 146 double-blind trials used active comparator drugs. The majority of files included

  3. 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

  4. Excel-Based Tool for Pharmacokinetically Guided Dose Adjustment of Paclitaxel.

    Science.gov (United States)

    Kraff, Stefanie; Lindauer, Andreas; Joerger, Markus; Salamone, Salvatore J; Jaehde, Ulrich

    2015-12-01

    Neutropenia is a frequent and severe adverse event in patients receiving paclitaxel chemotherapy. The time above a paclitaxel threshold concentration of 0.05 μmol/L (Tc > 0.05 μmol/L) is a strong predictor for paclitaxel-associated neutropenia and has been proposed as a target pharmacokinetic (PK) parameter for paclitaxel therapeutic drug monitoring and dose adaptation. Up to now, individual Tc > 0.05 μmol/L values are estimated based on a published PK model of paclitaxel by using the software NONMEM. Because many clinicians are not familiar with the use of NONMEM, an Excel-based dosing tool was developed to allow calculation of paclitaxel Tc > 0.05 μmol/L and give clinicians an easy-to-use tool. Population PK parameters of paclitaxel were taken from a published PK model. An Alglib VBA code was implemented in Excel 2007 to compute differential equations for the paclitaxel PK model. Maximum a posteriori Bayesian estimates of the PK parameters were determined with the Excel Solver using individual drug concentrations. Concentrations from 250 patients were simulated receiving 1 cycle of paclitaxel chemotherapy. Predictions of paclitaxel Tc > 0.05 μmol/L as calculated by the Excel tool were compared with NONMEM, whereby maximum a posteriori Bayesian estimates were obtained using the POSTHOC function. There was a good concordance and comparable predictive performance between Excel and NONMEM regarding predicted paclitaxel plasma concentrations and Tc > 0.05 μmol/L values. Tc > 0.05 μmol/L had a maximum bias of 3% and an error on precision of 0.05 μmol/L values between both programs was 1%. The Excel-based tool can estimate the time above a paclitaxel threshold concentration of 0.05 μmol/L with acceptable accuracy and precision. The presented Excel tool allows reliable calculation of paclitaxel Tc > 0.05 μmol/L and thus allows target concentration intervention to improve the benefit-risk ratio of the drug. The easy use facilitates therapeutic drug monitoring in

  5. The battle of "nano" paclitaxel

    NARCIS (Netherlands)

    Sofias, Alexandros Marios; Dunne, Michael; Storm, Gert; Allen, Christine

    2017-01-01

    Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best-selling cancer drug of all time with annual

  6. Dose-dense paclitaxel with carboplatin for advanced ovarian cancer: a feasible treatment alternative.

    Science.gov (United States)

    Glaze, Sarah; Teitelbaum, Lisa; Chu, Pamela; Ghatage, Prafull; Nation, Jill; Nelson, Gregg

    2013-01-01

    Epithelial ovarian cancer is the leading cause of death from gynaecologic cancers in the Western world. If possible, initial cytoreductive surgery is the treatment of choice, followed by adjuvant chemotherapy, usually with a platinum/taxane combination. Increased survival has been recently reported in women who were given adjuvant chemotherapy weekly rather than at three-week intervals, which has been the standard. At our centre, we have been treating patients with advanced ovarian cancer with a dose-dense protocol since March 2010. Treatment is given in an outpatient setting on days 1, 8, and 15 of a 21-day cycle for six cycles. Carboplatin for an AUC of 5 mg/mL/min and paclitaxel 80mg/m² are given on day 1, followed by paclitaxel 80mg/m² on days 8 and 15. Our objective was to determine whether this protocol is a feasible alternative treatment in our population and whether or not the toxicity profile is acceptable. We performed a chart review of 46 patients undergoing treatment with dose-dense chemotherapy for advanced ovarian cancer. Demographic information, patient characteristics, adverse events, and treatment endpoints were recorded. Sixty-one percent of women completed the six-cycle protocol as planned with minimal interruption, which is comparable to the only previously reported trial using this regimen. The most common side effects of treatment were fatigue, neuropathy, and neutropenia. Supplementation with regular magnesium and granulocyte colony-stimulating factor reduced delays. Dose-dense paclitaxel with carboplatin chemotherapy for the treatment of advanced ovarian cancer shows promise in terms of progression-free and overall survival. We have shown this protocol to be practical and feasible in our population.

  7. A randomised comparison of an everolimus-eluting coronary stent with a paclitaxel-eluting coronary stent:the SPIRIT II trial

    NARCIS (Netherlands)

    Serruys, Patrick W.; Ruygrok, Peter; Neuzner, Jörg; Piek, Jan J.; Seth, Ashok; Schofer, Joachim J.; Richardt, Gert; Wiemer, Marcus; Carrié, Didier; Thuesen, Leif; Boone, Els; Miquel-Herbert, Karine; Daemen, Joost

    2006-01-01

    Background: Everolimus has been successfully tested in humans using both an erodable and a durable polymer in small previous studies.Methods: This single blind multi-centre non-inferiority randomised (3:1) controlled trial evaluated the safety and performance of the XIENCE V Everolimus Eluting

  8. Efficacy and toxicological studies of cremophor EL free alternative paclitaxel formulation.

    Science.gov (United States)

    Utreja, Puneet; Jain, Subheet; Yadav, Subodh; Khandhuja, K L; Tiwary, A K

    2011-11-01

    In the present study, Cremophor EL free paclitaxel elastic liposomal formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate was developed and optimized. The toxicological profile, antitumor efficacy and hemolytic toxicity of paclitaxel elastic liposomal formulation in comparison to Cremophor EL based marketed formulation were evaluated. Paclitaxel elastic liposomal formulations were prepared and characterized in vitro, ex-vivo and in vivo. Single dose toxicity study of paclitaxel elastic liposomal and marketed formulation was carried out in dose range of 10, 20, 40, 80, 120, 160 and 200 mg/kg. Cytotoxicity of developed formulation was evaluated using small cell lung cancer cell line (A549). Antitumor activity of developed formulation was compared with the marketed formulation using Cytoselect™ 96-well cell transformation assay. In vivo administration of paclitaxel elastic liposomal formulation into mice showed 6 fold increase in Maximum Tolerated Dose (MTD) in comparison to the marketed formulation. Similarly, LD50 (141.6 mg/kg) was also found to increase significantly than the marketed formulation (16.7 mg/kg). Result of antitumor assay revealed a high reduction of tumor density with paclitaxel elastic liposomal formulation. Reduction in hemolytic toxicity was also observed with paclitaxel elastic liposomal formulation in comparison to the marketed formulation. The carrier based approach for paclitaxel delivery demonstrated significant reduction in toxicity as compared to the Cremophor EL based marketed formulation following intra-peritoneal administration in mice model. The reduced toxicity and enhanced anti-cancer activity of elastic liposomal formulation strongly indicate its potential for safe and effective delivery of paclitaxel.

  9. Development of New Lipid-Based Paclitaxel Nanoparticles Using Sequential Simplex Optimization

    Science.gov (United States)

    Dong, Xiaowei; Mattingly, Cynthia A.; Tseng, Michael; Cho, Moo; Adams, Val R.; Mumper, Russell J.

    2008-01-01

    The objective of these studies was to develop Cremophor-free lipid-based paclitaxel (PX) nanoparticle formulations prepared from warm microemulsion precursors. To identify and optimize new nanoparticles, experimental design was performed combining Taguchi array and sequential simplex optimization. The combination of Taguchi array and sequential simplex optimization efficiently directed the design of paclitaxel nanoparticles. Two optimized paclitaxel nanoparticles (NPs) were obtained: G78 NPs composed of glyceryl tridodecanoate (GT) and polyoxyethylene 20-stearyl ether (Brij 78), and BTM NPs composed of Miglyol 812, Brij 78 and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both nanoparticles successfully entrapped paclitaxel at a final concentration of 150 μg/ml (over 6% drug loading) with particle sizes less than 200 nm and over 85% of entrapment efficiency. These novel paclitaxel nanoparticles were stable at 4°C over three months and in PBS at 37°C over 102 hours as measured by physical stability. Release of paclitaxel was slow and sustained without initial burst release. Cytotoxicity studies in MDA-MB-231 cancer cells showed that both nanoparticles have similar anticancer activities compared to Taxol®. Interestingly, PX BTM nanocapsules could be lyophilized without cryoprotectants. The lyophilized powder comprised only of PX BTM NPs in water could be rapidly rehydrated with complete retention of original physicochemical properties, in-vitro release properties, and cytotoxicity profile. Sequential Simplex Optimization has been utilized to identify promising new lipid-based paclitaxel nanoparticles having useful attributes. PMID:19111929

  10. Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.

    Science.gov (United States)

    Unger, E C; McCreery, T P; Sweitzer, R H; Caldwell, V E; Wu, Y

    1998-12-01

    Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

  11. Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

    Directory of Open Access Journals (Sweden)

    Wang YL

    2011-07-01

    Full Text Available Yonglu Wang1,4, Xueming Li1,2*, Liyao Wang3, Yuanlong Xu1, Xiaodan Cheng1, Ping Wei41College of Pharmacy, Nanjing University of Technology, Nanjing; 2State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing University of Technology, Nanjing; 3College of Life Science, Anhui Agricultural University, Hefei; 4College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing, People’s Republic of China *These authors contributed equally to this work.Abstract: Paclitaxel is a diterpenoid isolated from Taxus brevifolia. It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor® EL (BASF, Ludwigshafen, Germany, which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was formulated as a nanosuspension by high-pressure homogenization. The nanosuspension was lyophilized to obtain the dry paclitaxel nanoparticles (average size, 214.4 ± 15.03 nm, which enhanced both the physical and chemical stability of paclitaxel nanoparticles. Paclitaxel dissolution was also enhanced by the nanosuspension. Differential scanning calorimetry showed that the crystallinity of paclitaxel was preserved during the high-pressure homogenization process. The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection. In rat plasma, paclitaxel nanosuspension exhibited a significantly (P < 0.01 reduced area under the concentration curve (AUC0–∞ (20.343 ± 9.119 µg · h · mL−1 vs 5.196 ± 1.426 µg · h · mL−1, greater clearance (2.050 ± 0.616 L · kg−1 · h−1 vs 0.556 ± 0.190 L · kg−1 · h−1, and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours compared with the paclitaxel solution. In contrast, the paclitaxel nanosuspension resulted in a

  12. Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Randomized Phase 2 Trial of Neoadjuvant Preoperative Paclitaxel/Cisplatin/Radiation Therapy (RT) or Irinotecan/Cisplatin/RT in Esophageal Adenocarcinoma: Long-Term Outcome and Implications for Trial Design

    Energy Technology Data Exchange (ETDEWEB)

    Kleinberg, Lawrence R., E-mail: kleinla@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Harvard T.H. Chan School of Public Health, Boston, Massachusetts (United States); Forastiere, Arlene A. [Department of Oncology, Johns Hopkins University, Baltimore, Maryland (United States); Keller, Steven M. [Department of Cardiovascular and Thoracic Surgery, Montefiore Medical Center, Bronx, NY (United States); Mitchel, Edith P. [Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Anne, Pramila Rani [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Benson, Al B. [Department of Medicine-Hematology/Oncology, Lurie Cancer Center, Northwestern University, Chicago, Illinois (United States)

    2016-03-15

    Purpose: Toxicity, pathologic complete response, and long-term outcomes are reported for the neoadjuvant therapies assessed in a randomized phase 2 Eastern Cooperative Oncology Group and American College of Radiology Imaging Network trial for operable esophageal adenocarcinoma, staged as II-IVa by endoscopy/ultrasonography (EUS). Methods and Materials: A total of 86 eligible patients began treatment. For arm A, preoperative chemotherapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 50 mg/m{sup 2}, on day 1, 8, 22, 29 during 45 Gy radiation therapy (RT), 1.8 Gy per day over 5 weeks. Adjuvant therapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 65 mg/m{sup 2} day 1, 8 every 21 days for 3 cycles. Arm B therapy was cisplatin, 30 mg/m{sup 2}, and paclitaxel, 50 mg/m{sup 2}, day 1, 8, 15, 22, 29 with RT, followed by adjuvant cisplatin, 75 mg/m{sup 2}, and paclitaxel, 175 mg/m{sup 2}, day 1 every 21 days for 3 cycles. Stratification included EUS stage and performance status. Results: In arm A, median overall survival was 35 months, and 5-, 6-, and 7-year survival rates were 46%, 39%, and 35%, respectively, whereas for arm B, they were 21 months and 27%, 27%, and 23%, respectively. Median progression- or recurrence-free survival (PFS) was 39.8 months with a 3-year PFS of 50% for arm A and 12.4 months (P=.046) with 3-year PFS of 28% for arm B. Eighty percent of the observed incidents of progression occurred within 19 months. Survival did not differ significantly by EUS and performance status strata. Conclusions: Long-term survival was similar for both arms and did not appear superior to results achieved with other standard regimens.

  13. Clinical Trial Of Glimepiride Compared With Glibenclamide For ...

    African Journals Online (AJOL)

    Objective: The study was undertaken to compare the efficacy and safety of Glimepiride against Glibenclamide in the management of patients with type 2 DM in Jos, Nigeria. Study design: An open, randomised controlled trial. Setting: Diabetes Clinic of the Jos University Teaching Hospital, Jos, Nigeria. Subjects: Seventy four ...

  14. A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety ...

    African Journals Online (AJOL)

    A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety and Cost Effectiveness of Lornoxicam with Diclofenac Sodium in Patients of Osteoarthritis Knee. ... All patients were assessed with visual analogue scale and 100 meter walking test before starting of therapy, at 15 days and at 1, 2 and 3 months of therapy.

  15. Randomized phase III study comparing paclitaxel/cisplatin/ gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC intergroup study 30987

    NARCIS (Netherlands)

    J. Bellmunt (Joaquim); H. von der Maase (Hans); G.M. Mead (Graham); I. Skoneczna (I.); M. de Santis (Maria); G. Daugaard (Gedske); J. Boehle; C. Chevreau (Christine); L. Paz-Ares (Luis); L.R. Laufman (Leslie); E. Winquist (Eric); R. Raghavan (Raghu); S. Marreaud (Sandrine); S. Collette (Sandra); R. Sylvester (Richard); R. de Wit (Ronald)

    2012-01-01

    textabstractPurpose: The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival.

  16. Cytotoxicity and cell-cycle effects of paclitaxel when used as a single agent and in combination with ionizing radiation

    International Nuclear Information System (INIS)

    Gupta, Nalin; Hu, Lily J.; Deen, Dennis F.

    1997-01-01

    Purpose: This study aimed to determine the extent of paclitaxel-induced cytotoxicity and cell-cycle perturbations when used alone and in combination with radiation in human glioma cells. Methods and Materials: The effect of paclitaxel alone on three human glioma cells lines--SF-126, U-87 MG, and U-251 MG--was assessed after 24, 48, 72, or 96 h treatment. For experiments in combination with radiation, cells were exposed to either a long (48-h) or short (8-h) duration of paclitaxel treatment prior to irradiation. Cell survival was determined by clonogenic assay. Cell cycle perturbations were assessed by using flow cytometry to measure the proportion of cells in G 1 , S, and G 2 /M phases. Results: When cells were treated with paclitaxel alone for ≥24 h, cytotoxicity increased up to a threshold dose, after which it plateaued. When treatment duration was ≤24 h, cytotoxicity was appreciably greater in U-251 MG cells than in SF-126 and U-87 MG cells. After 24 h of paclitaxel treatment, cells in plateau phase growth had increased survival compared to cells in log phase growth. In contrast, after 8 h paclitaxel treatment, mitotic cells had reduced survival compared to cells from an asynchronous population. Cell-cycle perturbations were consistent with the presence of a mitotic block after paclitaxel treatment, although changes in other cell-cycle phase fractions varied among cell lines. For experiments in combination with radiation, cytotoxicity was increased when cells were irradiated after 48 h of paclitaxel treatment but not after 8 h of treatment. Conclusion: The duration of paclitaxel treatment and the location of cells in the cell cycle modify the degree of radiation cytotoxicity. The mechanisms of paclitaxel cytotoxicity are likely to be multifactorial because varying effects are seen in different cell lines. Furthermore, it is clear that simply increasing the number of cells in G 2 /M is insufficient in itself to increase the response of cells to radiation

  17. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Lekha Saha

    2012-01-01

    Full Text Available Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel + 0.9% NaCl, Gr III: paclitaxel + lercanidipine 0.5 μg/kg, Gr IV: paclitaxel + lercanidipine 1 μg/kg, and Gr V: paclitaxel + lercanidipine 2.5 μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i.p. injection of 1 mg/kg of paclitaxel on four alternate days (0, 2, 4, and 6. The tail flick and cold allodynia methods were used for assessing the pain threshold, and the assessments were done on days 0 (before first dose of paclitaxel and on days 7, 14, 21, and 28. Results. There was a significant decrease (P<0.001 in the tail flick and cold allodynia latency in the paclitaxel-alone group from day 14 onward when compared with day 0. In the lercanidipine groups, the decrease in the tail flick and cold allodynia latency was not observed in 1.0 and 2.5 μg/kg groups and it was statistically significant (P<0.01 when compared with paclitaxel-alone group.

  18. Feasibility Study of EndoTAG-1, a Tumor Endothelial Targeting Agent, in Combination with Paclitaxel followed by FEC as Induction Therapy in HER2-Negative Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Michail Ignatiadis

    Full Text Available EndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC in combination with paclitaxel.HER2-negative BC patients candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weekly EndoTAG-1 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 every 3 weeks followed by surgery. Primary endpoint was percent (% reduction in Magnetic Resonance Imaging (MRI estimated Gadolinium (Gd enhancing tumor volume at the end of EndoTAG-1 plus paclitaxel administration as compared to baseline. Safety, pathological complete response (pCR defined as no residual tumor in breast and axillary nodes at surgery and correlation between % reduction in MRI estimated tumor volume and pCR were also evaluated.Fifteen out of 20 scheduled patients were included: Six patients with estrogen receptor (ER-negative/HER2-negative and 9 with ER-positive/HER2-negative BC. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to EndoTAG-1 were observed during the 1st, 2nd, 3rd and 6th weekly infusion in 4 patients, respectively, and required permanent discontinuation of the EndoTAG-1. Moreover, two additional patients stopped EndoTAG-1 plus paclitaxel after 8 and 9 weeks due to clinical disease progression. Two patients had grade 3 increases in transaminases and 1 patient grade 4 neutropenia. pCR was achieved in 5 of the 6 ER-/HER2- and in none of the 9 ER+/HER2- BC patients. The mean % reduction in MRI estimated tumor volume at the end of EndoTAG-1 plus paclitaxel treatment was 81% (95% CI, 66% to 96%, p<0.001 for the 15 patients that underwent surgery; 96% for patients with pCR and 73% for patients with no pCR (p = 0.04.The EndoTAG-1 and paclitaxel combination showed promising preliminary activity as preoperative treatment, especially in ER-/HER2

  19. Decision on performing interim analysis for comparative clinical trials.

    Science.gov (United States)

    Pak, Kyongsun; Jacobus, Susanna; Uno, Hajime

    2017-09-01

    In randomized-controlled trials, interim analyses are often planned for possible early trial termination to claim superiority or futility of a new therapy. While unblinding is necessary to conduct the formal interim analysis in blinded studies, blinded data also have information about the potential treatment difference between the groups. We developed a blinded data monitoring tool that enables investigators to predict whether they observe such an unblinded interim analysis results that supports early termination of the trial. Investigators may skip some of the planned interim analyses if an early termination is unlikely. We specifically focused on blinded, randomized-controlled studies to compare binary endpoints of a new treatment with a control. Assuming one interim analysis is planned for early termination for superiority or futility, we conducted extensive simulation studies to assess the impact of the implementation of our tool on the size, power, expected number of interim analyses, and bias in the treatment effect. The numerical study showed the proposed monitoring tool does not affect size or power, but dramatically reduces the expected number of interim analyses when the effect of the treatment difference is small. The tool serves as a useful reference when interpreting the summary of the blinded data throughout the course of the trial, without losing integrity of the study. This tool could potentially save the study resources and budget by avoiding unnecessary interim analyses.

  20. Cost Analyses in the US and Japan: A Cross-Country Comparative Analysis Applied to the PRONOUNCE Trial in Non-Squamous Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Hess, Lisa M; Rajan, Narayan; Winfree, Katherine; Davey, Peter; Ball, Mark; Knox, Hediyyih; Graham, Christopher

    2015-12-01

    Health technology assessment is not required for regulatory submission or approval in either the United States (US) or Japan. This study was designed as a cross-country evaluation of cost analyses conducted in the US and Japan based on the PRONOUNCE phase III lung cancer trial, which compared pemetrexed plus carboplatin followed by pemetrexed (PemC) versus paclitaxel plus carboplatin plus bevacizumab followed by bevacizumab (PCB). Two cost analyses were conducted in accordance with International Society For Pharmacoeconomics and Outcomes Research good research practice standards. Costs were obtained based on local pricing structures; outcomes were considered equivalent based on the PRONOUNCE trial results. Other inputs were included from the trial data (e.g., toxicity rates) or from local practice sources (e.g., toxicity management). The models were compared across key input and transferability factors. Despite differences in local input data, both models demonstrated a similar direction, with the cost of PemC being consistently lower than the cost of PCB. The variation in individual input parameters did affect some of the specific categories, such as toxicity, and impacted sensitivity analyses, with the cost differential between comparators being greater in Japan than in the US. When economic models are based on clinical trial data, many inputs and outcomes are held consistent. The alterable inputs were not in and of themselves large enough to significantly impact the results between countries, which were directionally consistent with greater variation seen in sensitivity analyses. The factors that vary across jurisdictions, even when minor, can have an impact on trial-based economic analyses. Eli Lilly and Company.

  1. Stent thrombosis: insights on outcomes, predictors and impact of dual antiplatelet therapy interruption from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials.

    Science.gov (United States)

    Kedhi, Elvin; Stone, Gregg W; Kereiakes, Dean J; Serruys, Patrick W; Parise, Helen; Fahy, Martin; Simonton, Charles A; Sudhir, Krishnankutty; Sood, Poornima; Smits, Pieter C

    2012-09-01

    Recent studies have suggested that EES may reduce ST compared to PES, but no individual trial has been adequately powered for this endpoint. The incidence of stent thrombosis, as well as the impact of dual antiplatelet therapy (DAPT) discontinuation during the first two years following everolimus-eluting stent (EES) and paclitaxel-eluting stent (PES) deployment were therefore analysed from a pooled, patient-level database derived from four randomised clinical trials. Data from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials (n=6,789 patients) were analysed. Two-year ST rates were determined using time-to-event methods and compared with the log-rank test. ST rates were also determined after DAPT discontinuation. EES compared to PES significantly reduced the two-year rates of ST (0.7% versus 2.3%, p=0.0001), including the interval rates of ST up to 30 days (0.2% versus 1.0%, p<0.0001), between 31 days and one year (0.2% versus 0.6%, p=0.02), and after one year (0.3% versus 0.8%, p=0.001). EES also reduced the two-year composite rate of cardiac death or MI (4.0% versus 6.6%, p=0.0001). Increased rates of ST after DAPT discontinuation beyond six months were observed in the PES cohort, but not in the EES cohort. In this large pooled analysis from four randomised trials, treatment with EES compared to PES significantly reduced the rates of ST through two years of follow-up, with a concomitant reduction in cardiac death or MI. DAPT discontinuation beyond six months may be safe with EES.

  2. A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

    International Nuclear Information System (INIS)

    Cho, Hanbyoul; Nam, Byung-Ho; Kim, Seok Mo; Cho, Chi-Heum; Kim, Byoung Gie; Ryu, Hee-Sug; Kang, Soon Beom; Kim, Jae-Hoon

    2014-01-01

    Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m 2 was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study

  3. A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Hanbyoul [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, Byung-Ho [Cancer Biostatistics Branch, Research Institute for National Cancer Control and Evaluation, National Cancer Center, Goyang (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University School of Medicine, Gwangju (Korea, Republic of); Cho, Chi-Heum [Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu (Korea, Republic of); Kim, Byoung Gie [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ryu, Hee-Sug [Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon (Korea, Republic of); Kang, Soon Beom [Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Kim, Jae-Hoon, E-mail: jaehoonkim@yuhs.ac [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-01

    Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m{sup 2} was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.

  4. Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells

    OpenAIRE

    Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Kanterewicz, Beatriz; Balius, Trent; Belani, Chandra P.; Hershberger, Pamela A.

    2010-01-01

    We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 h of continuous drug exposure. Vorinostat (1 µM) inhibited growth by: 17±7% in A549, 28±6% in 128-88T, 39±8% in Calu1, and 41±7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel le...

  5. Nab-Paclitaxel plus gemcitabine in patients with metastatic pancreatic adenocarcinoma: experience of use

    Directory of Open Access Journals (Sweden)

    Elena Ferris Villanueva

    2015-02-01

    Full Text Available Objective: To evaluate the results obtained with the combined use of nab-paclitaxel and gemcitabine in the treatment of patients with metastatic pancreatic adenocarcinoma. Materials and methods: Retrospective observational study. Patients treated with nab-paclitaxel and gemcitabine between January of 2013 and January of 2014 were selected. Demographical and clinical data were gathered. Results: 15 patients (mean age 59,4 ± 10,3 years were included. All patients received the combination of nab-paclitaxel and gemcitabine in first-line metastatic disease. Nine received adjuvant treatment before the disease was metastatic. The median progression-free survival rate with combined nab-paclitaxel and gemcitabine was 5,6 months (95% CI: 4,44 - 8,03. In two patients the treatment was stopped due to toxicity. Conclusions: The treatment with nab-paclitaxel and gemcitabine in our patients resulted in progression-free survival rates similar to those published in clinical trials with good treatment tolerability

  6. The battle of "nano" paclitaxel.

    Science.gov (United States)

    Sofias, Alexandros Marios; Dunne, Michael; Storm, Gert; Allen, Christine

    2017-12-01

    Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best-selling cancer drug of all time with annual sales of 1.6 billion. In 2005, the introduction of the albumin-based formulation of PTX, known as Abraxane, ended Taxol's monopoly of the PTX market. Abraxane's ability to push the Taxol innovator and generic formulations aside attracted fierce competition amongst competitors worldwide to develop their own unique, new and improved formulation of PTX. At this time there are at least 18 companies focused on pre-clinical and/or clinical development of nano-formulations of PTX. These pharmaceutical companies are investing substantial capital to capture a share of the lucrative global PTX market. It is hoped that any formulation that dominates the market will result in tangible benefits to patients in terms of both survival and quality of life. Given all of this activity, here we address the question: Who is going to win the battle of "nano" paclitaxel? Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A randomized trial comparing treatments for varicose veins.

    Science.gov (United States)

    Brittenden, Julie; Cotton, Seonaidh C; Elders, Andrew; Ramsay, Craig R; Norrie, John; Burr, Jennifer; Campbell, Bruce; Bachoo, Paul; Chetter, Ian; Gough, Michael; Earnshaw, Jonothan; Lees, Tim; Scott, Julian; Baker, Sara A; Francis, Jill; Tassie, Emma; Scotland, Graham; Wileman, Samantha; Campbell, Marion K

    2014-09-25

    Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness and safety remain uncertain. In a randomized trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of foam, laser, and surgical treatments. Primary outcomes at 6 months were disease-specific quality of life and generic quality of life, as measured on several scales. Secondary outcomes included complications and measures of clinical success. After adjustment for baseline scores and other covariates, the mean disease-specific quality of life was slightly worse after treatment with foam than after surgery (P=0.006) but was similar in the laser and surgery groups. There were no significant differences between the surgery group and the foam or the laser group in measures of generic quality of life. The frequency of procedural complications was similar in the foam group (6%) and the surgery group (7%) but was lower in the laser group (1%) than in the surgery group (Pdisease-specific quality of life in the foam group than in the surgery group. All treatments had similar clinical efficacy, but complications were less frequent after laser treatment and ablation rates were lower after foam treatment. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN51995477.).

  8. Evaluation of In-111 DTPA-paclitaxel scintigraphy to predict response on murine tumors to paclitaxel

    International Nuclear Information System (INIS)

    Inoue, Tomio; Li, C.; Yang, D.J.

    1999-01-01

    Our goal was to determine whether scintigraphy with 111 In-DTPA-paclitaxel could predict the response to chemotherapy with paclitaxel. Ovarian carcinoma (OCA 1), mammary carcinoma (MCA-4), fibrosarcoma (FSA) and squamous cell carcinoma (SCC VII) were inoculated into the thighs of female C3Hf/Kam mice. Mice bearing 8 mm tumors were treated with paclitaxel (40 mg/kg). The growth delay, which was defined as the time in days for tumors in the treated groups to grow from 8 to 12 mm in diameter minus the time in days for tumors in the untreated control group to reach the same size, was measured to determine the effect of paclitaxel on the tumors. Sequential scintigraphy in mice bearing 10 to 14 mm tumors was conducted at 5, 30, 60, 120, 240 min and 24 hrs postinjection of 111 In-DTPA-paclitaxel (3.7 MBq) or 111 In-DTPA as a control tracer. The tumor uptakes (% injection dose/pixel) were determined. The growth delay of OCA 1, MCA-4, FSA and SCC VII tumors was 13.6, 4.0, -0.02 and -0.28 days, respectively. In other words, OCA 1 and MCA-4 were paclitaxel-sensitive tumors, whereas FSA and SCC VII were paclitaxel-resistant tumors. The tumor uptakes at 24 hrs postinjection of In-111 DTPA paclitaxel of OCA 1, MCA-4, FSA and SCC VII were 1.0 x 10 -3 , 1.6 x 10 -3 , 2.2 x 10 -3 and 9.0 x 10 -3 % injection dose/pixel, respectively. There was no correlation between the response to chemotherapy with paclitaxel and the tumor uptakes of 111 In-DTPA-paclitaxel. Scintigraphy with 111 In-DTPA-paclitaxel could not predict the response to paclitaxel chemotherapy. Although there was significant accumulation of the paclitaxel in the tumor cells, additional mechanisms must be operative for the agent to be effective against the neoplasm. 111 In-DTPA-paclitaxel activity is apparently different from that of paclitaxel with Cremophor. (author)

  9. Randomized Study of Concurrent Carboplatin, Paclitaxel, and Radiotherapy with or Without Prior Induction Chemotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Gouda, Y.S.; Eldeeb, N.A.; Omar, A.M.; Kohail, H.M.; El-Geneidy, M.M.; Elkerm, Y.M.

    2006-01-01

    Background: Multiple concepts of combined modality therapy for locally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemo-radiotherapy, and radiation only. To date, combined modality therapy specially the use of concomitant chemo-radiotherapy has led to promising results and was shown to be superior to radiotherapy alone in phase II studies. However the optimum chemo-therapeutic regimen to be used as well as the benefit of induction chemotherapy before concomitant chemo-radiotherapy are yet to be determined. Based on these observations, we investigated the use of paclitaxel and carboplatin concomitantly with radiotherapy and the benefit of prior two cycles induction chemotherapy. Materials and Methods: In this trial 50 patients with locally advanced inoperable non small cell lung cancer, good performance status and minimal weight loss have been randomized into 3 groups each of 20 patients. Group A received induction 2 cycles paclitaxel (175 mg/m 2 ) and carboplatin (AUC 6) on day I and 28 th followed by concomitant paclitaxel (45 mg/m 2 ) and carboplatin (AUC 2) weekly with radiotherapy. Group B received concomitant carboplatin, paclitaxel (same doses as in group A) and radiotherapy with no prior induction chemotherapy. Group C received only radiotherapy to a total dose of 60 Gy in conventional fractionation. Results: A total of 60 patients were enrolled in this study between 1998 and 2000. Pretreatment characteristics, including age, gender, performance status, histological features and stage were comparable in each group. The incidence of oesophagi tis was significantly higher in group A and B than in group C (ρ=0.023). Hematological toxicities was also significantly higher in group A and B than in group C (ρ=0.003). The response rate was significantly higher in group A and B than in group C (75%,79%, and 40% respectively) (ρ =0.020). The time to in-field progresion was significantly

  10. Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

    Science.gov (United States)

    González-Martín, A J; Calvo, E; Bover, I; Rubio, M J; Arcusa, A; Casado, A; Ojeda, B; Balañá, C; Martínez, E; Herrero, A; Pardo, B; Adrover, E; Rifá, J; Godes, M J; Moyano, A; Cervantes, A

    2005-05-01

    The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

  11. Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma.

    Science.gov (United States)

    Huang, Yan; Liang, Wenhua; Yang, Yunpeng; Zhao, Liping; Zhao, Hongyun; Wu, Xuan; Zhao, Yuanyuan; Zhang, Yang; Zhang, Li

    2016-07-13

    This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab (®)-paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m(2) on day 1; 2) IV nab-paclitaxel 140 mg/m(2) on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m(2) on day 1. Treatment continued for 4-6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6-12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. ClinicalTrials.gov ID: NCT01735409 . The trial was registered on November 20th, 2012.

  12. Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Huang, Yan; Liang, Wenhua; Yang, Yunpeng; Zhao, Liping; Zhao, Hongyun; Wu, Xuan; Zhao, Yuanyuan; Zhang, Yang; Zhang, Li

    2016-01-01

    This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab ® -paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m 2 on day 1; 2) IV nab-paclitaxel 140 mg/m 2 on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m 2 on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m 2 on day 1. Treatment continued for 4–6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6–12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. ClinicalTrials.gov ID: NCT01735409. The trial was registered on November 20th, 2012. The online version of this article (doi:10.1186/s12885

  13. Bioadhesive drug delivery system using glyceryl monooleate for the intravesical administration of paclitaxel.

    Science.gov (United States)

    Lee, Seung-Ju; Kim, Sae Woong; Chung, Hesson; Park, Yeong Taek; Choi, Young Wook; Cho, Yong-Hyun; Yoon, Moon Soo

    2005-10-01

    Many reports have shown that the efficacy of intravesical therapy for bladder cancer is in part limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the absorption of intravesically administered paclitaxel in a rabbit model of bladder cancer. Urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120 min with paclitaxel (500 microg/20 ml) by intravesical instillation. Two formulations of GMO/paclitaxel were evaluated using different proportions of water, 15 and 30%, and Taxol was used as a control. Animals were observed for clinical signs of toxicity and necropsy was performed. 120 min after instillation, the bladder was emptied and excised. In the urine, paclitaxel concentration was decreased by 39.6 and 41.2% in the two experimental groups and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in both experimental groups, but 11% in the control group. The concentration then declined exponentially in the underlying capillary-perfused tissues, reaching equilibrium at a depth of 1,400-1,700 microm. The plasma concentrations were extremely low compared with concentrations in urine and bladder tissues and were not associated with clinical toxicity. We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy. Copyright 2005 S. Karger AG, Basel.

  14. Cost-Benefit Analysis of Nanoparticle Albumin-Bound Paclitaxel versus Solvent-Based Paclitaxel for the Treatment of Metastatic Breast Cancer in the United States

    Science.gov (United States)

    Vichansavakul, Kittaya

    had some limitations because they were conducted from a narrow perspective such as payer and provider point of views. The studies also considered only direct costs in their analysis. In fact, conducting economic evaluations from a narrow perspective and leaving out indirect costs might undermine the true benefit of the interventions for society. A cost-benefit analysis measures all costs and benefits in monetary units. It incorporates both health outcomes gained from individuals and the value gained to society in order to maximize the usage of resources effectively. This thesis conducted a cost-benefit analysis to compare nab-paclitaxel and generic paclitaxel in treating metastatic breast cancer from a societal perspective in the United States. The results showed that nab-paclitaxel is a cost-benefit strategy regardless of the different costs and benefits due to the extra 3 years of living it provides. In all models, when nab-paclitaxel was compared to generic paclitaxel, nab-paclitaxel showed cost-benefit to society. However, the results of generic paclitaxel were dependent on the total medical costs. Performing a cost-benefit analysis of nab-paclitaxel from a societal perspective is important to understand the true benefit of interventions. Furthermore, considering both direct and indirect costs, as well as benefits, of this drug is vital because the economic profile of nab-paclitaxel would be improved.

  15. 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...

  16. Potentiation of ovarian OCa-1 tumor radioresponse by poly (L-glutamic acid)-paclitaxel conjugate

    International Nuclear Information System (INIS)

    Li Chun; Ke Shi; Wu Qingping; Tansey, Wayne; Hunter, Nancy; Buchmiller, Lara M.; Milas, Luka; Charnsangavej, Chusilp; Wallace, Sidney

    2000-01-01

    Purpose: It has been shown that paclitaxel (TXL) can strongly enhance tumor cells' sensitivity to radiation. We examined whether the radiosensitizing effect of paclitaxel can be further enhanced when it is delivered systemically as a polymer-drug conjugate that provides enhanced tumor uptake and prolonged release of TXL in the tumor. Methods and Materials: C3Hf/Kam mice bearing 8-mm murine ovarian OCa-1 tumors were treated with i.v.-injected Poly(L-glutamic acid)-paclitaxel (PG-TXL) at an equivalent TXL dose of 80 mg/kg, followed 24 h later by single doses of local radiation ranging from 5 to 15 Gy. To determine how long the radiopotentiation persisted at extended times after PG-TXL administration, mice with OCa-1 tumors were given i.v. PG-TXL and 4, 24, 48, 72, 120, or 168 h later their tumors were irradiated at a dose of 10 Gy. Antitumor activity was determined by delay in tumor growth. Cell cycle distribution was assayed using flow cytometry. Tumor vascular volume was estimated using Tc-99 m-labeled red blood cells. Results: PG-TXL strongly potentiated the radioresponse of the OCa-1 tumor. The enhancement factors ranged from 2.79 to 4.28, depending on radiation dose, when PG-TXL preceded radiation by 24 h. The enhancement factor derived from radiation dose-response curves was as high as 5.13. The radiosensitizing effect of PG-TXL was also dependent on the interval between PG-TXL administration and radiation delivery, with greater enhancement been observed when the interval was decreased. The percentage of G2/M cells was significantly increased to 21.4% 48 h after PG-TXL but declined to a preinjection level of 14.8% 72 h after PG-TXL. PG-TXL only moderately increased the tumor vascular volume by 37% 24 h after PG-TXL administration. Conclusion: PG-TXL markedly potentiated response of OCa-1 tumor to radiation. When compared to literature data obtained from the same tumor model used here, PG-TXL exhibited stronger radiosensitization effect than TXL. Although its

  17. Nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreatic cancer: utility and experience from the clinic

    Directory of Open Access Journals (Sweden)

    Kundranda MN

    2016-01-01

    Full Text Available Madappa N Kundranda, Tomislav Dragovich Division of Hematology and Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA Abstract: Pancreatic ductal adenocarcinoma remains one of the deadliest epithelial cancers, primarily due to late diagnosis, early metastasis and the lack of effective treatments. With recent advances in systemic therapies, the median survival for metastatic disease has essentially doubled to approximately 1 year, and a significant number of patients are receiving multiple lines of therapy. One such first-line therapy is the combination of gemcitabine with nab-paclitaxel, which was approved by the US Food and Drug Administration in 2013. This standard option is now serving as a backbone to other novel combinations. In this review, we focus on the development of this combination, its clinical utility, and real-life experiences of managing patients with metastatic pancreatic ductal adenocarcinoma receiving gemcitabine and nab-paclitaxel. Keywords: pancreatic ductal adenocarcinoma, nab-paclitaxel, MPACT trial, PRODIGE 4/ACCORD 11 trial

  18. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

    Science.gov (United States)

    Hoskins, P; Vergote, I; Cervantes, A; Tu, D; Stuart, G; Zola, P; Poveda, A; Provencher, D; Katsaros, D; Ojeda, B; Ghatage, P; Grimshaw, R; Casado, A; Elit, L; Mendiola, C; Sugimoto, A; D'Hondt, V; Oza, A; Germa, J R; Roy, M; Brotto, L; Chen, D; Eisenhauer, E A

    2010-10-20

    Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and

  19. Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier.

    Science.gov (United States)

    Teow, Huey Minn; Zhou, Zhengyuan; Najlah, Mohammad; Yusof, Siti R; Abbott, N Joan; D'Emanuele, Antony

    2013-01-30

    The aim of this study was to investigate the ability of a third-generation (G3) polyamidoamine (PAMAM) dendrimer-based carrier to enhance the permeability of paclitaxel (pac) and to overcome cellular barriers. G3 dendrimers were surface modified with lauryl chains (L) and conjugated with paclitaxel (pac) via a glutaric anhydride (glu) linker, followed by labeling with FITC. Biological evaluation of the dendrimer and conjugates was conducted using the human colon adenocarcinoma cell line (Caco-2) and primary cultured porcine brain endothelial cells (PBECs). LDH assay was used to evaluate the cytotoxicity of the dendrimer and conjugates. Cytotoxicity studies showed that the conjugation of lauryl chains and paclitaxel on G3 dendrimer significantly (pdendrimer-drug conjugates demonstrated an increase in the apparent permeability coefficient (P(app)) in both apical to basolateral A→B and basolateral to apical B→A directions across both cell monolayers compared to unmodified G3 and free drug. The B→A P(app) of paclitaxel was significantly (ptransporter system in both cell models. L6-G3-glu-pac conjugate had approximately 12-fold greater permeability across both cell monolayers than that of paclitaxel alone. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Survival in women with ovarian cancer before and after the introduction of adjuvant paclitaxel; a 25-year, single institution review.

    LENUS (Irish Health Repository)

    Shireen, R

    2012-02-01

    Adjuvant chemotherapy regime for ovarian cancer patients remains to be a contentious issue. The aim of this study was to compare the overall and progression-free survival of women with ovarian cancer before and after introduction of paclitaxel in our unit in 1992. A sample of 112 women who received adjuvant therapy following surgery for ovarian cancer was collected, 68 (61%) received platinum+alkylating agent before 1992 and later 44 (39%) received platinum+paclitaxel. Five-year survival was same in both treatment groups when there was no macroscopic disease after surgery (78% versus 70%) and when residual disease was <2 cm (50% versus 40%). Survival was greater in women with residual disease >2 cm in the platinum+paclitaxel group (50% versus 24%), (p = 0.04). However, progression-free survival was similar in both groups irrespective of stage or residual volume of disease. Therefore consideration to selective use of paclitaxel could reduce patient morbidity and costs significantly.

  1. Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer.

    Science.gov (United States)

    Slingerland, Marije; Guchelaar, Henk-Jan; Rosing, Hilde; Scheulen, Max E; van Warmerdam, Laurence J C; Beijnen, Jos H; Gelderblom, Hans

    2013-12-01

    Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties. Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration. Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa. Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel Cmax values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia. At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil. © 2013 Elsevier HS Journals, Inc. All rights reserved.

  2. Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.

    Science.gov (United States)

    Forrest, John K; Lansky, Alexandra J; Meller, Stephanie M; Hou, Liming; Sood, Poornima; Applegate, Robert J; Wang, John C; Skelding, Kimberly A; Shah, Aakar; Kereiakes, Dean J; Sudhir, Krishnankutty; Cristea, Ecaterina; Yaqub, Manejeh; Stone, Gregg W

    2013-06-01

    The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial. Copyright © 2013 Elsevier Inc. All

  3. Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel

    Directory of Open Access Journals (Sweden)

    Muh. Akbar Bahar

    2013-01-01

    Full Text Available Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of commonly used chemotherapeutic agents. However, there are no effective strategies to treat the neuropathy. We examined whether Goshajinkigan, a herbal medicine, would prevent paclitaxel-induced allodynia without affecting the anticancer action in mice. Murine breast cancer 4T1 cells were inoculated into the mammary fat pad. Paclitaxel (10 and 20 mg/kg, intraperitoneal, alternate day from day 7 postinoculation inhibited the tumor growth, and Goshajinkigan (1 g/kg, oral, daily from day 2 postinoculation did not affect the antitumor action of paclitaxel. Mechanical allodynia developed in the inoculated region due to tumor growth and in the hind paw due to paclitaxel-induced neuropathy. Paclitaxel-induced allodynia was markedly prevented by Goshajinkigan, although tumor-associated allodynia was not inhibited by Goshajinkigan. These results suggest that Goshajinkigan prevents paclitaxel-induced peripheral neuropathy without interfering with the anti-cancer action of paclitaxel.

  4. Paclitaxel and concurrent radiation for gastric cancer

    International Nuclear Information System (INIS)

    Safran, Howard; Wanebo, Harry J.; Hesketh, Paul J.; Akerman, Paul; Ianitti, David; Cioffi, William; Di Petrillo, Thomas; Wolf, Brian; Koness, James; McAnaw, Robert; Moore, Todd; Chen, M.-H.; Radie-Keane, Kathy

    2000-01-01

    Purpose: To determine the activity and toxicity of paclitaxel and concurrent radiation for gastric cancer. Methods and Materials: Twenty-seven patients were studied. Twenty-five had proximal gastric cancers, two had distal cancers. Eight had esophageal extension, 6 had celiac adenopathy, and 7 had retroperitoneal adenopathy. Patients received paclitaxel, 50 mg/m 2 by 3-hour intravenous (IV) infusion, weekly, on days 1, 8, 15, 22, and 29. Radiation was administered concurrently to a total dose of 45.0 Gy, in 1.80 Gy fractions, for 25 treatments. Patients who were medically or surgically inoperable received a sixth week of paclitaxel with a radiation boost to 50.4 Gy. Results: Esophagitis and gastritis were the most important toxicities, Grade 3 in four patients (15%), and Grade 4 in three patients (11%). Five patients (19%) had Grade 3 nausea. The overall response rate was 56%, including three patients (11%) with a complete response. The 2-year progression-free and overall survival rates were 29% and 31%, respectively. Conclusion: Concurrent paclitaxel and radiation demonstrates substantial local-regional activity in gastric cancer. Future investigations combining paclitaxel and radiation with other local-regional and systemic treatments are warranted

  5. Comparing abrupt and gradual smoking cessation: a randomized trial.

    Science.gov (United States)

    Etter, Jean-François

    2011-11-01

    To compare abrupt and gradual smoking cessation. Randomized trial and observational study, Internet, 2007-2010. Smokers with no strong preference for abrupt or gradual quitting were randomly assigned to quitting immediately (n=472), or to gradually reducing their cigarette consumption over 2 weeks and then quit (n=502). Smokers who strongly preferred to quit abruptly were instructed to do so immediately (n=2456), those who strongly preferred gradual were instructed to reduce their cigarette consumption over 2 weeks, then quit (n=1801). Follow-up was conducted 4 weeks after target quit dates. Those who preferred abrupt quitting were the most motivated to quit and the most confident in their ability to quit. At follow-up, quit rates were 16% in those who preferred abrupt cessation, 7% in those who preferred gradual cessation and 9% in those who had no preference (pmotivation to quit and confidence in ability to quit: those who had low levels of motivation or low levels of confidence were more likely to quit at follow-up if they preferred and used abrupt rather than gradual. In those who had no strong preference for either method, abrupt and gradual produced similar results. Those who preferred and used the abrupt method were more likely to quit than those who preferred and used the gradual method, in particular when they had low motivation and confidence. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Clinical trial of osteoarthritis jamu formula compare to piroxicam

    Directory of Open Access Journals (Sweden)

    Danang Ardiyanto

    2016-12-01

    is a lack of evidence of its efficacy and safety. The objectives of study were to investigate the efficacy and safety of  a traditional formula for OA. Methods: Design of the study was a randomized clinical trial (RCT involved 123 patients (subjects for 28 days intervention. This study was conducted between March - December 2014 with 30 physicians were participated at 20 regencies in Indonesia. The variables measured were VAS score, PGAP functional status assessment (FSA, and Short Form (SF-36 to assess jamu efficacy in comparison to piroxicam. To evaluate the safety of jamu formula using values of SGOT, SGPT, BUN, and creatinine. Result: The jamu formula administration effects can reduce VAS significantly  (p<0.05  if it was compared to baseline. FSA score of jamu formula group was decreased significantly (p=0.000 when compared to the start of intervention. Short Form (SF-36 of jamu formula group were significantly improved when compared with baseline value. The result of the three parameters between jamu group and piroxicam group should not significantly different. There was no difference in those parameters between both groups (p>0.05. In biological parameters, SGPT, SGOT, BUN, and creatinine level, showed normal range in both groups. Conclusion: This study showed that the efficacy and safety of jamu formula was clinically comparable to piroxicam after 28 days of treatment. Keywords: efficacy, safety, RCT, jamu formula  

  7. Minoxidil is a potential neuroprotective drug for paclitaxel-induced peripheral neuropathy

    Science.gov (United States)

    Chen, Yi-Fan; Chen, Li-Hsien; Yeh, Yu-Min; Wu, Pei-Ying; Chen, Yih-Fung; Chang, Lian-Yun; Chang, Jang-Yang; Shen, Meng-Ru

    2017-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. No medication has been shown to be effective in the treatment of CIPN. This study aims to integrate the image-based high-content screening, mouse behavior models and mechanistic cell-based assays to discover potential neuroprotective drugs. Among screened compounds, minoxidil showed the most potent neuroprotective effect against paclitaxel, with regard to neurite outgrowth of dorsal root ganglia (DRG). Minoxidil protected mice from thermal insensitivity and alleviated mechanical allodynia in paclitaxel-treated mice. The ultrastructure and quantified G-ratio of myelin integrity of sciatic nerve tissues supported the observations in mouse behavioral tests. The mechanistic study on DRG neurons suggested that minoxidil suppressed neuroinflammation and remodeled the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, minoxidil showed a synergistic anti-tumor effect with paclitaxel both in tumor xenograft models of cervical and breast cancer. Interestingly, the quantitative assays on hair length and hair growth both exhibited that minoxidil significantly improved the hair quality after chemotherapy. Since minoxidil is a drug approved by the Food and Drug Administration (FDA), the safety and biocompatibility are well documented. The immediate next step is to launch an early-stage clinical trial intending to prevent CIPN by minoxidil. PMID:28349969

  8. Pharmaceutical development of an oral tablet formulation containing a spray dried amorphous solid dispersion of docetaxel or paclitaxel

    NARCIS (Netherlands)

    Sawicki, Emilia; Beijnen, Jos H|info:eu-repo/dai/nl/071919570; Schellens, Jan H M|info:eu-repo/dai/nl/073926272; Nuijen, Bastiaan

    2016-01-01

    Previously, it was shown in Phase I clinical trials that solubility-limited oral absorption of docetaxel and paclitaxel can be drastically improved with a freeze dried solid dispersion (fdSD). These formulations, however, are unfavorable for further clinical research because of limitations in

  9. Microwave-assisted efficient conjugation of nanodiamond and paclitaxel.

    Science.gov (United States)

    Hsieh, Yi-Han; Liu, Kuang-Kai; Sulake, Rohidas S; Chao, Jui-I; Chen, Chinpiao

    2015-01-01

    Nanodiamond has recently received considerable attention due to the various possible applications in medical field such as drug delivery and bio-labeling. For this purpose suitable and effective surface functionalization of the diamond material are required. A versatile and reproducible surface modification method of nanoscale diamond is essential for functionalization. We introduce the input of microwave energy to assist the functionalization of nanodiamond surface. The feasibility of such a process is illustrated by comparing the biological assay of ND-paclitaxel synthesized by conventional and microwave irradiating. Using a microwave we manage to have approximately doubled grafted molecules per nanoparticle of nanodiamond. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Paclitaxel and doxorubicin in metastatic breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T

    1996-01-01

    For the past decades the anthracyclines have been regarded as among the most active drugs for the treatment of metastatic breast cancer. However, the 5-year survival rate in patients with stage IV breast cancer continues to be below 20%, and new active drugs and drug combinations clearly must...... be explored. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be highly effective in treating patients with advanced breast cancer, including those with anthracycline-resistant breast cancer, a fact that has led to efforts to combine paclitaxel and anthracyclines...

  11. Randomized comparison between intracoronary β-radiation brachytherapy and implantation of paclitaxel-eluting stents for the treatment of diffuse in-stent restenosis

    International Nuclear Information System (INIS)

    Schukro, Christoph; Syeda, Bonni; Kirisits, Christian; Schmid, Rainer; Pichler, Philipp; Pokrajac, Boris; Lang, Irene; Poetter, Richard; Glogar, Dietmar

    2007-01-01

    Background and purpose: Intracoronary brachytherapy was the primary therapeutic option for the treatment of in-stent restenosis (ISR) during the last years. Especially for the treatment of diffuse ISR (lesions >10 mm), β-source brachytherapy was significantly superior to singular balloon angioplasty. Despite lacking clinical database, the implantation of drug eluting stents recently became a common procedure for the treatment of ISR. This randomized trial aimed to compare the efficacy of β-brachytherapy with β-radioisotopes 90 Sr/ 90 Y and paclitaxel-eluting stent implantation for the treatment of diffuse ISR. Material and methods: Thirty-seven patients with diffuse ISR were randomly assigned to β-brachytherapy after balloon angioplasty (Beta-Cath TM in 17 patients) or paclitaxel-eluting stent implantation (Taxus-Express2 TM in 20 patients). Six-month clinical follow-up was obtained for all patients, while angiographic follow-up was available for 30 patients. Results: Binary ISR (restenosis >50%) within target segment was observed in three patients treated with Beta-Cath TM , of which one needed target segment revascularisation for recurrent ISR, whereas no significant restenosis occurred in the patients treated with Taxus-Express2 TM (P = 0.037). No further major adverse cardiac (target segment revascularisation, myocardial infarction, death) was found in either group (P = NS). Stent implantation was the more time-saving (31 ± 11 min versus 60 ± 23 min, P TM arm, we found no difference in clinical outcome after implantation of paclitaxel-eluting stents for the treatment of diffuse ISR when compared to β-brachytherapy

  12. Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel

    OpenAIRE

    Bahar, Muh. Akbar; Andoh, Tsugunobu; Ogura, Keisuke; Hayakawa, Yoshihiro; Saiki, Ikuo; Kuraishi, Yasushi

    2013-01-01

    Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of commonly used chemotherapeutic agents. However, there are no effective strategies to treat the neuropathy. We examined whether Goshajinkigan, a herbal medicine, would prevent paclitaxel-induced allodynia without affecting the anticancer action in mice. Murine breast cancer 4T1 cells were inoculated into the mammary fat pad. Paclitaxel (10 and 20 mg/kg, intraperitoneal, alternate day from day 7 postinoculation) ...

  13. Investigation of 3′-debenzoyl-3′-(3-([124I]-iodobenzoyl))paclitaxel analog as a radio-tracer to study multidrug resistance in vivo

    International Nuclear Information System (INIS)

    Sajjad, M.; Riaz, U.; Yao, R.; Bernacki, R.J.; Abouzied, M.; Erb, D.A.; Chaudhary, N.D.; Veith, J.M.; Georg, G.I.; Nabi, H.A.

    2012-01-01

    A study was carried out to identify a suitable radioactive paclitaxel analog and to use it to investigate tumor multidrug resistance in vivo. 3′-Debenzoyl-3′-(3-([ 124 I]-iodobenzoyl))paclitaxel was prepared by aromatic iodination of 3′-debenzoyl-3′-(3-trimethylstannylbenzoyl)paclitaxel. Uptake of the labeled paclitaxel analog in nude mice bearing tumor with the paclitaxel sensitive cancer cell lines MCF7 and MDA-435/LCC6(WT), and multidrug resistant cell lines NCI/ADR-RES and MDA-435/LCC6(MDR), was studied. There was no difference in drug level between the sensitive and resistant MDA-435/LCC6 tumors at 6 h post-injection. However, at 6 h, there was a significant increase in drug level for the MCF7 tumor as compared with the NCI/ADR-RES tumor, presumably due to increased drug retention. At 24 h, drug uptake/retention was significantly higher in both sensitive tumor cell lines as compared to their drug resistant counterparts. Pretreatment of mice with MDR transport modulators, Cyclosporine or tRA 96029, did not increase the level of labeled paclitaxel analog in the drug resistant MDA-435/LCC6(MDR) tumor. On the other hand, at 24 h Cyclosporine apparently increased analog level in the drug sensitive MDA-435/LCC6(WT) tumor, aiding drug imaging studies. - Highlights: ► 3′-Debenzoyl-3′-(3-iodobenzoyl)paclitaxel cytotoxicity was comparable to paclitaxel. ► 3′-Debenzoyl-3′-(3-([ 124 I]-iodobenzoyl)paclitaxel was synthesized. ► Uptake of the drug was higher in sensitive tumor compared to the resistant tumor. ► The Pgp-modulators had a positive effect on drug-sensitive tumor. ► The sensitive tumor was visible in images obtained using micoPET.

  14. Acute migraine therapy: recent evidence from randomized comparative trials

    DEFF Research Database (Denmark)

    Mett, A.; Tfelt-Hansen, P.

    2008-01-01

    (1) A wide array of data regarding acute migraine treatment are available, but few trials strictly adhere to International Headache Society guidelines for patient inclusion criteria. (2) Triptans appear to have similar efficacy profiles, but among newer triptans, almotriptan offers improved...

  15. The battle of “nano” paclitaxel

    NARCIS (Netherlands)

    Sofias, Alexandros Marios; Dunne, Michael; Storm, Gert; Allen, Christine

    2017-01-01

    Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best-selling cancer drug of all time with annual

  16. 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.

  17. Ototoxicity of paclitaxel in rat cochlear organotypic cultures

    International Nuclear Information System (INIS)

    Dong, Yang; Ding, Dalian; Jiang, Haiyan; Shi, Jian-rong; Salvi, Richard; Roth, Jerome A.

    2014-01-01

    Paclitaxel (taxol) is a widely used antineoplastic drug employed alone or in combination to treat many forms of cancer. Paclitaxel blocks microtubule depolymerization thereby stabilizing microtubules and suppressing cell proliferation and other cellular processes. Previous reports indicate that paclitaxel can cause mild to moderate sensorineural hearing loss and some histopathologic changes in the mouse cochlea; however, damage to the neurons and the underlying cell death mechanisms are poorly understood. To evaluate the ototoxicity of paclitaxel in more detail, cochlear organotypic cultures from postnatal day 3 rats were treated with paclitaxel for 24 or 48 h with doses ranging from 1 to 30 μM. No obvious histopathologies were observed after 24 h treatment with any of the paclitaxel doses employed, but with 48 h treatment, paclitaxel damaged cochlear hair cells in a dose-dependent manner and also damaged auditory nerve fibers and spiral ganglion neurons (SGN) near the base of the cochlea. TUNEL labeling was negative in the organ of Corti, but positive in SGN with karyorrhexis 48 h after 30 μM paclitaxel treatment. In addition, caspase-6, caspase-8 and caspase-9 labeling was present in SGN treated with 30 μM paclitaxel for 48 h. These results suggest that caspase-dependent apoptotic pathways are involved in paclitaxel-induced damage of SGN, but not hair cells in cochlea. - Highlights: • Paclitaxel was toxic to cochlear hair cells and spiral ganglion neurons. • Paclitaxel-induced spiral ganglion degeneration was apoptotic. • Paclitaxel activated caspase-6, -8 and -8 in spiral ganglion neurons

  18. Ototoxicity of paclitaxel in rat cochlear organotypic cultures

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yang [Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Center for Hearing and Deafness, University at Buffalo, NY 14214 (United States); Ding, Dalian; Jiang, Haiyan [Center for Hearing and Deafness, University at Buffalo, NY 14214 (United States); Shi, Jian-rong [Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Salvi, Richard [Center for Hearing and Deafness, University at Buffalo, NY 14214 (United States); Roth, Jerome A., E-mail: jaroth@buffalo.edu [Department of Pharmacology and Toxicology, University at Buffalo, NY 14214 (United States)

    2014-11-01

    Paclitaxel (taxol) is a widely used antineoplastic drug employed alone or in combination to treat many forms of cancer. Paclitaxel blocks microtubule depolymerization thereby stabilizing microtubules and suppressing cell proliferation and other cellular processes. Previous reports indicate that paclitaxel can cause mild to moderate sensorineural hearing loss and some histopathologic changes in the mouse cochlea; however, damage to the neurons and the underlying cell death mechanisms are poorly understood. To evaluate the ototoxicity of paclitaxel in more detail, cochlear organotypic cultures from postnatal day 3 rats were treated with paclitaxel for 24 or 48 h with doses ranging from 1 to 30 μM. No obvious histopathologies were observed after 24 h treatment with any of the paclitaxel doses employed, but with 48 h treatment, paclitaxel damaged cochlear hair cells in a dose-dependent manner and also damaged auditory nerve fibers and spiral ganglion neurons (SGN) near the base of the cochlea. TUNEL labeling was negative in the organ of Corti, but positive in SGN with karyorrhexis 48 h after 30 μM paclitaxel treatment. In addition, caspase-6, caspase-8 and caspase-9 labeling was present in SGN treated with 30 μM paclitaxel for 48 h. These results suggest that caspase-dependent apoptotic pathways are involved in paclitaxel-induced damage of SGN, but not hair cells in cochlea. - Highlights: • Paclitaxel was toxic to cochlear hair cells and spiral ganglion neurons. • Paclitaxel-induced spiral ganglion degeneration was apoptotic. • Paclitaxel activated caspase-6, -8 and -8 in spiral ganglion neurons.

  19. Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma.

    Directory of Open Access Journals (Sweden)

    Annette Pflugfelder

    Full Text Available BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c received CP as first-line treatment, 41 patients (90.2% M1c had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD (49 weeks compared to patients with progressive disease (18 weeks. CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.

  20. Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel or eribulin followed by doxorubicin and cyclophosphamide in women with locally advanced HER2-negative breast cancer: NSABP Foundation Study FB-9.

    Science.gov (United States)

    Abraham, Jame; Robidoux, André; Tan, Antoinette R; Limentani, Steven; Sturtz, Keren; Shalaby, Ibrahim; Alcorn, Hope; Buyse, Marc E; Wolmark, Norman; Jacobs, Samuel A

    2015-07-01

    Locally advanced breast cancer (LABC) is a good setting in which to monitor response to neoadjuvant chemotherapy, to downsize the tumor (which facilitates breast-conserving surgery), and to test newer agents in untreated patients. Eribulin (E) has shown activity in patients who have undergone previous taxane, anthracycline, and capecitabine treatment. We aimed to evaluate the neoadjuvant use of E followed by doxorubicin and cyclophosphamide (AC) in patients with HER2-negative LABC, using as a control a randomized group of women who received weekly paclitaxel (WP). Fifty women with LABC were accrued January-August 2013. Patients were randomized (1:2) to receive either WP (N = 19) for 12 treatments or E (N = 31) every 3 weeks for 4 cycles followed by AC every 3 weeks for 4 cycles before surgery. 17/19 patients who took WP and 25/30 who took E completed all cycles. Patients were evaluated by clinical examination and breast MRI at baseline and after completion of E or WP. Surgical pCR in breast and lymph nodes was determined by a local pathologist following chemotherapy. Forty-nine patients received ≥1 dose of neoadjuvant chemotherapy and are included in this analysis. Forty-eight underwent surgery; one had disease that was inoperable (on E) and is included as no-pCR patient. 17/19 of these patients who took WP completed 12 doses; 28/30 on E completed 4 cycles. Six discontinued treatment on WP, E, or AC. Both treatments were well tolerated. pCR on WP = 5/19(26 %) and on E = 5/30(17 %). Both regimens were equally well tolerated with no unexpected toxicities. pCR did not suggest higher activity with E than with other standard regimens in these LABC patients.

  1. Paclitaxel Causes Electrophysiological Changes in the Anterior Cingulate Cortex via Modulation of the γ-Aminobutyric Acid-ergic System.

    Science.gov (United States)

    Nashawi, Houda; Masocha, Willias; Edafiogho, Ivan O; Kombian, Samuel B

    The aim of this study was to elucidate any electrophysiological changes that may contribute to the development of neuropathic pain during treatment with the anticancer drug paclitaxel, particularly in the γ-aminobutyric acid (GABA) system. One hundred and eight Sprague-Dawley rats were used (untreated control: 43; vehicle-treated: 21, and paclitaxel-treated: 44). Paclitaxel (8 mg/kg) was administered intraperitoneally on 2 alternate days to induce mechanical allodynia. The rats were sacrificed 7 days after treatment to obtain slices of the anterior cingulate cortex (ACC), a brain region involved in the central processing of pain. Field excitatory postsynaptic potentials (fEPSPs) were recorded in layer II/III of ACC slices, and stimulus-response curves were constructed. The observed effects were pharmacologically characterized by bath application of GABA and appropriate drugs to the slices. The paclitaxel-treated rats developed mechanical allodynia (i.e. reduced withdrawal threshold to mechanical stimuli). Slices from paclitaxel-treated rats produced a significantly higher maximal response (Emax) than those from untreated rats (p GABA (0.4 µM) reversed this effect and returned the excitability to a level similar to control. Pretreatment of the slices with the GABAB receptor blocker CGP 55845 (50 µM) increased Emax in slices from untreated rats (p GABA deficit in paclitaxel-treated rats compared to untreated ones. Such a deficit could contribute to the pathophysiology of paclitaxel-induced neuropathic pain (PINP). Thus, the GABAergic system might be a potential therapeutic target for managing PINP. © 2016 S. Karger AG, Basel.

  2. The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole.

    Science.gov (United States)

    Prajna, N Venkatesh; Krishnan, Tiruvengada; Mascarenhas, Jeena; Rajaraman, Revathi; Prajna, Lalitha; Srinivasan, Muthiah; Raghavan, Anita; Oldenburg, Catherine E; Ray, Kathryn J; Zegans, Michael E; McLeod, Stephen D; Porco, Travis C; Acharya, Nisha R; Lietman, Thomas M

    2013-04-01

    To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis. This phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400. The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty. A total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycintreated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=0.18 logMAR; 95% CI, 0.30 to 0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=0.41 logMAR; 95% CI,0.61 to 0.20; P<.001; odds ratio for perforation=0.06; 95% CI, 0.01 to 0.28; P<.001), while non-Fusarium cases fared similarly (regression coefficient=0.02 logMAR; 95% CI, 0.17 to 0.13; P=.81; odds ratio for perforation=1.08; 95% CI, 0.48 to 2.43; P=.86). Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases. Voriconazole should not be used as monotherapy in filamentous keratitis. clinicaltrials.gov Identifier: NCT00996736

  3. A Randomized Trial Comparing Skin Antiseptic Agents at Cesarean Delivery.

    Science.gov (United States)

    Tuuli, Methodius G; Liu, Jingxia; Stout, Molly J; Martin, Shannon; Cahill, Alison G; Odibo, Anthony O; Colditz, Graham A; Macones, George A

    2016-02-18

    Preoperative skin antisepsis has the potential to decrease the risk of surgical-site infection. However, evidence is limited to guide the choice of antiseptic agent at cesarean delivery, which is the most common major surgical procedure among women in the United States. In this single-center, randomized, controlled trial, we evaluated whether the use of chlorhexidine-alcohol for preoperative skin antisepsis was superior to the use of iodine-alcohol for the prevention of surgical-site infection after cesarean delivery. We randomly assigned patients undergoing cesarean delivery to skin preparation with either chlorhexidine-alcohol or iodine-alcohol. The primary outcome was superficial or deep surgical-site infection within 30 days after cesarean delivery, on the basis of definitions from the Centers for Disease Control and Prevention. From September 2011 through June 2015, a total of 1147 patients were enrolled; 572 patients were assigned to chlorhexidine-alcohol and 575 to iodine-alcohol. In an intention-to-treat analysis, surgical-site infection was diagnosed in 23 patients (4.0%) in the chlorhexidine-alcohol group and in 42 (7.3%) in the iodine-alcohol group (relative risk, 0.55; 95% confidence interval, 0.34 to 0.90; P=0.02). The rate of superficial surgical-site infection was 3.0% in the chlorhexidine-alcohol group and 4.9% in the iodine-alcohol group (P=0.10); the rate of deep infection was 1.0% and 2.4%, respectively (P=0.07). The frequency of adverse skin reactions was similar in the two groups. The use of chlorhexidine-alcohol for preoperative skin antisepsis resulted in a significantly lower risk of surgical-site infection after cesarean delivery than did the use of iodine-alcohol. (Funded by the National Institutes of Health and Washington University School of Medicine in St. Louis; ClinicalTrials.gov number, NCT01472549.).

  4. Effect of kamikihito (TJ-137) on paclitaxel-induced olfactory neuropathy in vivo

    International Nuclear Information System (INIS)

    Yamamoto, Junpei

    2012-01-01

    A Kampo product, kamikihito (product name code: TJ-137), has ingredients that promote nerve growth. Paclitaxel, a cancer chemotherapeutic agent, is toxic to olfactory nerve cells in vivo. We found that TJ-137 is effective in reducing paclitaxel induced olfactory neuropathy in vivo. Female 7-week-old Bulb/c mice were fed food containing TJ-137, or control food, for 14 days before and after intravenous paclitaxel administration. 201 Tl uptake in nasal turbinates of TJ-137 treated mice (n=8) and control mice (n=9) was assessed by gamma spectrometry 6 hrs after nasal administration of 201 Tl. The epithelial changes in the nasal turbinates of mice were assessed by H and E and immunohistochemical staining for the olfactory marker protein (OMP). The accumulation of the neuronal tracer (Dextran tetramethylrhodamine) in the olfactory bulb was assessed in frozen sections of mice 48 hrs after nasal administration of the tracer. The epithelium of nasal turbinates of TJ-137 treated mice was less injured than that of the control mice after paclitaxel administration. The nasal epithelium was significantly thicker in TJ-137 treated mice compared to control mice (P=0.019). The accumulation of the neuronal tracer in the olfactory bulb was higher in the TJ-137 treated mice compared to controls. 201 Tl uptake per weight in nasal turbinate of TJ-137 treated mice was significantly higher than that of control mice (P=0.008). Pre-medication with TJ-137 (kamikihito) was effective in increasing olfactory nerve viability after paclitaxel administration in vivo. (author)

  5. STX140, but Not Paclitaxel, Inhibits Mammary Tumour Initiation and Progression in C3(1)/SV40 T/t-Antigen Transgenic Mice

    OpenAIRE

    Meyer-Losic, Florence; Newman, Simon P.; Day, Joanna M.; Reed, Michael J.; Kasprzyk, Philip G.; Purohit, Atul; Foster, Paul A.

    2013-01-01

    Despite paclitxael's clinical success, treating hormone-refractory breast cancer remains challenging. Paclitaxel has a poor pharmacological profile, characterized by a low therapeutic index (TIX) caused by severe dose limiting toxicities, such as neutropenia and peripheral neuropathy. Consequently, new drugs are urgently required. STX140, a compound previously shown to have excellent efficacy against many tumors, is here compared to paclitaxel in three translational in vivo breast cancer mode...

  6. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  7. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    Yang, Danbo; Yu, Lei; Van, Sang

    2010-01-01

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  8. Management of paclitaxel-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Manisha Bhutani

    2011-12-01

    Full Text Available Paclitaxel exerts its antitumor activity by promoting microtubule assembly and stabilizing microtubules. Microtubules are important for the development and maintenance of neurons. As a consequence, neurotoxicity is one of the drug’s major side effects. The risk of neurotoxicity depends on dose, duration and schedule of paclitaxel. Risk increases for patients with pre-existing conditions that may cause neuropathy (such as alcohol consumption, diabetes, or renal disease or with simultaneous or prior exposure to other neurotoxic chemotherapy such as platinum-based drugs, vinca alkaloids, immunomodulators, proteasome inhibitors, and epothilones. Patients with paclitaxel-induced neurotoxicity (PINT experience a constellation of symptoms over the course of treatment and beyond, ranging from mild to severe. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. Proprioceptive and motor effects become apparent as neuropathy becomes more advanced. These symptoms may be prolonged, severe, disabling, relatively resistant to intervention and adversely affect activities of daily living and thereby quality of life. Management is mainly symptomatic and supportive. Despite attempts to minimize PINT with changes in dose, vehicle, delivery systems, infusion schedule and premedication or co-treatment with neuroprotective agents, PINT remains dose-limiting in many instances and is a barrier to achieving the desired clinical response.

  9. Paclitaxel: new uses for an old drug

    Directory of Open Access Journals (Sweden)

    Zhang D

    2014-02-01

    Full Text Available Dongshan Zhang,1,2 Ruhao Yang,1 Shixuan Wang,2 Zheng Dong1,2 1Departments of Emergency Medicine and Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, GA, USA Abstract: Paclitaxel (Taxol, one of the most important anticancer drugs, has been used for therapy of different types of cancers. Mechanistically, paclitaxel arrests cell cycle and induces cell death by stabilizing microtubules and interfering with microtubule disassembly in cell division. Recently, it has been found that low-dose paclitaxel seems promising in treating non-cancer diseases, such as skin disorders, renal and hepatic fibrosis, inflammation, axon regeneration, limb salvage, and coronary artery restenosis. Future studies need to understand the mechanisms underlying these effects in order to design therapies with specificity. Keywords: taxol inflammation, fibrosis, coronary artery restenosis, limb salvage, kidney

  10. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  11. Toxic vessel reaction to an absorbable polymer-based paclitaxel-eluting stent in pig coronary arteries.

    Science.gov (United States)

    Jabara, Refat; Chronos, Nicolas; Tondato, Fernando; Conway, Damian; Molema, Warner; Park, Kenneth; Mabin, Tom; King, Spencer; Robinson, Keith

    2006-08-01

    The goal of this study was to evaluate a new drug-eluting stent (DES) comprising a bioabsorbable polymer eluting a moderate dose of paclitaxel in a clinically relevant animal model. Although DES limit restenosis, adverse vascular pathologies and toxicities continue to be of major concern. Optimization of DES components, especially completely absorbable polymers, may reduce these toxicities. Bare-metal (BM), absorbable polymer coating only (POLY), and polymer-based paclitaxel-eluting (PACL) stents were implanted in porcine coronary arteries using intravascular ultrasound (IVUS) to optimize stent apposition. The dose density of paclitaxel was 0.30-0.35 mcg/mm2, with in vitro elution studies demonstrating a gradual elution over 6-8 weeks. The animals were terminated at 1 week, 1 month and 3 months. Histopathologic and histomorphometric analyses were perform. The arteries with PACL showed extensive smooth muscle cell necrosis at 1 week and poor apposition of stent struts at 1 month (malapposition measured as gap width between strut and internal elastic lamina), with greater gap width compared to the BM and POLY groups (0.22 mm +/- 0.02 vs. 0.03 mm +/- 0.02 and 0.02 mm +/- 0.01, respectively; p stent malapposition and late neointimal thickening. Since the therapeutic window for paclitaxel may be narrower than currently inferred, thorough preclinical testing coupled with the polymer development process for stents eluting paclitaxel is needed.

  12. Clinical trial to compare tinnitus masking and tinnitus retraining therapy.

    Science.gov (United States)

    Henry, J A; Schechter, M A; Zaugg, T L; Griest, S; Jastreboff, P J; Vernon, J A; Kaelin, C; Meikle, M B; Lyons, K S; Stewart, B J

    2006-12-01

    Both tinnitus masking (TM) and tinnitus retraining therapy (TRT) can be effective therapies for amelioration of tinnitus. TM may be more effective for patients in the short term, but with continued treatment TRT may produce the greatest effects. Although TM and TRT have been used for many years, research has not documented definitively the efficacy of these methods. The present study was a controlled clinical trial to prospectively evaluate the clinical efficacy of these two methods for US military veterans with severe tinnitus. Over 800 veterans were screened to ensure that enrolled patients had tinnitus of sufficient severity to justify 18 months of individualized treatment. Qualifying patients (n=123) were placed quasi-randomly (alternating placement) into treatment with either TM or TRT. Treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated primarily using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index). Findings are presented from the three written questionnaires with respect to three categories of patients: describing tinnitus as a 'moderate,' 'big,' and 'very big' problem at baseline. Based on effect sizes, both groups showed considerable improvement overall. In general, TM effects remained fairly constant over time while TRT effects improved incrementally. For the patients with a 'moderate' and 'big' problem, TM provided the greatest benefit at 3 and 6 months; benefit to these TRT patients was slightly greater at 12 months, and much greater at 18 months. For patients with a 'very big' problem, TM provided the greatest benefit at 3 months. For these latter patients, results were about the same between groups at 6 months, and improvement for TRT was much greater at 12 months, with further gains at 18 months.

  13. Therapeutic effect of intravesical administration of paclitaxel solubilized with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) in an orthotopic bladder cancer model

    International Nuclear Information System (INIS)

    Tamura, Koetsu; Kikuchi, Eiji; Konno, Tomohiro; Ishihara, Kazuhiko; Matsumoto, Kazuhiro; Miyajima, Akira; Oya, Mototsugu

    2015-01-01

    To evaluate the effects of intravesical administration of paclitaxel (PTX-30W), which was prepared by solubilization with a water-soluble amphiphilic polymer composed of PMB30W, a copolymer of 2-methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate, in an orthotopic bladder cancer model. The cytotoxicities of PMB30W were examined in MBT-2 cell cultures and the results were compared with those of the conventional paclitaxel solubilizer Cremophor. In an orthotopic MBT-2 bladder cancer model, the effect of intravesical administration of PTX-30W was compared with that of paclitaxel solubilized with Cremophor (PTX-CrEL). The paclitaxel concentration in bladder tumors after the intravesical treatment was also evaluated using liquid chromatography tandem mass spectrometry (LC-MS/MS) system. In vitro, Cremophor exhibited dose-dependent cytotoxicity towards MBT-2 cells, whereas no cytotoxicity was observed with PMB30W. In the orthotopic bladder cancer model, intravesical administration of PTX-30W resulted in a significant reduction of bladder wet weight compared with that of PTX-CrEL. The paclitaxel concentration in bladder tumors after the intravesical treatment was significantly higher in PTX-30W treated mice than in PTX-CrEL treated mice. Intravesically administered PTX-30W can elicit stronger antitumor effects on bladder tumors than conventional paclitaxel formulated in Cremophor, presumably because of its better penetration into tumor cells. PTX-30W might be a promising antitumor agent for intravesical treatment of non-muscle invasive bladder cancer

  14. Cytotoxicity of Paclitaxel in biodegradable self-assembled core-shell poly(lactide-co-glycolide ethylene oxide fumarate) nanoparticles.

    Science.gov (United States)

    He, Xuezhong; Ma, Junyu; Mercado, Angel E; Xu, Weijie; Jabbari, Esmaiel

    2008-07-01

    Biodegradable core-shell polymeric nanoparticles (NPs), with a hydrophobic core and hydrophilic shell, are developed for surfactant-free encapsulation and delivery of Paclitaxel to tumor cells. Poly (lactide-co-glycolide fumarate) (PLGF) and Poly (lactide-fumarate) (PLAF) were synthesized by condensation polymerization of ultra-low molecular weight poly(L: -lactide-co-glycolide) (ULMW PLGA) with fumaryl chloride (FuCl). Similarly, poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromer was synthesized by reacting ultra-low molecular weight poly(L: -lactide) (ULMW PLA) and PEG with FuCl. The blend PLGF/PLEOF and PLAF/PLEOF macromers were self-assembled into NPs by dialysis. The NPs were characterized with respect to particle size distribution, morphology, and loading efficiency. The physical state and miscibility of Paclitaxel in NPs were characterized by differential scanning calorimetry. Tumor cell uptake and cytotoxicity of Paclitaxel loaded NPs were measured by incubation with HCT116 human colon carcinoma cells. The distribution of NPs in vivo was assessed with Apc(Min/+)mouse using infrared imaging. PLEOF macromer, due to its amphiphilic nature, acted as a surface active agent in the process of self-assembly which produced core-shell NPs with PLGF/PLAF and PLEOF macromers as the core and shell, respectively. The encapsulation efficiency ranged from 70 to 56% and it was independent of the macromer but decreased with increasing concentration of Paclitaxel. Most of the PLGF and PLAF NPs degraded in 15 and 28 days, respectively, which demonstrated that the release was dominated by hydrolytic degradation and erosion of the matrix. As the concentration of Paclitaxel was increased from 0 to 10, and 40 mug/ml, the viability of HCT116 cells incubated with free Paclitaxel decreased from 100 to 65 and 40%, respectively, while those encapsulated in PLGF/PLEOF NPs decreased from 93 to 54 and 28%. Groups with Paclitaxel loaded NPs had higher cytotoxicity compared to

  15. A randomised controlled trial comparing the effect of adjuvant ...

    African Journals Online (AJOL)

    Background: Intrathecal adjuvants are added to local anaesthetics to improve the quality of neuraxial blockade and prolong the duration of analgesia during spinal anaesthesia. Used intrathecally, fentanyl improves the quality of spinal blockade as compared to plain bupivacaine and confers a short duration of post ...

  16. Clinical trial comparing excision and primary closure with modified ...

    African Journals Online (AJOL)

    Walid Galal Elshazly

    2011-12-03

    Dec 3, 2011 ... sure, advancement flap (Karydakis procedure), local advance- ment flap (V-Y advancement flap), and rotational flap. (Limberg flap, modified Limberg flap, gluteus maximus myo- cutaneous flap).5,6. However, there have been few clinical studies to compare the rhomboid fasciocutaneous transposition flap ...

  17. Clinical trial comparing excision and primary closure with modified ...

    African Journals Online (AJOL)

    The aim of this study was to compare modified Limberg flap procedure with excision and primary closure in the treatment of uncomplicated pilonidal disease. Methods: This study was conducted on 120 patients with uncomplicated sacrococcygeal pilonidal disease that were randomly allocated into two groups: group I ...

  18. Pain Relief in Labor: A Randomized Controlled Trial Comparing ...

    African Journals Online (AJOL)

    Conclusions: This study showed that 600 mg intramuscular paracetamol provides similar and modest pain relief in labor when compared to 100 mg intramuscular tramadol. It also has fewer maternal adverse effects and favorable neonatal outcome such as tramadol. It is concluded that intramuscular paracetamol is simple, ...

  19. PRIVATE MANUFACTURERS’ THRESHOLDS TO INVEST IN COMPARATIVE EFFECTIVENESS TRIALS

    OpenAIRE

    Basu, Anirban; Meltzer, David

    2012-01-01

    The recent rush of enthusiasm for public investment in comparative effectiveness research (CER) in the United States has focused attention on these public investments. However, little attention has been given to how changing public investment in CER may affect private manufacturers’ incentives for CER, which has long been a major source of CER. In this work, based on a simple revenue maximizing economic framework, we generate predictions on thresholds to invest in CER for a private manufactur...

  20. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial.

    Science.gov (United States)

    Swain, Sandra M; Tang, Gong; Geyer, Charles E; Rastogi, Priya; Atkins, James N; Donnellan, Paul P; Fehrenbacher, Louis; Azar, Catherine A; Robidoux, André; Polikoff, Jonathan A; Brufsky, Adam M; Biggs, David D; Levine, Edward A; Zapas, John L; Provencher, Louise; Northfelt, Donald W; Paik, Soonmyung; Costantino, Joseph P; Mamounas, Eleftherios P; Wolmark, Norman

    2013-09-10

    Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.

  1. The efficacy of maggot debridement therapy - a review of comparative clinical trials

    DEFF Research Database (Denmark)

    Zarchi, K.; Jemec, G.B.

    2012-01-01

    in a variety of ulcers. However, comparative clinical trials and in particular randomized controlled trials investigating the efficacy of MDT are sparse. A systematic search in the literature showed three randomized clinical trials and five non randomized studies evaluating the efficacy of sterile Lucilia......, including hydrocolloid, hydrogel and saline moistened gauze. However, the design of the studies was suboptimal, with important differences in the use of other therapies, such as compression, that may influence both debridement and healing between the compared groups, as well as inappropriately short follow...

  2. Trial of Labor Compared With Cesarean Delivery in Superobese Women.

    Science.gov (United States)

    Grasch, Jennifer L; Thompson, Jennifer L; Newton, J Michael; Zhai, Amy W; Osmundson, Sarah S

    2017-11-01

    To examine whether labor compared with planned cesarean delivery is associated with increased maternal and neonatal morbidity. We conducted a retrospective cohort study of all women with body mass indexes (BMIs) at delivery of 50 or greater delivering a live fetus at 34 weeks of gestation of greater between January 1, 2008, and December 31, 2015. Pregnancies with multiple gestations and major fetal anomalies were excluded. The primary outcome was a composite of maternal and neonatal morbidity and was estimated to be 50% in superobese women based on institutional data. A sample size of 338 women determined the study period and was selected to show a 30% difference in the incidence of the primary outcome between the two groups. Multivariate logistic regression adjusted for potential confounders. There were 344 women with BMIs of 50 or greater who met eligibility criteria, of whom 201 (58%) labored and 143 (42%) underwent planned cesarean delivery. Women who labored were younger, more likely to be nulliparous, and less likely to have pre-existing diabetes. Among women who labored, 45% underwent a cesarean delivery, most commonly for labor arrest (61%) or nonreassuring fetal status (28%). Composite maternal and neonatal morbidity was reduced among women who labored even after adjusting for age, parity, pre-existing diabetes, and prior cesarean delivery (adjusted odds ratio 0.42, 95% CI 0.24-0.75). In the subgroup of women (n=234) who underwent a cesarean delivery, whether planned (n=143) or after labor (n=91), there were no differences in maternal and neonatal morbidity except that severe maternal morbidity was increased in women (n=12) who labored (8.8% compared with 2.1%, relative risk 4.2, 95% CI 1.14-15.4). Despite high rates of cesarean delivery in women with superobesity, labor is associated with lower composite maternal and neonatal morbidity. Severe maternal morbidity may be higher in women who require a cesarean delivery after labor.

  3. The decision to conduct a head-to-head comparative trial: a game-theoretic analysis.

    Science.gov (United States)

    Mansley, Edward C; Elbasha, Elamin H; Teutsch, Steven M; Berger, Marc L

    2007-01-01

    Recent Medicare legislation calls on the Agency for Healthcare Research and Quality to conduct research related to the comparative effectiveness of health care items and services, including prescription drugs. This reinforces earlier calls for head-to-head comparative trials of clinically relevant treatment alternatives. Using a game-theoretic model, the authors explore the decision of pharmaceutical companies to conduct such trials. The model suggests that an important factor affecting this decision is the potential loss in market share and profits following a result of inferiority or comparability. This hidden cost is higher for the market leader than the market follower, making it less likely that the leader will choose to conduct a trial. The model also suggests that in a full-information environment, it will never be the case that both firms choose to conduct such a trial. Furthermore, if market shares and the probability of proving superiority are similar for both firms, it is quite possible that neither firm will choose to conduct a trial. Finally, the results indicate that incentives that offset the direct cost of a trial can prevent a no-trial equilibrium, even when both firms face the possibility of an inferior outcome.

  4. Randomized Controlled Trial Comparing Daycare and Overnight Stay Laparoscopic Cholecystectomy.

    Science.gov (United States)

    Salleh, A A M; Affirul, C A; Hairol, O; Zamri, Z; Azlanudin, A; Hilmi, M A; Razman, J

    2015-01-01

    This present study sought to review the feasibility and patients' satisfaction of laparoscopic cholecystectomy to be perform as daycare procedure. Sixty-two patients with symptomatic gallstones were recruited within a year. They were randomized into overnight stay and daycare groups. The outcomes and post-operative complications were analyzed. Fifty-eight patients were eligible for analysis and four patients were excluded because of conversion to open cholecystectomy. All patients in daycare group reported no fever but two patients in the overnight stay group complaint of post-operative fever (p=0.150). The mean pain score using Visual Analogue Score (VAS) in daycare group was 2.93 but in the overnight stay was recorded as 3.59 (p=0.98). Five patients had post-operative nausea and vomiting (PONV) in daycare group compared to 2 patients in the overnight stay group (p=0.227). Patient's satisfaction were higher in the daycare group (p=0.160). All patients in daycare group were back at work within a week but in overnight stay, 11 patients had to stay off work for more than one week (p=0.01). Daycare laparoscopic cholecystectomy is safe and feasible. The satisfaction of daycare surgery is higher than overnight stay group. Patients' selection is an important aspect of its success.

  5. High response rates following paclitaxel/5-FU and simultaneous radiotherapy in advanced head and neck carcinoma; Hohe Remissionsraten unter simultaner Radio- und Chemotherapie mit Paclitaxel/5-FU in der Behandlung fortgeschrittener Kopf-Hals-Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, M.; Westerhausen, M. [St.-Johannes-Hospital, Duisburg (Germany). Medizinische Klinik II; Makoski, H.B. [Staedtische Kliniken, Duisburg (Germany). Radioonkologie; Sesterhenn, K. [St. Anna-Krankenhaus, Duisburg (Germany). HNO-Klinik; Schroeder, R. [Bristol Myers Squibb, Muenchen (Germany). Dept. of Oncology

    1997-11-01

    The main stay of treatment for head and neck cancer patients with advanced disease has been chemotherapy with Cisplatin/5-FU and simultaneous applied radiotherapy. With this multimodality treatment including radical surgery after two cycles of neoadjuvant chemotherapy and 40 Gy radiotherapy we reported 60% complete remission after 5 years for patients with stage III/IV of head and neck cancer. Paclitaxel, a new plant product, has demonstrated significant antineoplastic activity in head and neck tumors (ECOG-Study: 40% RR). Therefore we performed a trial with Taxol/5-FU and simultaneous radiation in a neoadjuvant and postoperative adjuvant setting of stage III/IV squamous cell carcinoma of the head and neck with pre-existent contraindication against Cisplatin. Patients and Methods: 30 patients with a primarily inoperable stage III/IV of SCC of the head and neck were enrolled to receive day 1 and 29 Taxol 175 mg/m{sup 2} as a 3-hour-infusion, followed by 120-hour-cvi of 1000 mg/m{sup 2}/d 5-FU. Locally irradiation was given ad 40 Gy (2 Gy/d/day 1-26). Radical surgery followed about day 56. Postoperatively patients received again 2 cycles of Taxol/5-FU and simultaneous irradiation with 30 Gy. Results: So far 30 patients were treated and all patients reached a CR after complete treatment, ongoing for 23/30 patients for 6 till 34 months: 4 patients developed a second neoplasia, and 3 patients gloved a local relapse. The principal toxicity was moderate (neutropenia, peripheral neuropathy, arthralgia/myalgia) and sensible with supportive care (e.g. PEG). Conclusions: The results suggest that the treatment of SCC of the head and neck with Taxol/5-FU and simultaneous radiation and radical surgery is a highly effective schedule and comparable with the treatment with Cisplatin/5-FU. (orig.) [Deutsch] Der Standard in der Behandlung weit forgeschrittener, primaer inoperabler Kopf-Hals-Tumoren stellte die Cisplatinhaltige Chemotherapiekombination mit 5-FU dar mit simultan

  6. Patient-reported (EORTC QLQ-CIPN20) versus physician-reported (CTCAE) quantification of oxaliplatin- and paclitaxel/carboplatin-induced peripheral neuropathy in NCCTG/Alliance clinical trials

    NARCIS (Netherlands)

    Le-Rademacher, J.; Kanwar, R.; Seisler, D.; Pachman, D.R.; Qin, R.; Abyzov, A.; Ruddy, K.J.; Banck, M.S.; Lavoie Smith, E.M.; Dorsey, S.G.; Aaronson, N.K.; Sloan, J.; Loprinzi, C.L.; Beutler, A.S.

    2017-01-01

    PURPOSE: Clinical practice guidelines on chemotherapy-induced peripheral neuropathy (CIPN) use the NCI Common Terminology Criteria for Adverse Events (CTCAE), while recent clinical trials employ a potentially superior measure, the European Organization for Research and Treatment of Cancer Quality of

  7. A randomized phase II study of carboplatin with weekly or every-3-week nanoparticle albumin-bound paclitaxel (abraxane) in patients with extensive-stage small cell lung cancer.

    Science.gov (United States)

    Grilley-Olson, Juneko E; Keedy, Vicki L; Sandler, Alan; Moore, Dominic T; Socinski, Mark A; Stinchcombe, Thomas E

    2015-02-01

    Platinum plus etoposide is the standard therapy for extensive-stage small cell lung cancer (ES-SCLC) and is associated with significant myelosuppression. We hypothesized that the combination of carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) would be better tolerated. We investigated carboplatin with nab-paclitaxel on every-3-week and weekly schedules. This noncomparative randomized phase II trial used a two-stage design. The primary objective was objective response rate, and secondary objectives were progression-free survival, overall survival, and toxicity. Patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status ≤2 and no prior chemotherapy were randomized in a 1:1 ratio to arm A (carboplatin area under the curve [AUC] of 6 on day 1 and nab-paclitaxel of 300 mg/m(2) on day 1 every 3 weeks) or arm B (carboplatin AUC of 6 on day 1 and nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15 every 21 days). Response was assessed after every two cycles. Patients required frequent dose reductions, treatment delays, and omission of the weekly therapy. The trial was closed because of slow accrual. Carboplatin and nab-paclitaxel demonstrated activity in ES-SCLC but required frequent dose adjustments. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

  8. Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Xiao W

    2012-03-01

    Full Text Available Wenwu Xiao1, Juntao Luo2, Teesta Jain3, John Riggs3, Harry P Tseng1, Paul T Henderson3, Simon R Cherry4, Douglas Rowland4, Kit S Lam1,31Department of Biochemistry and Molecular Medicine, UC Davis Cancer Center, University of California Davis, Sacramento, CA; 2Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY; 3Department of Internal Medicine, Division of Hematology and Oncology, 4Department of Biomedical Engineering, UC Davis Cancer Center, University of California Davis, Davis, CABackground: A multifunctional telodendrimer-based micelle system was characterized for delivery of imaging and chemotherapy agents to mouse tumor xenografts. Previous optical imaging studies demonstrated qualitatively that these classes of nanoparticles, called nanomicelles, preferentially accumulate at tumor sites in mice. The research reported herein describes the detailed quantitative imaging and biodistribution profiling of nanomicelles loaded with a cargo of paclitaxel.Methods: The telodendrimer was covalently labeled with 125I and the nanomicelles were loaded with 14C-paclitaxel, which allowed measurement of pharmacokinetics and biodistribution in the mice using microSPECT/CT imaging and liquid scintillation counting, respectively.Results: The radio imaging data showed preferential accumulation of nanomicelles at the tumor site along with a slower clearance rate than paclitaxel formulated in Cremophor EL (Taxol®. Liquid scintillation counting confirmed that 14C-labeled paclitaxel sequestered in nanomicelles had increased uptake by tumor tissue and slower pharmacokinetics than Taxol.Conclusion: Overall, the results indicate that nanomicelle-formulated paclitaxel is a potentially superior formulation compared with Taxol in terms of water solubility, pharmacokinetics, and tumor accumulation, and may be clinically useful for both tumor imaging and improved chemotherapy applications

  9. A mucoadhesive in situ gel delivery system for paclitaxel.

    Science.gov (United States)

    Jauhari, Saurabh; Dash, Alekha K

    2006-06-02

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% +/- 0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/- 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.

  10. First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig enhances immune responses and antitumor activity

    Directory of Open Access Journals (Sweden)

    Gligorov Joseph

    2010-07-01

    Full Text Available Abstract Background IMP321 is a recombinant soluble LAG-3Ig fusion protein that binds to MHC class II with high avidity and mediates APC and then antigen-experienced memory CD8+ T cell activation. We report clinical and biological results of a phase I/II in patients with metastatic breast carcinoma (MBC receiving first-line paclitaxel weekly, 3 weeks out of 4. Methods MBC patients were administered one dose of IMP321 s.c. every two weeks for a total of 24 weeks (12 injections. The repeated single doses were administered the day after chemotherapy at D2 and D16 of the 28-day cycles of paclitaxel (80 mg/m2 at D1, D8 and D15, for 6 cycles. Blood samples were taken 13 days after the sixth and the twelfth IMP321 injections to determine sustained APC, NK and memory CD8 T cell responses. Results Thirty MBC patients received IMP321 in three cohorts (doses: 0.25, 1.25 and 6.25 mg. IMP321 induced both a sustained increase in the number and activation of APC (monocytes and dendritic cells and an increase in the percentage of NK and long-lived cytotoxic effector-memory CD8 T cells. Clinical benefit was observed for 90% of patients with only 3 progressors at 6 months. Also, the objective tumor response rate of 50% compared favorably to the 25% rate reported in the historical control group. Conclusions The absence of toxicity and the demonstration of activity strongly support the future development of this agent for clinical use in combined first-line regimens. Trial registration ClinicalTrials.gov NCT00349934

  11. A randomized phase II study of carboplatin plus pegylated liposomal doxorubicin versus carboplatin plus paclitaxel in platinum sensitive ovarian cancer patients: a Hellenic Cooperative Oncology Group study

    Directory of Open Access Journals (Sweden)

    Briasoulis Evangelos

    2010-01-01

    Full Text Available Abstract Background Platinum-based combinations are the standard second-line treatment for platinum-sensitive ovarian cancer (OC. This randomized phase II study was undertaken in order to compare the combination of carboplatin and pegylated liposomal doxorubicin (LD with carboplatin and paclitaxel (CP in this setting. Methods Patients with histologically confirmed recurrent OC, at the time of or more than 6 months after platinum-based chemotherapy, were randomized to six cycles of CP (carboplatin AUC5 + paclitaxel 175 mg/m2, d1q21 or CLD (carboplatin AUC5 + pegylated LD 45 mg/m2, d1q28. Results A total of 189 eligible patients (CP 96, CLD 93, with a median age of 63 years, median Performance Status (PS 0 and a median platinum free interval (PFI of 16.5 months, entered the study. Discontinuation due to toxicity was higher in the CP patients (13.5% versus 3%, P = 0.016. The overall response rate was similar: CP 58% versus CLD 51%, P = 0.309 (Complete Response; CR 34% versus 23% and there was no statistical difference in time-to-progression (TTP or overall survival (OS; TTP 10.8 months CP versus 11.8 CLD, P = 0.904; OS 29.4 months CP versus 24.7 CLD, P = 0.454. No toxic deaths were recorded. Neutropenia was the most commonly seen severe toxicity (CP 30% versus CLD 35%. More frequent in CLD were severe thrombocytopenia (11% versus 2%, P = 0.016, skin toxicity and Palmar-plantar erythrodysesthesia (PPE grade 1-2 (38% versus 9%, PP = 0.029, 20% versus 5%, P = 0.003. PS and PFI were independent prognostic factors for TTP and OS. Conclusions The combination of pegylated LD with carboplatin is effective, showing less neurotoxicity and alopecia than paclitaxel-carboplatin. It thus warrants a further phase III evaluation as an alternative treatment option for platinum-sensitive OC patients. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12609000436279

  12. Paclitaxel-Based Chemoradiotherapy in the Treatment of Patients With Operable Esophageal Cancer

    International Nuclear Information System (INIS)

    Kelsey, Chris R.; Chino, Junzo P.; Willett, Christopher G.; Clough, Robert W.; Hurwitz, Herbert I.; Morse, Michael A.; Bendell, Johanna C.; D'Amico, Thomas A.; Czito, Brian G.

    2007-01-01

    Purpose: To compare a neoadjuvant regimen of cisplatin/5-fluorouracil (5-FU) and concurrent radiation therapy (RT) with paclitaxel-based regimens and RT in the management of operable esophageal (EC)/gastroesophageal junction (GEJ) cancer. Methods and Materials: All patients receiving neoadjuvant chemotherapy (CT) and RT for EC/GEJ cancer at Duke University between January 1995 and December 2004 were included. Clinical end points were compared for patients receiving paclitaxel-based regimens (TAX) vs. alternative regimens (non-TAX). Local control (LC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Chi-square analysis was performed to test the effect of TAX on pathologic complete response (pCR) rates and toxicity. Results: A total of 109 patients received CT-RT followed by esophagectomy (95 M; 14 F). Median RT dose was 45 Gy (range, 36-66 Gy). The TAX and non-TAX groups comprised 47% and 53% of patients, respectively. Most (83%) TAX patients received three drug regimens including platinum and a fluoropyrimidine. In the non-TAX group, 89% of the patients received cisplatin and 5-FU. The remainder received 5-FU or capecitabine alone. Grade 3-4 toxicity occurred in 41% of patients receiving TAX vs. 24% of those receiving non-TAX (p = 0.19). Overall pCR rate was 39% (39% with TAX vs. 40% with non-TAX, p = 0.9). Overall LC, DFS, and OS at 3 years were 80%, 34%, and 37%, respectively. At 3 years, there were no differences in LC (75% vs. 85%, p = 0.33) or OS (37% vs. 37%, p = 0.32) between TAX and non-TAX groups. Conclusions: In this large experience, paclitaxel-containing regimens did not improve pCR rates or clinical end points compared to non-paclitaxel-containing regimens

  13. A Comparative Effectiveness Education Trial for Lifestyle Health Behavior Change in African Americans

    Science.gov (United States)

    Halbert, Chanita Hughes; Bellamy, Scarlett; Briggs, Vanessa; Delmoor, Ernestine; Purnell, Joseph; Rogers, Rodney; Weathers, Benita; Johnson, Jerry C.

    2017-01-01

    Obesity and excess weight are significant clinical and public health issues that disproportionately affect African Americans because of physical inactivity and unhealthy eating. We compared the effects of alternate behavioral interventions on obesity-related health behaviors. We conducted a comparative effectiveness education trial in a…

  14. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction

    NARCIS (Netherlands)

    M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert); F.J.J. van de Werf (Frans); P.W. Armstrong (Paul); P.E. Aylward (Philip Edmund); G.I. Barbash; E.R. Bates (Eric); A. Betriu; J.H. Chesebro (James); J.J. Col (Jacques); D.P. de Bono (David); J.M. Gore (Joel); A.D. Guerci (Alan); J.R. Hampton (John)

    1993-01-01

    textabstractBACKGROUND: The relative efficacy of streptokinase and tissue plasminogen activator and the roles of intravenous as compared with subcutaneous heparin as adjunctive therapy in acute myocardial infarction are unresolved questions. The current trial was designed to compare new, aggressive

  15. Comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: a randomized trial

    Science.gov (United States)

    Background: Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. Objective: To compare Tai Chi with standard physical therapy f...

  16. Study of Paclitaxel-Treated HeLa Cells by Differential Electrical Impedance Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Julie Kirkegaard

    2014-08-01

    Full Text Available This work describes the electrical investigation of paclitaxel-treated HeLa cells using a custom-made microfluidic biosensor for whole cell analysis in continuous flow. We apply the method of differential electrical impedance spectroscopy to treated HeLa cells in order to elucidate the changes in electrical properties compared with non-treated cells. We found that our microfluidic system was able to distinguish between treated and non-treated cells. Furthermore, we utilize a model for electrical impedance spectroscopy in order to perform a theoretical study to clarify our results. This study focuses on investigating the changes in the electrical properties of the cell membrane caused by the effect of paclitaxel. We observe good agreement between the model and the obtained results. This establishes the proof-of-concept for the application in cell drug therapy.

  17. Using low-dose radiation to potentiate the effect of induction chemotherapy in head and neck cancer: Results of a prospective phase 2 trial

    Directory of Open Access Journals (Sweden)

    Susanne M. Arnold, MD

    2016-10-01

    Conclusion: Chemopotentiating LDFRT combined with paclitaxel and carboplatin is effective in SCCHN and provided an excellent median overall survival of 107.2 months, with median PFS not yet reached in this locally advanced SCCHN cohort. This compares favorably to prior investigations and caused fewer grade 3 and 4 toxicities than more intensive, 3-drug induction regimens. This trial demonstrates the innovative use of LDFRT as a potentiator of chemotherapy.

  18. Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation.

    Science.gov (United States)

    Wang, Hongbo; Cheng, Guang; Du, Yuan; Ye, Liang; Chen, Wenzhong; Zhang, Leiming; Wang, Tian; Tian, Jingwei; Fu, Fenghua

    2013-03-01

    The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these problems, we developed a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation, known as Lipusu. In this study, we performed in vitro and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with special regard to hypersensitivity reactions. First, Swiss mice were used to determine the lethal dosages, and then to evaluate hypersensitivity reactions, followed by histopathological examination and enzyme-linked immunosorbent assays (ELISAs) of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used to analyze in vitro complement activation. Finally, an MTT assay was used to determine the in vitro anti-proliferation activity. Our data clearly showed that Lipusu displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related lung lesions, which may be associated with the fact that Lipusu did not activate complement or increase histamine release in vivo. Moreover, Lipusu did not promote complement activation in healthy human serum in vitro, and demonstrated anti-proliferative activity against human cancer cells, similar to that of Taxol. Therefore, the improved formulation of paclitaxel, which exhibited a much better safety profile and comparable cytotoxic activity to Taxol, may bring a number of benefits to cancer patients.

  19. Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine-paclitaxel nanoconjugate

    Directory of Open Access Journals (Sweden)

    Sang Van

    2010-10-01

    Full Text Available Sang Van1, Sanjib K Das1, Xinghe Wang1, Zhongling Feng1, Yi Jin1, Zheng Hou1, Fu Chen1, Annie Pham1, Nan Jiang1, Stephen B Howell2, Lei Yu11Nitto Denko Technical Corporation, Oceanside, CA, USA; 2Moores Cancer Center, University of California, La Jolla, San Diego, CA, USAAbstract: The purpose of this study was to develop a novel, highly water-soluble poly(L-γ-glutamyl-glutamine-paclitaxel nanoconjugate (PGG-PTX that would improve the therapeutic index of paclitaxel (PTX. PGG-PTX is a modification of poly(L-glutamic acid-paclitaxel conjugate (PGA-PTX in which an additional glutamic acid has been added to each glutamic side chain in the polymer. PGG-PTX has higher water-solubility and faster dissolution than PGA-PTX. Unlike PGA-PTX, PGG-PTX self-assembles into nanoparticles, whose size remains in the range of 12–15 nm over the concentration range from 25 to 2,000 µg/mL in saline. Its critical micellar concentration in saline was found to be ~25 µg/mL. The potency of PGG-PTX when tested in vitro against the human lung cancer H460 cell line was comparable to other known polymer-PTX conjugates. However, PGG-PTX possesses lower toxicity compared with PGA-PTX in mice. The maximum tolerated dose of PGG-PTX was found to be 350 mg PTX/kg, which is 2.2-fold higher than the maximum tolerated dose of 160 mg PTX/kg reported for the PGA-PTX. This result indicates that PGG-PTX was substantially less toxic in vivo than PGA-PTX.Keywords: nanoconjugates, poly(L-glutamic acid, poly(L-γ-glutamyl-glutamine-paclitaxel, nanoparticles, anticancer

  20. Assessment of paclitaxel induced sensory polyneuropathy with "Catwalk" automated gait analysis in mice.

    Directory of Open Access Journals (Sweden)

    Petra Huehnchen

    Full Text Available Neuropathic pain as a symptom of sensory nerve damage is a frequent side effect of chemotherapy. The most common behavioral observation in animal models of chemotherapy induced polyneuropathy is the development of mechanical allodynia, which is quantified with von Frey filaments. The data from one study, however, cannot be easily compared with other studies owing to influences of environmental factors, inter-rater variability and differences in test paradigms. To overcome these limitations, automated quantitative gait analysis was proposed as an alternative, but its usefulness for assessing animals suffering from polyneuropathy has remained unclear. In the present study, we used a novel mouse model of paclitaxel induced polyneuropathy to compare results from electrophysiology and the von Frey method to gait alterations measured with the Catwalk test. To mimic recently improved clinical treatment strategies of gynecological malignancies, we established a mouse model of dose-dense paclitaxel therapy on the common C57Bl/6 background. In this model paclitaxel treated animals developed mechanical allodynia as well as reduced caudal sensory nerve action potential amplitudes indicative of a sensory polyneuropathy. Gait analysis with the Catwalk method detected distinct alterations of gait parameters in animals suffering from sensory neuropathy, revealing a minimized contact of the hind paws with the floor. Treatment of mechanical allodynia with gabapentin improved altered dynamic gait parameters. This study establishes a novel mouse model for investigating the side effects of dose-dense paclitaxel therapy and underlines the usefulness of automated gait analysis as an additional easy-to-use objective test for evaluating painful sensory polyneuropathy.

  1. Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction.

    Science.gov (United States)

    Lu, Yimin; Wang, Jun; Liu, Lei; Yu, Lequn; Zhao, Nian; Zhou, Xingju; Lu, Xudong

    2017-04-01

    Non-small-cell lung cancer is one of the most lethal cancers in the worldwide. Although Paclitaxel-based combinational therapies have long been used as a standard treatment in aggressive non-small-cell lung cancers, Paclitaxel resistance emerges as a major clinical problem. It has been demonstrated that Curcumin from Curcuma longa as a traditional Chinese medicine can inhibit cancer cell proliferation. However, the role of Curcumin in Paclitaxel-resistant non-small-cell lung cancer cells is not clear. In this study, we investigated the effect of Curcumin on the Paclitaxel-resistant non-small-cell lung cancer cells and found that Curcumin treatment markedly increased the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel. Mechanically, the study revealed that Curcumin could reduce the expression of metastasis-associated gene 1 (MTA1) gene through upregulation of microRNA-30c in Paclitaxel-resistant non-small-cell lung cancer cells. During the course, MTA1 reduction sensitized Paclitaxel-resistant non-small-cell lung cancer cells and enhanced the effect of Paclitaxel. Taken together, our studies indicate that Curcumin increases the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Curcumin might be a potential adjuvant for non-small-cell lung cancer patients during Paclitaxel treatment.

  2. Enhanced efficacy of combined {sup 213}Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Gilbertz, Klaus-Peter [German Armed Forces, Institute of Radiobiology, Munich (Germany); Baumgart, Anja [Technische Universitaet Muenchen, III. Medical Department, Munich (Germany); Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K. [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-12-15

    Targeted therapy with {alpha}-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the {alpha}-emitter {sup 213}Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined {sup 213}Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with {sup 213}Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined {sup 213}Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with {sup 213}Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 {mu}g) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with {sup 213}Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either {sup 213}Bi-DTPA-F3 or paclitaxel alone. Combined treatment with {sup 213}Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

  3. Enhanced efficacy of combined 213Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

    International Nuclear Information System (INIS)

    Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus; Gilbertz, Klaus-Peter; Baumgart, Anja; Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K.; Bruchertseifer, Frank; Morgenstern, Alfred

    2012-01-01

    Targeted therapy with α-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the α-emitter 213 Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined 213 Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either 213 Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with 213 Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined 213 Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either 213 Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with 213 Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 μg) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with 213 Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either 213 Bi-DTPA-F3 or paclitaxel alone. Combined treatment with 213 Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

  4. Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner

    Directory of Open Access Journals (Sweden)

    Taylor RM

    2012-08-01

    Full Text Available Robert M Taylor,1,2 Laurel O Sillerud1,31Department of Biochemistry and Molecular Biology, 2New Mexico Cancer Nanoscience and Microsystems Training Center, 3UNM Cancer Center, University of New Mexico, Albuquerque, NM, USABackground and methods: Problems with the clinical management of prostate cancer include the lack of both specific detection and efficient therapeutic intervention. We report the encapsulation of superparamagnetic iron platinum nanoparticles (SIPPs and paclitaxel in a mixture of polyethyleneglycolated, fluorescent, and biotin-functionalized phospholipids to create multifunctional SIPP-PTX micelles (SPMs that were conjugated to an antibody against prostate-specific membrane antigen (PSMA for the specific targeting, magnetic resonance imaging (MRI, and treatment of human prostate cancer xenografts in mice.Results: SPMs were 45.4 ± 24.9 nm in diameter and composed of 160.7 ± 22.9 µg/mL iron, 247.0 ± 33.4 µg/mL platinum, and 702.6 ± 206.0 µg/mL paclitaxel. Drug release measurements showed that, at 37°C, half of the paclitaxel was released in 30.2 hours in serum and two times faster in saline. Binding assays suggested that PSMA-targeted SPMs specifically bound to C4-2 human prostate cancer cells in vitro and released paclitaxel into the cells. In vitro, paclitaxel was 2.2 and 1.6 times more cytotoxic than SPMs to C4-2 cells at 24 and 48 hours of incubation, respectively. After 72 hours of incubation, paclitaxel and SPMs were equally cytotoxic. SPMs had MRI transverse relaxivities of 389 ± 15.5 Hz/mM iron, and SIPP micelles with and without drug caused MRI contrast enhancement in vivo.Conclusion: Only PSMA-targeted SPMs and paclitaxel significantly prevented growth of C4-2 prostate cancer xenografts in nude mice. Furthermore, mice injected with PSMA-targeted SPMs showed significantly more paclitaxel and platinum in tumors, compared with nontargeted SPM-injected and paclitaxel-injected mice.Keywords: iron platinum, MRI

  5. Novel free paclitaxel-loaded poly(L-γ-glutamylglutamine–paclitaxel nanoparticles

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2011-01-01

    Full Text Available Danbo Yang1, Sang Van2, Xinguo Jiang3, Lei Yu1,21Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People's Republic of China; 2Biomedical Group, Nitto Denko Technical Corporation, Oceanside, CA, USA; 3School of Pharmacy, Fudan University, Shanghai, People's Republic of ChinaAbstract: The purpose of this study was to develop a novel formulation of paclitaxel (PTX that would improve its therapeutic index. Here, we combined a concept of polymer–PTX drug conjugate with a concept of polymeric micelle drug delivery to form novel free PTX-loaded poly(L-γ-glutamylglutamine (PGG–PTX conjugate nanoparticles. The significance of this drug formulation emphasizes the simplicity, novelty, and flexibility of the method of forming nanoparticles that contain free PTX and conjugated PTX in the same drug delivery system. The results of effectively inhibiting tumor growth in mouse models demonstrated the feasibility of the nanoparticle formulation. The versatility and potential of this dual PTX drug delivery system can be explored with different drugs for different indications. Novel and simple formulations of PTX-loaded PGG–PTX nanoparticles could have important implications in translational medicines.Keywords: paclitaxel, polymeric micelle, poly(L-γ-glutamylglutamine–paclitaxel, nanoconjugate, nanoparticles

  6. Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

    Science.gov (United States)

    Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

    2016-09-02

    To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.

  7. STX140, but not paclitaxel, inhibits mammary tumour initiation and progression in C3(1/SV40 T/t-antigen transgenic mice.

    Directory of Open Access Journals (Sweden)

    Florence Meyer-Losic

    Full Text Available Despite paclitxael's clinical success, treating hormone-refractory breast cancer remains challenging. Paclitaxel has a poor pharmacological profile, characterized by a low therapeutic index (TIX caused by severe dose limiting toxicities, such as neutropenia and peripheral neuropathy. Consequently, new drugs are urgently required. STX140, a compound previously shown to have excellent efficacy against many tumors, is here compared to paclitaxel in three translational in vivo breast cancer models, a rat model of peripheral neuropathy, and through pharmacological testing. Three different in vivo mouse models of breast cancer were used; the metastatic 4T1 orthotopic model, the C3(1/SV40 T-Ag model, and the MDA-MB-231 xenograft model. To determine TIX and pharmacological profile of STX140, a comprehensive dosing regime was performed in mice bearing MDA-MD-231 xenografts. Finally, peripheral neuropathy was examined using a rat plantar thermal hyperalgesia model. In the 4T1 metastatic model, STX140 and paclitaxel significantly inhibited primary tumor growth and lung metastases. All C3(1/SV40 T-Ag mice in the control and paclitaxel treated groups developed palpable mammary cancer. STX140 blocked 47% of tumors developing and significantly inhibited growth of tumors that did develop. STX140 treatment caused a significant (P<0.001 survival advantage for animals in early and late intervention groups. Conversely, in C3(1/SV40 T-Ag mice, paclitaxel failed to inhibit tumor growth and did not increase survival time. Furthermore, paclitaxel, but not STX140, induced significant peripheral neuropathy and neutropenia. These results show that STX140 has a greater anti-cancer efficacy, TIX, and reduced neurotoxicity compared to paclitaxel in C3(1/SV40 T-Ag mice and therefore may be of significant benefit to patients with breast cancer.

  8. Production of paclitaxel by Fusarium solani isolated from Taxus ...

    Indian Academy of Sciences (India)

    SEARCH U

    The mobile phase ... 0.1% trifluoroacetic acid (TFA) at a flow rate of 1 ml/min and absorbance was monitored at 227 nm. ... Institute of Microbial Technology, Chandigarh, India. ... engineering may improve paclitaxel production by F. solani.

  9. Preparation and evaluation of peptide-dendrimer-paclitaxel ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2017; 16 (4): 737-742 ... conjugates for treatment of heterogeneous stage 1 non- small cell lung ... Keywords: Paclitaxel, Lung cancer, Non-small cell lung cancer, Dendrimer, Peptide, PAMAM.

  10. Effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Yu-Lin Zhao

    2017-07-01

    Full Text Available Objective: To study the effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion. Methods: A total of 62 patients with esophageal cancer who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to random number table, with 31 cases in each group. Control group of patients received paclitaxel + cisplatin neoadjuvant chemotherapy + surgery, and observation group of patients accepted cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy + surgery. The differences in proliferation and invasion gene expression in the tumor tissue were compared between two groups of patients before and after chemotherapy. Results: Before chemotherapy, differences in proliferation and invasion gene expression in tumor tissue were not statistically significant between two groups of patients. After chemotherapy, proproliferation genes FOXA1, ABCE1, USP39 and Nestin mRNA expression in tumor tissue of observation group were significantly lower than those of control group; anti-proliferation genes PETN, KLF4, TSLC1 and AnnexinA2 mRNA expression were significantly higher than those of control group; pro-invasion genes γ-synuclein, CXCR4 and Snail mRNA expression were significantly lower than those of control group; anti-invasion genes CIAPIN1, Fez and Lrig1 mRNA expression were significantly higher than that of control group. Conclusions: Cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy can effectively inhibit the malignant degree of esophageal cancer cells and inhibit its proliferation and invasion.

  11. Synthesis and characterization of a fluorescent water-soluble paclitaxel prodrug.

    Science.gov (United States)

    Sohn, Jeong-Sun; Choi, Eun-Sun; Jo, Byung-Wook; Hess, Michael; Han, Song-Hee

    2010-05-01

    A fluorescence susceptible water-soluble paclitaxel was synthesized by a condensation reaction between PEGylated paclitaxel (namely, PP7) and 1-pyrene butyric acid (PBA) in order to obtain a better understanding of the mechanism of action of paclitaxel as well as of the environment of the paclitaxel-binding site. The reaction was performed successfully and the resulting paclitaxel was characterized by FT-NMR, analytical-HPLC, UV spectro photometry, and fluorescence spectrometry. The synthesized paclitaxel analogue showed a high susceptibility to fluorescence in both excitation and emission spectra. And we have investigated the time-resolved fluorescence behavior of them in different solvents and at different excitation wavelengths.

  12. Induction of apoptosis and cell proliferation inhibition by paclitaxel in ...

    African Journals Online (AJOL)

    In this study, anti-proliferative and apoptotic effects of paclitaxel, which is itself an antichemotherapeutic agent, to FM3A cell line originated from Mouse mammary carcinoma at 7 different doses were examined. Seven different doses of paclitaxel (P1 = 3 nM, P2 = 7.5 nM, P3 = 15 nM, P4 = 30 nM, P5 = 60 nM, P6 = 120 nM, ...

  13. A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).

    Science.gov (United States)

    Paajanen, Hannu; Grönroos, Juha M; Rautio, Tero; Nordström, Pia; Aarnio, Markku; Rantanen, Tuomo; Hurme, Saija; Dean, Kirsti; Jartti, Airi; Mecklin, Jukka-Pekka; Sand, Juhani; Salminen, Paulina

    2013-02-08

    Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial. The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point. The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting

  14. Economic evaluation of the randomized European Achalasia trial comparing pneumodilation with Laparoscopic Heller myotomy

    NARCIS (Netherlands)

    Moonen, A.; Busch, O.; Costantini, M.; Finotti, E.; Tack, J.; Salvador, R.; Boeckxstaens, G.; Zaninotto, G.

    2017-01-01

    BackgroundA recent multicenter randomized trial in achalasia patients has shown that pneumatic dilation resulted in equivalent relief of symptoms compared to laparoscopic Heller myotomy. Additionally, the cost of each treatment should be also taken in consideration. Therefore, the aim of the present

  15. Comparing surgical repair with conservative treatment for degenerative rotator cuff tears : a randomized controlled trial

    NARCIS (Netherlands)

    Lambers Heerspink, Okke; van Raay, Jos J. A. M.; Koorevaar, Rinco C. T.; van Eerden, Pepijn J. M.; Westerbeek, Robin E.; van 't Riet, Esther; van den Akker-Scheek, Inge; Diercks, Ronald L.

    Background: Good clinical results have been reported for both surgical and conservative treatment of rotator cuff tears. The primary aim of this randomized controlled trial was to compare functional and radiologic improvement after surgical and conservative treatment of degenerative rotator cuff

  16. High response rates following paclitaxel/5-FU and simultaneous radiotherapy in advanced head and neck carcinoma

    International Nuclear Information System (INIS)

    Schroeder, M.; Westerhausen, M.; Makoski, H.B.; Sesterhenn, K.; Schroeder, R.

    1997-01-01

    The main stay of treatment for head and neck cancer patients with advanced disease has been chemotherapy with Cisplatin/5-FU and simultaneous applied radiotherapy. With this multimodality treatment including radical surgery after two cycles of neoadjuvant chemotherapy and 40 Gy radiotherapy we reported 60% complete remission after 5 years for patients with stage III/IV of head and neck cancer. Paclitaxel, a new plant product, has demonstrated significant antineoplastic activity in head and neck tumors (ECOG-Study: 40% RR). Therefore we performed a trial with Taxol/5-FU and simultaneous radiation in a neoadjuvant and postoperative adjuvant setting of stage III/IV squamous cell carcinoma of the head and neck with pre-existent contraindication against Cisplatin. Patients and Methods: 30 patients with a primarily inoperable stage III/IV of SCC of the head and neck were enrolled to receive day 1 and 29 Taxol 175 mg/m 2 as a 3-hour-infusion, followed by 120-hour-cvi of 1000 mg/m 2 /d 5-FU. Locally irradiation was given ad 40 Gy (2 Gy/d/day 1-26). Radical surgery followed about day 56. Postoperatively patients received again 2 cycles of Taxol/5-FU and simultaneous irradiation with 30 Gy. Results: So far 30 patients were treated and all patients reached a CR after complete treatment, ongoing for 23/30 patients for 6 till 34 months: 4 patients developed a second neoplasia, and 3 patients gloved a local relapse. The principal toxicity was moderate (neutropenia, peripheral neuropathy, arthralgia/myalgia) and sensible with supportive care (e.g. PEG). Conclusions: The results suggest that the treatment of SCC of the head and neck with Taxol/5-FU and simultaneous radiation and radical surgery is a highly effective schedule and comparable with the treatment with Cisplatin/5-FU. (orig.) [de

  17. Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials.

    Directory of Open Access Journals (Sweden)

    Dimitrios K Matthaiou

    Full Text Available BACKGROUND: Neurocysticercosis, infection of the brain with larvae of Taenia solium (pork tapeworm, is one of several forms of human cysticercosis caused by this organism. We investigated the role of albendazole and praziquantel in the treatment of patients with parenchymal neurocysticercosis by performing a meta-analysis of comparative trials of their effectiveness and safety. METHODS AND PRINCIPAL FINDINGS: We performed a search in the PubMed database, Cochrane Database of Controlled Trials, and in references of relevant articles. Six studies were included in the meta-analysis. Albendazole was associated with better control of seizures than praziquantel in the pooled data analysis, when the generic inverse variance method was used to combine the incidence of seizure control in the included trials (patients without seizures/[patients x years at risk] (156 patients in 4 studies, point effect estimate [incidence rate ratio] = 4.94, 95% confidence interval 2.45-9.98. In addition, albendazole was associated with better effectiveness than praziquantel in the total disappearance of cysts (335 patients in 6 studies, random effects model, OR = 2.30, 95% CI 1.06-5.00. There was no difference between albendazole and praziquantel in reduction of cysts, proportion of patients with adverse events, and development of intracranial hypertension due to the administered therapy. CONCLUSIONS: A critical review of the available data from comparative trials suggests that albendazole is more effective than praziquantel regarding clinically important outcomes in patients with neurocysticercosis. Nevertheless, given the relative scarcity of trials, more comparative interventional studies--especially randomized controlled trials--are required to draw a safe conclusion about the best regimen for the treatment of patients with parenchymal neurocysticercosis.

  18. Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

    Science.gov (United States)

    Saito, Shota; Muneoka, Yusuke; Ishikawa, Takashi; Akazawa, Kouhei

    2017-12-01

    The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival

  19. Rosemary oil vs minoxidil 2% for the treatment of androgenetic alopecia: a randomized comparative trial.

    Science.gov (United States)

    Panahi, Yunes; Taghizadeh, Mohsen; Marzony, Eisa Tahmasbpour; Sahebkar, Amirhossein

    2015-01-01

    Rosmarinus officinalis L. is a medicinal plant with diverse activities including enhancement microcapillary perfusion. The present study aimed to investigate the clinical efficacy of rosemary oil in the treatment of androgenetic alopecia (AGA) and compare its effects with minoxidil 2%. Patients with AGA were randomly assigned to rosemary oil (n = 50) or minoxidil 2% (n = 50) for a period of 6 months. After a baseline visit, patients returned to the clinic for efficacy and safety evaluations every 3 months. A standardized professional microphotographic assessment of each volunteer was taken at the initial interview and after 3 and 6 months of the trial. No significant change was observed in the mean hair count at the 3-month endpoint, neither in the rosemary nor in the minoxidil group (P > .05). In contrast, both groups experienced a significant increase in hair count at the 6-month endpoint compared with the baseline and 3-month endpoint (P .05). The frequencies of dry hair, greasy hair, and dandruff were not found to be significantly different from baseline at either month 3 or month 6 trial in the groups (P > .05). The frequency of scalp itching at the 3- and 6-month trial points was significantly higher compared with baseline in both groups (P minoxidil group at both assessed endpoints (P < .05). The findings of the present trial provided evidence with respect to the efficacy of rosemary oil in the treatment of AGA.

  20. Weekly nanoparticle albumin bound-paclitaxel in combination with cisplatin versus weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese patients with advanced esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang HY

    2016-09-01

    Full Text Available Hai-ying Wang, Zhi-hua Yao, Hong Tang, Yan Zhao, Xiao-san Zhang, Shu-na Yao, Shu-jun Yang, Yan-yan Liu Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China Objective: More effective regimens for advanced esophageal squamous cell carcinoma (ESCC are urgently needed. Therefore, a retrospective study concerning the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin (nab-TP versus solvent-based paclitaxel plus cisplatin (sb-TP as a first-line therapy was conducted in Chinese patients with advanced ESCC.Methods: From June 2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2 on the first and eighth days (30 minutes infusion and cisplatin (75 mg/m2 on the second day every 21 days (nab-TP arm. Also, 43 patients were treated with solvent-based paclitaxel (80 mg/m2 intravenously on the first and eighth days and the same dose of cisplatin (sb-TP arm. The two groups were compared in terms of objective response rate (ORR, disease control rate, progression-free survival (PFS, overall survival (OS, and safety profile. OS and PFS were estimated using Kaplan–Meier methods to determine associations between chemotherapy regimens and survival outcomes.Results: Nab-TP demonstrated a higher ORR (50% vs 30%; P=0.082 and disease control rate (81% vs 65%; P=0.124 than sb-TP. Median OS was similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269. However, nab-TP resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3–6.9] than sb-TP (5.0 months [95% confidence interval: 4.4–5.6] (P=0.029. The most common adverse events included anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia in both the groups and no statistically significant differences were observed between the groups. With statistically significant differences, significantly less grade ≥3 peripheral neuropathy

  1. Paclitaxel-Fe3O4 nanoparticles inhibit growth of CD138–  CD34– tumor stem-like cells in multiple myeloma-bearing mice

    Directory of Open Access Journals (Sweden)

    Yang C

    2013-04-01

    Full Text Available Cuiping Yang,1,3,* Jing Wang,2,* Dengyu Chen,1,* Junsong Chen,1 Fei Xiong,4 Hongyi Zhang,1 Yunxia Zhang,2 Ning Gu,4 Jun Dou11Department of Pathogenic Biology and Immunology, Medical School, 2Department of Gynecology and Obstetrics, Zhongda Hospital, Southeast University, Nanjing, 3Department of Pathogenic Biology and Immunology, School of Basic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 4School of Biological Science and Medical Engineering, Southeast University, Nanjing, People’s Republic of China*These authors contributed equally to this workBackground: There is growing evidence that CD138– CD34– cells may actually be tumor stem cells responsible for initiation and relapse of multiple myeloma. However, effective drugs targeted at CD138– CD34– tumor stem cells are yet to be developed. The purpose of this study was to investigate the inhibitory effect of paclitaxel-loaded Fe3O4 nanoparticles (PTX-NPs on CD138– CD34– tumor stem cells in multiple myeloma-bearing mice.Methods: CD138– CD34– cells were isolated from a human U266 multiple myeloma cell line using an immune magnetic bead sorting method and then subcutaneously injected into mice with nonobese diabetic/severe combined immunodeficiency to develop a multiple myeloma-bearing mouse model. The mice were treated with Fe3O4 nanoparticles 2 mg/kg, paclitaxel 4.8 mg/kg, and PTX-NPs 0.64 mg/kg for 2 weeks. Tumor growth, pathological changes, serum and urinary interleukin-6 levels, and molecular expression of caspase-3, caspase-8, and caspase-9 were evaluated.Results: CD138– CD34– cells were found to have tumor stem cell characteristics. All the mice developed tumors in 40 days after injection of 1 × 106 CD138– CD34– tumor stem cells. Tumor growth in mice treated with PTX-NPs was significantly inhibited compared with the controls (P <  0.005, and the groups that received nanoparticles alone (P < 0.005 or paclitaxel alone (P < 0.05. In addition

  2. 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.

  3. Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer.

    Science.gov (United States)

    Pérez, Juan E; Machiavelli, Mario R; Romero, Alberto O; Romero Acuña, Luis A; Domínguez, María E; Fasce, Hebe; Flores Acosta, Luis; Marrone, Nora; Romero Acuña, Juan M; Langhi, Mario J; Amato, Sonia; Bologna, Fabrina; Ortiz, Eduardo H; Leone, Bernardo A; Lacava, Juan A; Vallejo, Carlos T

    2002-08-01

    A phase II trial was performed to evaluate the efficacy and toxicity of the novel combination of vinorelbine and paclitaxel as first-line chemotherapy in patients with stages IIIB and IV non-small-cell lung cancer. From January 1997 to September 1999, 34 patients (9 stage IIIB and 25 stage IV) received a regimen consisting of the following: vinorelbine 30 mg/m2 20 minutes intravenous (i.v.) infusion, days 1 and 8; and paclitaxel 135 mg/m2 3-hour i.v. (starting 1 hour after vinorelbine) on day 1. Cycles were repeated every 28 days until progression of disease or unacceptable toxicity development. The median age was 57 years (range 41-70 years); median performance status was 1. Histology was as follows: squamous cell in 24 (71%), large cell in 1 (3%), and adenocarcinoma in 9 (26%). All patients are evaluable for toxicity, whereas 30 are evaluable for response (4 patients refused treatment). Objective response was recorded in 4 of 30 patients (13%, 95% CI 1-25%). No complete response was observed. Partial response was recorded in 4 patients (13%), no change in 10 patients (34%), and progressive disease in 16 patients (53%). The median time to treatment failure was 4 months and median survival was 9 months. The limiting toxicity was myelosuppression: leukopenia in 23 patients (68%), whereas neutropenia was observed in 25 patients (78%). Peripheral neurotoxicity developed in 14 patients (41%) (without G3 or G4 episodes), and constipation (G1-G2: 10 patients), myalgia (G1-G2: 11 patients), diarrhea (G1-G2: 7 patients), and stomatitis were observed in 7 patients. Vinorelbine-paclitaxel combination showed only modest activity against locoregionally advanced or metastatic NSCLC.

  4. Anti-cancer, pharmacokinetic and biodistribution studies of cremophor el free alternative paclitaxel formulation.

    Science.gov (United States)

    Jain, Subheet K; Utreja, Puneet; Tiwary, Ashok K; Mahajan, Mohit; Kumar, Nikhil; Roy, Partha

    2014-01-01

    The aim of the present investigation is to determine the in vivo potential of previously developed and optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX formulation in comparison to marketed paclitaxel formulation. Intracellular uptake of CF-PTX was studied using A549 cells by fluorescence activated cell sorting assay (FACS) and fluorescence microscopy. In vivo anti-cancer activity of CF-PTX was evaluated using Ehrlich ascites carcinoma (EAC) model in mice followed by biodistribution and pharmacokinetic studies. FACS investigation showed that fluorescence marker acridine orange (AO) solution showed only 19.8±1.1% intracellular uptake where as significantly higher uptake was observed in the case of AO loaded CF-PTX formulation (85.4±2.3%). The percentage reduction in tumor volume for CF-PTX (72.5±2.3%) in EAC bearing mice was found to be significantly (p<0.05) higher than marketed formulation (58.6±2.8%) on 14th day of treatment. Pharmacokinetic and biodistribution studies showed sustained plasma concentration of paclitaxel depicted by higher mean residence time (MRT; 18.2±1.8 h) and elimination half life (12.8±0.6 h) with CF-PTX formulation as compared to marketed formulation which showed 4.4±0.2 h MRT and 3.6±0.4 h half life. The results of the present study demonstrated better in vivo performance of CF-PTX and this formulation appears to be a promising carrier for sustained and targeted delivery of paclitaxel.

  5. Vasodilatation in the rat dorsal hindpaw induced by activation of sensory neurons is reduced by Paclitaxel

    OpenAIRE

    Gracias, N.G.; Cummins, T.R.; Kelley, M.R.; Basile, D.P.; Iqbal, T.; Vasko, M.R.

    2010-01-01

    Peripheral neuropathy is a major side effect following treatment with the cancer chemotherapeutic drug paclitaxel. Whether paclitaxel-induced peripheral neuropathy is secondary to altered function of small diameter sensory neurons remains controversial. To ascertain whether the function of the small diameter sensory neurons was altered following systemic administration of paclitaxel, we injected male Sprague Dawley rats with 1 mg/kg paclitaxel every other day for a total of four doses and exa...

  6. Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction

    OpenAIRE

    Flatters, Sarah J.L.; Bennett, Gary J.

    2006-01-01

    Paclitaxel chemotherapy frequently induces neuropathic pain during and often persisting after therapy. The mechanisms responsible for this pain are unknown. Using a rat model of paclitaxel-induced painful peripheral neuropathy, we have performed studies to search for peripheral nerve pathology. Paclitaxel-induced mechano-allodynia and mechano-hyperalgesia were evident after a short delay, peaked at day 27 and finally resolved on day 155. Paclitaxel- and vehicle-treated rats were perfused on d...

  7. A comparative analysis of quality management standards for contract research organisations in clinical trials.

    Science.gov (United States)

    Murray, Elizabeth; McAdam, Rodney

    2007-01-01

    This article compares and contrasts the main quality standards in the highly regulated pharmaceutical industry with specific focus on Good Clinical Practice (GCP), the standard for designing, conducting, recording and reporting clinical trials involving human participants. Comparison is made to ISO quality standards, which can be applied to all industries and types of organisation. The study is then narrowed to that of contract research organisations (CROs) involved in the conduct of clinical trials. The paper concludes that the ISO 9000 series of quality standards can act as a company-wide framework for quality management within such organisations by helping to direct quality efforts on a long-term basis without any loss of compliance. This study is valuable because comparative analysis in this domain is uncommon.

  8. Prospective controlled trial comparing colostomy irrigation with "spontaneous-action" method.

    OpenAIRE

    Williams, N S; Johnston, D

    1980-01-01

    Thirty randomly selected patients with permanent colostomies entered a prospective controlled trial comparing colostomy irrigation with spontaneous action. Each patient was interviewed and examined before irrigation was begun and again after the technique had been used for three months. Each then reverted to spontaneous action for a further three months and was then reassessed. Eight patients abandoned irrigation and 22 (73%) adhered to the protocol. Irrigation caused no mishaps or complicati...

  9. Randomized Trial of a Smartphone Mobile Application Compared to Text Messaging to Support Smoking Cessation

    OpenAIRE

    Buller, David B.; Borland, Ron; Bettinghaus, Erwin P.; Shane, James H.; Zimmerman, Donald E.

    2014-01-01

    Background: Text messaging has successfully supported smoking cessation. This study compares a mobile application with text messaging to support smoking cessation. Materials and Methods: Young adult smokers 18–30 years old (n=102) participated in a randomized pretest–posttest trial. Smokers received a smartphone application (REQ-Mobile) with short messages and interactive tools or a text messaging system (onQ), managed by an expert system. Self-reported usability of REQ-Mobile and qu...

  10. CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials

    OpenAIRE

    Patrick, Kevin; Wolszon, Laura; Basen-Engquist, Karen M; Demark-Wahnefried, Wendy; Prokhorov, Alex V; Barrera, Stephanie; Baru, Chaitan; Farcas, Emilia; Krueger, Ingolf; Palmer, Doug; Raab, Fred; Rios, Phil; Ziftci, Celal; Peterson, Susan

    2010-01-01

    ABSTRACT Improved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of kn...

  11. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy

    Science.gov (United States)

    Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

    2015-01-01

    Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P neuropathy (P peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449

  12. Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer.

    Science.gov (United States)

    Chow, L W-C; Xu, B; Gupta, S; Freyman, A; Zhao, Y; Abbas, R; Vo Van, M-L; Bondarenko, I

    2013-05-28

    ). Pharmacokinetic analyses indicated no interaction between neratinib and paclitaxel. The combination of neratinib and paclitaxel was associated with higher toxicity than that of neratinib as a single agent, but was manageable with antidiarrhoeal agents and dose reductions in general. The combination therapy also demonstrated a high rate of response in patients with HER2-positive breast cancer. A phase III trial is ongoing to assess the benefit and risk of this combination in the first-line setting.

  13. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial.

    Science.gov (United States)

    von Minckwitz, Gunter; Colleoni, Marco; Kolberg, Hans-Christian; Morales, Serafin; Santi, Patricia; Tomasevic, Zorica; Zhang, Nan; Hanes, Vladimir

    2018-06-04

    ABP 980 (Amgen Inc, Thousand Oaks, CA, USA) is a biosimilar of trastuzumab, with analytical, functional, and pharmacokinetic similarities. We compared the clinical safety and efficacy of ABP 980 with that of trastuzumab in women with HER2-positive early breast cancer. We did a randomised, multicentre, double-blind, active-controlled equivalence trial at 97 study centres in 20 countries, mainly in Europe and South America. Eligible women were aged 18 years or older, had histologically confirmed HER2-positive invasive early breast cancer, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and were planning to have surgical resection of the breast tumour with sentinel or axillary lymph node dissection and neoadjuvant chemotherapy. After four cycles of run-in anthracycline-based chemotherapy, patients were assigned 1:1 to receive ABP 980 or trastuzumab with a permuted block design (blocks of four) computer-generated randomisation schedule. Patients received neoadjuvant therapy with a loading dose (8 mg/kg) of ABP 980 or trastuzumab plus paclitaxel 175 mg/m 2 in a 90 min intravenous infusion, followed by three cycles of 6 mg/kg intravenous ABP 980 or trastuzumab plus paclitaxel 175 mg/m 2 every 3 weeks in 30 min intravenous infusions (or 80 mg/m 2 paclitaxel once per week for 12 cycles if that was the local standard of care). Randomisation was stratified by T stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographical region. Surgery was completed 3-7 weeks after the last dose of neoadjuvant treatment, after which adjuvant treatment with ABP 980 or trastuzumab was given every 3 weeks for up to 1 year after the first dose in the study. Patients had been randomly assigned at baseline to continue APB 980, continue trastuzumab, or switch from trastuzumab to APB 980 as their adjuvant treatment. The co-primary efficacy endpoints were risk difference and risk ratio (RR) of pathological complete response in breast

  14. Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Zhen Hua Wu

    Full Text Available The major challenges we are facing in cancer therapy with paclitaxel (PTX are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ, an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP, an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy.

  15. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial.

    Science.gov (United States)

    Firoozabadi, Mohammad Dehghani; Navabzadeh, Maryam; Roudsari, Mohammad Khodashenas; Zahmatkash, Mohsen

    2014-12-01

    Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients) and conventional treatment group (30 patients). An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months). Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6) and 32.6 (±12.7) years, respectively (P = 0.45). After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80), frequency of migraine attacks (P = 0.63) and duration of attacks per hours (P = 0.48) were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

  16. Delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen: a case report.

    Science.gov (United States)

    Sokolova, Alexandra; Chan, Onyee; Ullah, Waqas; Hamdani, Auon Abbas; Anwer, Faiz

    2017-04-11

    High-dose chemotherapy with autologous stem cell rescue is commonly used for the treatment of relapsed germ cell tumors. We report the first case of delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen. We report a case of a 21-year-old African-American man diagnosed with relapsed non-seminomatous germ cell tumor who received high-dose chemotherapy with carboplatin and etoposide following TIGER trial arm B off-protocol. His course was complicated by muscle pain and rhabdomyolysis after cycle 4 on day +12 after infusion of autologous stem cells. To the best of our knowledge, this complication has not been reported with this regimen. A differential diagnosis of sepsis and neutropenic fever along with side effects of high-dose chemotherapy were considered, but based on the timing of events, it was concluded that the etiology of rhabdomyolysis is high-dose chemotherapy. Rhabdomyolysis was successfully treated with hydration and did not recur during subsequent cycle 5. Delayed rhabdomyolysis after high-dose chemotherapy with paclitaxel, ifosfamide, carboplatin, and etoposide regimen has not been previously reported and needs to be considered for preventive strategy and prompt diagnosis and treatment to avoid renal complications. Physicians should have a low threshold to check creatine kinase enzymes in patients with unexplained muscle pain or renal insufficiency after high-dose chemotherapy.

  17. Alcohol, indomethacin, and salbutamol. A comparative trial of their use in preterm labor.

    Science.gov (United States)

    Spearing, G

    1979-02-01

    In a comparative trial, ethanol effectively arrested preterm labor for 48 hours for more in 32% of cases, a beta-adrenergic agent (salbutamol) in 60% of cases (not statistically significant), and a combination of ethanol and indomethacin in 70% of cases (statistically significant, P less than 0.5). Labor was delayed for 14 days or more in 36, 60, and 50%, respectively (not statistically significant). The numbers studied were small, and tests of statistical significance were of doubtful value. Salbutamol was more acceptable to patients and the staff than ethanol. The trial was suspended and eventually abandoned due to reports of prostaglandin synthetase inhibitors causing premature closure of the ductus arteriosus. In this series no problems were encountered with the use of indomethacin.

  18. Comparing Amazon Mechanical Turk with unpaid internet resources in online clinical trials

    Directory of Open Access Journals (Sweden)

    Eduardo Bunge

    2018-06-01

    Full Text Available Internet interventions face significant challenges in recruitment and attrition rates are typically high and problematic. Finding innovative yet scientifically valid avenues for attaining and retaining participants is therefore of considerable importance. The main goal of this study was to compare recruitment process and participants characteristics between two similar randomized control trials of mood management interventions. One of the trials (Bunge et al., 2016 was conducted with participants recruited from Amazon's Mechanical Turk (AMT, and the other trial recruited via Unpaid Internet Resources (UIR. Methods: The AMT sample (Bunge et al., 2016 consisted of 765 adults, and the UIR sample (recruited specifically for this study consisted of 329 adult US residents. Participants' levels of depression, anxiety, confidence, motivation, and perceived usefulness of the intervention were assessed. The AMT sample was financially compensated whereas the UIR was not. Results: AMT yielded higher recruitment rates per month (p < .05. At baseline, the AMT sample reported significantly lower depression and anxiety scores (p < .001 and p < .005, respectively and significantly higher mood, motivation, and confidence (all p < .001 compared to the UIR sample. AMT participants spent significantly less time on the site (p < .05 and were more likely to complete follow-ups than the UIR sample (p < .05. Both samples reported a significant increase in their level of confidence and motivation from pre- to post-intervention. AMT participants showed a significant increase in perceived usefulness of the intervention (p < .0001, whereas the UIR sample did not (p = .1642. Conclusions: By using AMT, researchers can recruit very rapidly and obtain higher retention rates; however, these participants may not be representative of the general online population interested in clinical interventions. Considering that AMT and UIR participants

  19. Bioavailability Enhancement of Paclitaxel via a Novel Oral Drug Delivery System: Paclitaxel-Loaded Glycyrrhizic Acid Micelles

    Directory of Open Access Journals (Sweden)

    Fu-Heng Yang

    2015-03-01

    Full Text Available Paclitaxel (PTX, taxol, a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05. The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.

  20. Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory

    Directory of Open Access Journals (Sweden)

    Zhao Li

    2018-01-01

    Full Text Available The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1β in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function.

  1. Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kuang-Kai; Wang, Chi-Ching; Chao, Jui-I [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30013, Taiwan (China); Zheng, Wen-Wei; Lo, Yu-Shiu; Chen, Chinpiao [Department of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan (China); Chiu, Yu-Chung; Cheng, Chia-Liang, E-mail: clcheng@mail.ndhu.edu.tw, E-mail: chinpiao@mail.ndhu.edu.tw, E-mail: jichao@faculty.nctu.edu.tw [Department of Physics, National Dong Hwa University, Hualien 97401, Taiwan (China)

    2010-08-06

    A nanoparticle-conjugated cancer drug provides a novel strategy for cancer therapy. In this study, we manipulated nanodiamond (ND), a carbon nanomaterial, to covalently link paclitaxel for cancer drug delivery and therapy. Paclitaxel was bound to the surface of 3-5 nm sized ND through a succession of chemical modifications. The ND-paclitaxel conjugation was measured by atomic force microscope and nuclear magnetic resonance spectroscopy, and confirmed with infrared spectroscopy by the detection of deuterated paclitaxel. Treatment with 0.1-50 {mu}g ml{sup -1} ND-paclitaxel for 48 h significantly reduced the cell viability in the A549 human lung carcinoma cells. ND-paclitaxel induced both mitotic arrest and apoptosis in A549 cells. However, ND alone or denatured ND-paclitaxel (after treatment with strong alkaline solution, 1 M NaOH) did not induce the damage effects on A549 cells. ND-paclitaxel was taken into lung cancer cells in a concentration-dependent manner using flow cytometer analysis. The ND-paclitaxel particles were located in the microtubules and cytoplasm of A549 cells observed by confocal microscopy. Furthermore, ND-paclitaxel markedly blocked the tumor growth and formation of lung cancer cells in xenograft SCID mice. Together, we provide a functional covalent conjugation of ND-paclitaxel, which can be delivered into lung carcinoma cells and preserves the anticancer activities on the induction of mitotic blockage, apoptosis and anti-tumorigenesis.

  2. A randomized trial comparing primary angioplasty versus stent placement for symptomatic intracranial stenosis

    Science.gov (United States)

    Qureshi, Adnan I; Chaudhry, Saqib A; Siddiq, Farhan; Majidi, Shahram; Rodriguez, Gustavo J; Suri, M Fareed K

    2013-01-01

    Background: Both primary angioplasty alone and angioplasty with a self-expanding stent have been compared in non-randomized concurrent clinical studies that suggest equivalent results. However, there is no randomized trial that has compared the two procedures in patients with symptomatic high grade intracranial stenosis. Objective: The primary aim of the randomized trial was to compare the clinical and angiographic efficacy of primary angioplasty and angioplasty followed by stent placement in preventing restenosis, stroke, requirement for second treatment, and death in patients with symptomatic intracranial stenosis. Methods: The study prospectively evaluated efficacy and safety of the two existing neurointerventional techniques for treatment of moderate intracranial stenosis (stenosis ≥ 50%) with documented failure of medical treatment or severe stenosis (≥70%) with or without failure of medical treatment. Results: A total of 18 patients were recruited in the study (mean age [±SD] was 64.7 ± 15.1 years); out of these, 12 were men. Of these 18, 10 were treated with primary angioplasty and 8 were treated with angioplasty followed by self-expanding stent. The technical success rates of intracranial angioplasty and stent placements defined as ability to achieve <30% residual stenosis when assessed by immediate post-procedure angiography was 5 of 10 and 5 of 8 patients, respectively. The total fluoroscopic time (mean [±SD]) was lower in patients undergoing primary angioplasty 37 [±11] min versus those undergoing angioplasty followed by self-expanding stent 42 [±15] min, P = 0.4321. The stroke and death rate within 1 month was very low in both patient groups (1 of 10 versus 0 of 8 patients). One patient randomized to stent placement continued to have recurrent ischemic symptoms requiring another angioplasty in the vertebral artery on post-procedure Day 2. Conclusions: The trial suggests that a randomized trial comparing primary angioplasty to angioplasty

  3. Gestational Weight Gain: Results from the Delta Healthy Sprouts Comparative Impact Trial

    Directory of Open Access Journals (Sweden)

    Jessica L. Thomson

    2016-01-01

    Full Text Available Introduction. Delta Healthy Sprouts trial was designed to test the comparative impact of two home visiting programs on weight status, dietary intake, and health behaviors of Southern African American women and their infants. Results pertaining to the primary outcome, gestational weight gain, are reported. Methods. Participants (n=82, enrolled early in their second trimester of pregnancy, were randomly assigned to one of two treatment arms. Gestational weight gain, measured at six monthly home visits, was calculated by subtracting measured weight at each visit from self-reported prepregnancy weight. Weight gain was classified as under, within, or exceeding the Institute of Medicine recommendations based on prepregnancy body mass index. Chi-square tests and generalized linear mixed models were used to test for significant differences in percentages of participants within recommended weight gain ranges. Results. Differences in percentages of participants within the gestational weight gain guidelines were not significant between treatment arms across all visits. Conclusions. Enhancing the gestational nutrition and physical activity components of an existing home visiting program is feasible in a high risk population of primarily low income African American women. The impact of these enhancements on appropriate gestational weight gain is questionable given the more basic living needs of such women. This trial is registered with ClinicalTrials.gov NCT01746394, registered 4 December 2012.

  4. Ultrasound contrast-enhanced study as an imaging biomarker for anti-cancer drug treatment: preliminary study with paclitaxel in a xenograft mouse tumor model (secondary publication)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Jong; Hwang, Sung Il; Jung, Hyun Sook; Kang, Mi Ra [Dept. of Radiology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Byun, Jong Hoe; Kong, Hoon Young [Dept. of Molecular Biology, Dankook University, Cheonan (Korea, Republic of)

    2017-10-15

    The purpose of this study was to assess tumor angiogenesis using contrast-enhanced ultrasonography (CEUS) of human prostate cancer cells (PC3) that were implanted in mice before and after paclitaxel injection. Twelve mice were injected with human PC3. The mice were grouped into two groups; one was the paclitaxel-treated group (n=6) and the other was the control group (n=6). Before administering paclitaxel into the peritoneal cavity, baseline CEUS was performed after the administration of 500 μL (1×108 microbubbles) of contrast agent. The area under the curve (AUC) up to 50 seconds after injection was derived from the time-intensity curves. After injection of paclitaxel or saline, CEUS studies were performed at the 1-week follow-up. Changes in tumor volume and the AUC in both two groups were evaluated. After CEUS, the microvessel density (MVD) was compared between the groups. In the paclitaxel-treated group, the AUC from CEUS showed a significant decrease 1-week after paclitaxel administration (P=0.030), even though the tumor volume showed no significant changes (P=0.116). In the control group, there was no significant decrease of the AUC (P=0.173). Pathologically, there was a significant difference in MVD between both groups (P=0.002). The AUC from the time intensity curve derived from CEUS showed an early change in response to the anti-cancer drug treatment that preceded the change in tumor size. The findings of CEUS could serve as an imaging biomarker for assessing tumor responses to anti-cancer drug treatment.

  5. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial

    Directory of Open Access Journals (Sweden)

    Mohammad Dehghani Firoozabadi

    2014-01-01

    Full Text Available Background: Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. Materials and Methods: This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients and conventional treatment group (30 patients. An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months. Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Results: Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6 and 32.6 (±12.7 years, respectively (P = 0.45. After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80, frequency of migraine attacks (P = 0.63 and duration of attacks per hours (P = 0.48 were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P < 0.001. Conclusion: There was no significant difference between cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

  6. Gastrointestinal permeability in ovarian cancer and breast cancer patients treated with paclitaxel and platinum

    International Nuclear Information System (INIS)

    Melichar, Bohuslav; Hyšpler, Radomír; Dragounová, Emanuela; Dvořák, Josef; Kalábová, Hana; Tichá, Alena

    2007-01-01

    Combination of platinum derivatives with paclitaxel is currently the standard front line regimen for patients with epithelial ovarian carcinoma, and represents also an active regimen in patients with metastatic breast or unknown primary carcinomas. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal mucositis induced by chemotherapy, but little is known about intestinal permeability in patients treated with paclitaxel or platinum. Intestinal permeability was assessed in 36 breast and ovarian cancer patients treated with paclitaxel/platinum combination by measuring, using capillary gas chromatography, urinary sucrose, lactulose, xylose and mannitol after oral challenge. The significance of differences during the therapy compared to pre-treatment values was studied by Wilcoxon paired test. The differences between groups of patient were studied by Mann-Whitney U test. Fisher exact test was used to compare the frequency in different subgroups. After administration of the first dose, a significant (p < 0.05) decrease in xylose absorption and increased lactulose/mannitol, sucrose/mannitol, lactulose/xylose and sucrose/xylose ratios were observed, but these parameters returned subsequently to pre-treatment levels. Patients who experienced serious (grade 3 or 4) toxicity had at baseline significantly lower percentages of xylose, mannitol and sucrose, and higher lactulose/mannitol ratio. Nine of 13 (69%) patients with baseline lactulose/mannitol ratio 0.070 or above experienced serious toxicity compared to 4 out of 23 patients (17%) with the ratio below 0.070 (p = 0.002). Post-treatment lactulose, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were significantly increased in patients with serious toxicity. A transient significant increase in lactulose/monosaccharide and sucrose/monosaccharide ratios was observed in ovarian and breast cancer patients treated with paclitaxel

  7. Long-term Outcomes of Paclitaxel-Eluting Versus Sirolimus-Eluting Stent for Percutaneous Coronary Intervention: A Meta-Analysis

    International Nuclear Information System (INIS)

    Kong, J.; Liu, P.; Fan, X.; Wen, J.; Zhang, J.; Zhen, Y.; Li, J.; Cui, Y.; Zheng, X.; Ye, Z.

    2017-01-01

    The relative long-term efficacy and safety of sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) in multiple comparative studies remains controversial. This report evaluates 29 randomized trials with 18,379 patients in whom long-term (more than 1 year) outcomes were evaluated. The primary outcomes were target lesion revascularization (TLR) and the secondary end points were death, cardiac death, myocardial infarction (MI), major adverse cardiac events (MACEs), target vessel revascularization (TVR)and stent thrombosis (ST). In comparison with PES, SES significantly reduced the long-term risk of TLR (RR=0.68; 95% CI=0.57 to 0.80, p<0.001), TVR (RR=0.69; 95% CI= 0.60 to 0.79, p<0.001) and MACE (RR=0.82; 95% CI= 0.77 to 0.88, p<0.001), while there were no significant difference with respect to death, cardiac death, MI and ST between the two groups. SES performance was significantly better for reducing the former three outcomes and comparable for the majority of the secondary end points when compared against PES. (author)

  8. A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis.

    Science.gov (United States)

    Browne, Erica N; Rathinam, Sivakumar R; Kanakath, Anuradha; Thundikandy, Radhika; Babu, Manohar; Lietman, Thomas M; Acharya, Nisha R

    2017-02-01

    To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief. A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan-uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts' estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial's primary outcome. A total of 11 of the 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03-45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1-1.2) and 0.7 (95% CrI 0.2-1.7) from the Bayesian analysis. A Bayesian analysis combining expert belief with the trial's result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT.

  9. Iohexol and iopamidol myelography in the dog: a clinical trial comparing adverse effects and myelographic quality

    International Nuclear Information System (INIS)

    Widmer, W.R.; Blevins, W.E.; Jakovljevic, S.; Teclaw, R.F.; Han, C.M.; Hurd, C.D.

    1992-01-01

    In a blind clinical trial, adverse effects after iohexol and iopamidol myelography were evaluated in 151 dogs. Eighty-one dogs were given iohexol (240 mgI/ml) and 70 dogs were given iopamidol (200 mgI/ml) by pre-determined assignment. Each dog was evaluated postmyelographically for seizures, hyperthermia, prolonged recovery from anesthesia and intensification of pre-existing neural signs. Myelographic quality was evaluated with a subjective scoring method. In comparing iohexol and iopamidol groups, there was not a statistically significant difference in the incidence of adverse effects or in myelographic quality. Iopamidol and iohexol appeared to be equally efficacious for routine canine myelography

  10. Randomized Controlled Trial Comparing Open Versus Laparoscopic Placement of a Peritoneal Dialysis Catheter and Outcomes: The CAPD I Trial.

    Science.gov (United States)

    van Laanen, Jorinde H H; Cornelis, Tom; Mees, Barend M; Litjens, Elisabeth J; van Loon, Magda M; Tordoir, Jan H M; Peppelenbosch, Arnoud G

    2018-01-01

    had a paramedian wound infection. In the laparoscopic group, 1 patient had a transient cardiac event, 1 patient had intraabdominal bleeding requiring reoperation, and 1 patient had fluid leakage that could be managed conservatively. The survival curve demonstrated a good long-term function of PD. This randomized controlled trial (RCT) comparing open vs laparoscopic placement of PD catheters demonstrates equal clinical success rates between the 2 techniques. Advanced laparoscopic techniques such as catheter fixation techniques and omentopexy might further improve clinical outcome. Copyright © 2018 International Society for Peritoneal Dialysis.

  11. Internet treatment for depression: a randomized controlled trial comparing clinician vs. technician assistance.

    Science.gov (United States)

    Titov, Nickolai; Andrews, Gavin; Davies, Matthew; McIntyre, Karen; Robinson, Emma; Solley, Karen

    2010-06-08

    Internet-based cognitive behavioural therapy (iCBT) for depression is effective when guided by a clinician, less so if unguided. Would guidance from a technician be as effective as guidance from a clinician? Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program, and 141 participants with major depressive disorder were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for depression comprising 6 online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 8 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Beck Depression Inventory (BDI-II) and the Patient Health QUESTIONnaire-9 Item (PHQ-9). Completion rates were high, and at post-treatment, both treatment groups reduced scores on the BDI-II (ptechnician-assisted groups respectively, and on the PHQ-9, were 1.54 and 1.60 respectively. At 4-month follow-up participants in the technician group had made further improvements and had significantly lower scores on the PHQ-9 than those in the clinician group. A total of approximately 60 minutes of clinician or technician time was required per participant during the 8-week treatment program. Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for depression. This form of treatment has potential to increase the capacity of existing mental health services. Australian New

  12. Similar early migration when comparing CR and PS in Triathlon™ TKA: A prospective randomised RSA trial.

    Science.gov (United States)

    Molt, Mats; Toksvig-Larsen, Sören

    2014-10-01

    The objective of this study was to compare the early migration of the cruciate retaining and posterior stabilising versions of the recently introduced Triathlon™ total knee system, with a view to predicting long term fixation performance. Sixty patients were prospectively randomised to receive either Triathlon™ posterior stabilised cemented knee prosthesis or Triathlon™ cruciate retaining cemented knee prosthesis. Tibial component migration was measured by radiostereometric analysis postoperatively and at three months, one year and two years. Clinical outcome was measured by the American Knee Society Score and Knee Osteoarthritis and Injury Outcome Score. There were no differences in rotation around the three coordinal axes or in the maximum total point motion (MTPM) during the two year follow-up. The posterior stabilised prosthesis had more posterior-anterior translation at three months and one year and more caudal-cranial translation at one year and two years. There were no differences in functional outcome between the groups. The tibial tray of the Triathlon™ cemented knee prosthesis showed similar early stability. Level I. Article focus: This was a prospective randomised trial aiming to compare the single radius posterior stabilised (PS) Triathlon™ total knee arthroplasty (TKA) to the cruciate retaining Triathlon™ TKA system with regard to fixation. Strengths and limitations of this study: Strength of this study was that it is a randomised prospective trial using an objective measuring tool. The sample size of 25-30 patients was reportedly sufficient for the screening of implants using RSA [1]. ClinicalTrials.gov Identifier: NCT00436982. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. The effects of Red Bull energy drink compared with caffeine on cycling time-trial performance.

    Science.gov (United States)

    Quinlivan, Alannah; Irwin, Christopher; Grant, Gary D; Anoopkumar-Dukie, Sheilandra; Skinner, Tina; Leveritt, Michael; Desbrow, Ben

    2015-10-01

    This study investigated the ergogenic effects of a commercial energy drink (Red Bull) or an equivalent dose of anhydrous caffeine in comparison with a noncaffeinated control beverage on cycling performance. Eleven trained male cyclists (31.7 ± 5.9 y 82.3 ± 6.1 kg, VO2max = 60.3 ± 7.8 mL · kg-1 · min-1) participated in a double-blind, placebo-controlled, crossover-design study involving 3 experimental conditions. Participants were randomly administered Red Bull (9.4 mL/kg body mass [BM] containing 3 mg/kg BM caffeine), anhydrous caffeine (3 mg/kg BM given in capsule form), or a placebo 90 min before commencing a time trial equivalent to 1 h cycling at 75% peak power output. Carbohydrate and fluid volumes were matched across all trials. Performance improved by 109 ± 153 s (2.8%, P = .039) after Red Bull compared with placebo and by 120 ± 172 s (3.1%, P = .043) after caffeine compared with placebo. No significant difference (P > .05) in performance time was detected between Red Bull and caffeine treatments. There was no significant difference (P > .05) in mean heart rate or rating of perceived exertion among the 3 treatments. This study demonstrated that a moderate dose of caffeine consumed as either Red Bull or in anhydrous form enhanced cycling time-trial performance. The ergogenic benefits of Red Bull energy drink are therefore most likely due to the effects of caffeine, with the other ingredients not likely to offer additional benefit.

  14. Comparing methods to combine functional loss and mortality in clinical trials for amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    van Eijk RPA

    2018-03-01

    Full Text Available Ruben PA van Eijk,1 Marinus JC Eijkemans,2 Dimitris Rizopoulos,3 Leonard H van den Berg,4,* Stavros Nikolakopoulos5,* 1Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands; 2Department of Biostatistics, University Medical Center Utrecht, Utrecht, the Netherlands; 3Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands; 4Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands; 5Department of Biostatistics, University Medical Center Utrecht, Utrecht, the Netherlands *These authors contributed equally to this work Objective: Amyotrophic lateral sclerosis (ALS clinical trials based on single end points only partially capture the full treatment effect when both function and mortality are affected, and may falsely dismiss efficacious drugs as futile. We aimed to investigate the statistical properties of several strategies for the simultaneous analysis of function and mortality in ALS clinical trials. Methods: Based on the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT database, we simulated longitudinal patterns of functional decline, defined by the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R and conditional survival time. Different treatment scenarios with varying effect sizes were simulated with follow-up ranging from 12 to 18 months. We considered the following analytical strategies: 1 Cox model; 2 linear mixed effects (LME model; 3 omnibus test based on Cox and LME models; 4 composite time-to-6-point decrease or death; 5 combined assessment of function and survival (CAFS; and 6 test based on joint modeling framework. For each analytical strategy, we calculated the empirical power and sample size. Results: Both Cox and LME models have increased false-negative rates when treatment exclusively affects either function or survival. The joint model has superior power compared to other strategies. The composite end point

  15. Combined doxorubicin and paclitaxel in advanced breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T

    1996-01-01

    -550). The main toxicities were neutropenia, parestesia, nausea/vomiting, alopecia, myalgia and cardiotoxicity. Fifteen patients (50%) had reductions of left ventricular ejection fraction of below normal levels and 6 of these patients (20%) developed congestive heart failure. CONCLUSION: The combination...... of doxorubicin and paclitaxel is highly active, but is accompanied by the dose-limiting toxic effects of neutropenia, neuropathy and cardiotoxicity....

  16. Polyelectrolyte stabilized multilayered liposomes for oral delivery of paclitaxel

    DEFF Research Database (Denmark)

    Jain, Sanyog; Kumar, Dinesh; Swarnakar, Nitin K

    2012-01-01

    Paclitaxel (PTX) loaded layersome formulations were prepared using layer-by-layer assembly of the polyelectrolytes over liposomes. Stearyl amine was utilized to provide positive charge to the liposomes, which were subsequently coated with anionic polymer polyacrylic acid (PAA) followed by coating...

  17. Comparative effectiveness of injection therapies in lateral epicondylitis: a systematic review and network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Krogh, Thøger Persson; Bartels, Else Marie; Ellingsen, Torkell; Stengaard-Pedersen, Kristian; Buchbinder, Rachelle; Fredberg, Ulrich; Bliddal, Henning; Christensen, Robin

    2013-06-01

    Injection therapy with glucocorticoids has been used since the 1950s as a treatment strategy for lateral epicondylitis (tennis elbow). Lately, several novel injection therapies have become available. To assess the comparative effectiveness and safety of injection therapies in patients with lateral epicondylitis. Systematic review and meta-analysis. Randomized controlled trials comparing different injection therapies for lateral epicondylitis were included provided they contained data for change in pain intensity (primary outcome). Trials were assessed using the Cochrane risk of bias tool. Network (random effects) meta-analysis was applied to combine direct and indirect evidence within and across trial data using the final end point reported in the trials, and results for the arm-based network analyses are reported as standardized mean differences (SMDs). Seventeen trials (1381 participants; 3 [18%] at low risk of bias) assessing injection with 8 different treatments-glucocorticoid (10 trials), botulinum toxin (4 trials), autologous blood (3 trials), platelet-rich plasma (2 trials), and polidocanol, glycosaminoglycan, prolotherapy, and hyaluronic acid (1 trial each)-were included. Pooled results (SMD [95% confidence interval]) showed that beyond 8 weeks, glucocorticoid injection was no more effective than placebo (-0.04 [-0.45 to 0.35]), but only 1 trial (which did not include a placebo arm) was at low risk of bias. Although botulinum toxin showed marginal benefit (-0.50 [-0.91 to -0.08]), it caused temporary paresis of finger extension, and all trials were at high risk of bias. Both autologous blood (-1.43 [-2.15 to -0.71]) and platelet-rich plasma (-1.13 [-1.77 to -0.49]) were also statistically superior to placebo, but only 1 trial was at low risk of bias. Prolotherapy (-2.71 [-4.60 to -0.82]) and hyaluronic acid (-5.58 [-6.35 to -4.82]) were both more efficacious than placebo, whereas polidocanol (0.39 [-0.42 to 1.20]) and glycosaminoglycan (-0.32 [-1.02 to 0

  18. Behavioral Effects of Neurofeedback Compared to Stimulants and Physical Activity in Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Geladé, Katleen; Janssen, Tieme W. P.; Bink, Marleen; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

    2016-01-01

    The efficacy of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD), and whether neurofeedback is a viable alternative for stimulant medication, is still an intensely debated subject. The current randomized controlled trial compared neurofeedback to (1) optimally

  19. Behavioral Effects of Neurofeedback Compared to Stimulants and Physical Activity in Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Gelade, K.; Janssen, T.W.P.; Bink, M.; van Mourik, R.; Maras, A.; Oosterlaan, J.

    2016-01-01

    Objective: The efficacy of neurofeedback as treatment for attention-deficit/hyperactivity disorder (ADHD), and whether neurofeedback is a viable alternative for stimulant medication, are still intensely debated subjects. The current randomised controlled trial compared neurofeedback to (1) optimally

  20. Low doses of Paclitaxel repress breast cancer invasion through DJ-1/KLF17 signalling pathway.

    Science.gov (United States)

    Ismail, Ismail Ahmed; El-Sokkary, Gamal H; Saber, Saber H

    2018-04-27

    Paclitaxel (taxol) is an important agent against many tumours, including breast cancer. Ample data documents that paclitaxel inhibits breast cancer metastasis while others prove that paclitaxel enhances breast cancer metastasis. The mechanisms by which paclitaxel exerts its action are not well established. This study focuses on the effect of paclitaxel, particularly the low doses on breast cancer metastasis and the mechanisms that regulate it. Current results show that, paclitaxel exerts significant cytotoxicity even at low doses in both MCF-7 and MDA-MB-231 cells. Interestingly, paclitaxel significantly inhibits cell invasion and migration, decreases Snail and increases E-cadherin mRNA expression levels at the indicated low doses. Furthermore, paclitaxel-inhibiting breast cancer metastasis is associated with down-regulation of DJ-1 and ID-1 mRNA expression level with a concurrent increase in KLF17 expression. Under the same experimental conditions, paclitaxel induces KLF17 and concurrently represses ID-1 protein levels. Our results show for the first time that paclitaxel inhibits breast cancer metastasis through regulating DJ-1/KLF17/ID-1 signalling pathway; repressed DJ-1 and ID-1 and enhanced KLF17 expression. © 2018 John Wiley & Sons Australia, Ltd.

  1. The IDvIP Trial: A two-centre randomised double-blind controlled trial comparing intramuscular diamorphine and intramuscular pethidine for labour analgesia

    Directory of Open Access Journals (Sweden)

    Thomas Peter

    2011-07-01

    Full Text Available Abstract Background Intramuscular pethidine is routinely used throughout the UK for labour analgesia. Studies have suggested that pethidine provides little pain relief in labour and has a number of side effects affecting mother and neonate. It can cause nausea, vomiting and dysphoria in mothers and can cause reduced fetal heart rate variability and accelerations. Neonatal effects include respiratory depression and impaired feeding. There are few large studies comparing the relative side effects and efficacy of different opioids in labour. A small trial comparing intramuscular pethidine with diamorphine, showed diamorphine to have some benefits over pethidine when used for labour analgesia but the study did not investigate the adverse effects of either opioid. Methods The Intramuscular Diamorphine versus Intramuscular Pethidine (IDvIP trial is a randomised double-blind two centre controlled trial comparing intramuscular diamorphine and pethidine regarding their analgesic efficacy in labour and their side effects in mother, fetus and neonate. Information about the trial will be provided to women in the antenatal period or in early labour. Consent and recruitment to the trial will be obtained when the mother requests opioid analgesia. The sample size requirement is 406 women with data on primary outcomes. The maternal primary outcomes are pain relief during the first 3 hours after trial analgesia and specifically pain relief after 60 minutes. The neonatal primary outcomes are need for resuscitation and Apgar Score Discussion If the trial demonstrates that diamorphine provides better analgesia with fewer side effects in mother and neonate this could lead to a change in national practice and result in diamorphine becoming the preferred intramuscular opioid for analgesia in labour. Trial Registration ISRCTN14898678 Eudra No: 2006-003250-18, REC Reference No: 06/Q1702/95, MHRA Authorisation No: 1443/0001/001-0001, NIHR UKCRN reference 6895, RfPB grant

  2. Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial

    Science.gov (United States)

    Schmid, Christopher H; Fielding, Roger A; Harvey, William F; Reid, Kieran F; Price, Lori Lyn; Driban, Jeffrey B; Kalish, Robert; Rones, Ramel; McAlindon, Timothy

    2018-01-01

    Abstract Objectives To determine the effectiveness of tai chi interventions compared with aerobic exercise, a current core standard treatment in patients with fibromyalgia, and to test whether the effectiveness of tai chi depends on its dosage or duration. Design Prospective, randomized, 52 week, single blind comparative effectiveness trial. Setting Urban tertiary care academic hospital in the United States between March 2012 and September 2016. Participants 226 adults with fibromyalgia (as defined by the American College of Rheumatology 1990 and 2010 criteria) were included in the intention to treat analyses: 151 were assigned to one of four tai chi groups and 75 to an aerobic exercise group. Interventions Participants were randomly assigned to either supervised aerobic exercise (24 weeks, twice weekly) or one of four classic Yang style supervised tai chi interventions (12 or 24 weeks, once or twice weekly). Participants were followed for 52 weeks. Adherence was rigorously encouraged in person and by telephone. Main outcome measures The primary outcome was change in the revised fibromyalgia impact questionnaire (FIQR) scores at 24 weeks compared with baseline. Secondary outcomes included changes of scores in patient’s global assessment, anxiety, depression, self efficacy, coping strategies, physical functional performance, functional limitation, sleep, and health related quality of life. Results FIQR scores improved in all five treatment groups, but the combined tai chi groups improved statistically significantly more than the aerobic exercise group in FIQR scores at 24 weeks (difference between groups=5.5 points, 95% confidence interval 0.6 to 10.4, P=0.03) and several secondary outcomes (patient’s global assessment=0.9 points, 0.3 to 1.4, P=0.005; anxiety=1.2 points, 0.3 to 2.1, P=0.006; self efficacy=1.0 points, 0.5 to 1.6, P=0.0004; and coping strategies, 2.6 points, 0.8 to 4.3, P=0.005). Tai chi treatment compared with aerobic exercise administered with

  3. FLOW (finding lasting options for women): multicentre randomized controlled trial comparing tampons with menstrual cups.

    Science.gov (United States)

    Howard, Courtney; Rose, Caren Lee; Trouton, Konia; Stamm, Holly; Marentette, Danielle; Kirkpatrick, Nicole; Karalic, Sanja; Fernandez, Renee; Paget, Julie

    2011-06-01

    To determine whether menstrual cups are a viable alternative to tampons. Randomized controlled trial. Prince George, Victoria, and Vancouver, BC. A total of 110 women aged 19 to 40 years who had previously used tampons as their main method of menstrual management. Participants were randomized into 2 groups, a tampon group and a menstrual cup group. Using online diaries, participants tracked 1 menstrual cycle using their regular method and 3 menstrual cycles using the method of their allocated group. Overall satisfaction; secondary outcomes included discomfort, urovaginal infection, cost, and waste. Forty-seven women in each group completed the final survey, 5 of whom were subsequently excluded from analysis (3 from the tampon group and 2 from the menstrual cup group). Overall satisfaction on a 7-point Likert scale was higher for the menstrual cup group than for the tampon group (mean [standard deviation] score 5.4 [1.5] vs 5.0 [1.0], respectively; P=.04). Approximately 91% of women in the menstrual cup group said they would continue to use the cup and recommend it to others. Women used a median of 13 menstrual products per cycle, or 169 products per year, which corresponds to approximately 771,248,400 products used annually in Canada. Estimated cost for tampon use was $37.44 a year (similar to the retail cost of 1 menstrual cup). Subjective vaginal discomfort was initially higher in the menstrual cup group, but the discomfort decreased with continued use. There was no significant difference in physician-diagnosed urovaginal symptoms between the 2 groups. Both of the menstrual management methods evaluated were well tolerated by subjects. Menstrual cups are a satisfactory alternative to tampons and have the potential to be a sustainable solution to menstrual management, with moderate cost savings and much-reduced environmental effects compared with tampons. Trial registration number C06-0478 (ClinicalTrials.gov).

  4. Hydrophobically modified inulin as an amphiphilic carbohydrate polymer for micellar delivery of paclitaxel for intravenous route.

    Science.gov (United States)

    Muley, Pratik; Kumar, Sunny; El Kourati, Fadoua; Kesharwani, Siddharth S; Tummala, Hemachand

    2016-03-16

    Micellization offers several advantages for the delivery of water insoluble drugs including a nanoparticulate 'core-shell' delivery system for drug targeting. Recently, hydrophobically modified polysaccharides (HMPs) are gaining recognition as micelle forming polymers to encapsulate hydrophobic drugs. In this manuscript, for the first time, we have evaluated the self-assembling properties of a lauryl carbamate derivative of the poly-fructose natural polymer inulin (Inutec SP1(®) (INT)) to form paclitaxel (PTX) loaded micelles. INT self-assembled into well-defined micellar structures in aqueous environment with a low critical micellar concentration of 27.8 μg/ml. INT micelles exhibited excellent hemocompatibility and low toxicity to cultured cells. PTX loaded INT micelles exhibited a mean size of 256.37 ± 10.45 nm with excellent drug encapsulation efficiency (95.66 ± 2.25%) and loading (8.69 ± 0.22%). PTX loaded micelles also displayed sustained release of PTX and enhanced anti-cancer efficacy in-vitro in mouse melanoma cells (B16F10) compared to Taxol formulation with Cremophor EL as solvent. In addition, PTX loaded INT micelles exhibited comparable in-vivo antitumor activity in B16F10 allograft mouse model at half the dose of Taxol. In conclusion, INT offers safe, inexpensive and natural alternative to widely used PEG-modified polymers for the formulation of micellar delivery systems for paclitaxel. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Study on the effect of paclitaxel nanostructure lipid carrier cooperated with radiation on the KB Cells

    International Nuclear Information System (INIS)

    Liu Min; Li Zhihui; Xu Yujie

    2011-01-01

    Objective: To investigate the cytotoxicity effect of paclitaxel nanostructure lipid carrier (TAX-NLC) cooperated with radiation treatment on the KB cells. Methods: The cytotoxicity effect of TAX-NLC compared with free paclitaxel (TAX) on the KB cells was measured by MTT assay, and the cell cycle distribution was analyzed by flow cytometry. Results: The cytotoxicity effect of TAX-NLC was stronger than that of the free TAX. And the cooperative effect between the TAX-NLC and ionized radiation were observed, the cooperative effect of TAX-NLC was stronger than that of the free TAX. Flow cytometric analysis indicated that the rearrangement of cell cycle in KB cells were induced by TAX-NLC. The more G2/M phase cells were observed in KB cells treated by TAX-NLC compared with free TAX. The effect of TAX-NLC in the rearrangement of cell cycle was stronger than that of the free TAX. Conclusion: The cytotoxicity effect of TAX-NLC is stronger than that of the free TAX. And the cooperative effect of TAX-NLC is stronger than that of the free TAX. (authors)

  6. Dextrose saline compared with normal saline rehydration of hyperemesis gravidarum: a randomized controlled trial.

    Science.gov (United States)

    Tan, Peng Chiong; Norazilah, Mat Jin; Omar, Siti Zawiah

    2013-02-01

    To compare 5% dextrose-0.9% saline against 0.9% saline solution in the intravenous rehydration of hyperemesis gravidarum. Women at their first hospitalization for hyperemesis gravidarum were enrolled on admission to the ward and randomly assigned to receive either 5% dextrose-0.9% saline or 0.9% saline by intravenous infusion at a rate 125 mL/h over 24 hours in a double-blind trial. All participants also received thiamine and an antiemetic intravenously. Oral intake was allowed as tolerated. Primary outcomes were resolution of ketonuria and well-being (by 10-point visual numerical rating scale) at 24 hours. Nausea visual numerical rating scale scores were obtained every 8 hours for 24 hours. Persistent ketonuria rates after the 24-hour study period were 10 of 101 (9.9%) compared with 11 of 101 (10.9%) (P>.99; relative risk 0.9, 95% confidence interval 0.4-2.2) and median (interquartile range) well-being scores at 24 hours were 9 (8-10) compared with 9 (8-9.5) (P=.73) in the 5% dextrose-0.9% saline and 0.9% saline arms, respectively. Repeated measures analysis of variance of the nausea visual numerical rating scale score as assessed every 8 hours during the 24-hour study period showed a significant difference in favor of the 5% dextrose-0.9% saline arm (P=.046) with the superiority apparent at 8 and 16 hours, but the advantage had dissipated by 24 hours. Secondary outcomes of vomiting, resolution of hyponatremia, hypochloremia and hypokalemia, length of hospitalization, duration of intravenous antiemetic, and rehydration were not different. Intravenous rehydration with 5% dextrose-0.9% saline or 0.9% saline solution in women hospitalized for hyperemesis gravidarum produced similar outcomes. ISRCTN Register, www.controlled-trials.com/isrctn, ISRCTN65014409. I.

  7. Role of cytochrome P450 2C8*3 (CYP2C8*3) in paclitaxel metabolism and paclitaxel-induced neurotoxicity

    DEFF Research Database (Denmark)

    Lee, Mi-Young; Apellániz-Ruiz, María; Johansson, Inger

    2015-01-01

    AIM: The CYP2C8*3 allele has been suggested as a risk factor for paclitaxel-induced neuropathy but the data hitherto published are conflicting. MATERIALS & METHODS: In total 435 patients were investigated with respect to maximum neuropathy grade and accumulated paclitaxel dose. The enzymatic prop...

  8. A Randomized Trial Comparing Two Tongue-Pressure Resistance Training Protocols for Post-Stroke Dysphagia.

    Science.gov (United States)

    Steele, Catriona M; Bayley, Mark T; Peladeau-Pigeon, Melanie; Nagy, Ahmed; Namasivayam, Ashwini M; Stokely, Shauna L; Wolkin, Talia

    2016-06-01

    The objective of this study was to compare the outcomes of two tongue resistance training protocols. One protocol ("tongue-pressure profile training") emphasized the pressure-timing patterns that are typically seen in healthy swallows by focusing on gradual pressure release and saliva swallowing tasks. The second protocol ("tongue-pressure strength and accuracy training") emphasized strength and accuracy in tongue-palate pressure generation and did not include swallowing tasks. A prospective, randomized, parallel allocation trial was conducted. Of 26 participants who were screened for eligibility, 14 received up to 24 sessions of treatment. Outcome measures of posterior tongue strength, oral bolus control, penetration-aspiration and vallecular residue were made based on videofluoroscopy analysis by blinded raters. Complete data were available for 11 participants. Significant improvements were seen in tongue strength and post-swallow vallecular residue with thin liquids, regardless of treatment condition. Stage transition duration (a measure of the duration of the bolus presence in the pharynx prior to swallow initiation, which had been chosen to capture impairments in oral bolus control) showed no significant differences. Similarly, significant improvements were not seen in median scores on the penetration-aspiration scale. This trial suggests that tongue strength can be improved with resistance training for individuals with tongue weakness following stroke. We conclude that improved penetration-aspiration does not necessarily accompany improvements in tongue strength; however, tongue-pressure resistance training does appear to be effective for reducing thin liquid vallecular residue.

  9. A Randomized Trial Comparing Acupuncture, Simulated Acupuncture, and Usual Care for Chronic Low Back Pain

    Science.gov (United States)

    Cherkin, Daniel C.; Sherman, Karen J.; Avins, Andrew L.; Erro, Janet H.; Ichikawa, Laura; Barlow, William E.; Delaney, Kristin; Hawkes, Rene; Hamilton, Luisa; Pressman, Alice; Khalsa, Partap S.; Deyo, Richard A.

    2009-01-01

    Background Acupuncture is a popular complementary and alternative treatment for chronic back pain. Recent European trials suggest similar short-term benefits from real and sham acupuncture needling. This trial addresses the importance of needle placement and skin penetration in eliciting acupuncture effects for patients with chronic low back pain. Methods 638 adults with chronic mechanical low back pain were randomized to: individualized acupuncture, standardized acupuncture, simulated acupuncture, or usual care. Ten treatments were provided over 7 weeks by experienced acupuncturists. The primary outcomes were back-related dysfunction (Roland Disability score, range: 0 to 23) and symptom bothersomeness (0 to 10 scale). Outcomes were assessed at baseline and after 8, 26 and 52 weeks. Results At 8 weeks, mean dysfunction scores for the individualized, standardized, and simulated acupuncture groups improved by 4.4, 4.5, and 4.4 points, respectively, compared with 2.1 points for those receiving usual care (P0.05). Conclusions Although acupuncture was found effective for chronic low back pain, tailoring needling sites to each patient and penetration of the skin appear to be unimportant in eliciting therapeutic benefits. These findings raise questions about acupuncture’s purported mechanisms of action. It remains unclear whether acupuncture, or our simulated method of acupuncture, provide physiologically important stimulation or represent placebo or non-specific effects. PMID:19433697

  10. Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Ayumu Matsuoka

    Full Text Available Bevacizumab (BEV, a humanized anti-vascular endothelial growth factor (VEGF monoclonal antibody, enhances the antitumor effectiveness of paclitaxel (PTX-based chemotherapy in many metastatic cancers. A recent study in mice showed that VEGF receptor inhibitors can interfere with the neuroprotective effects of endogenous VEGF, potentially triggering the exacerbation of PTX-induced neuropathy. In clinical trials, exacerbation of neuropathy in patients who received PTX combined with BEV (PTX+BEV has generally been explained by increased exposure to PTX owing to the extended duration of chemotherapy. We investigated whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy.Female patients with breast cancer who had received weekly PTX or PTX+BEV from September 2011 through May 2016 were studied retrospectively. PTX-induced neuropathy was evaluated at the same time points (at the 6th and 12th courses of chemotherapy in both cohorts. A multivariate Cox proportional-hazards model was used to assess the independent effect of BEV on the time to the onset of neuropathy.A total of 107 patients (median age, 55 years; range, 32-83 were studied. Sixty-one patients received PTX as adjuvant chemotherapy, 23 received PTX for metastatic disease, and 23 received PTX+BEV for metastatic disease. Peripheral sensory neuropathy was worse in patients who received PTX+BEV than in those who received PTX alone: at the 6th course, Grade 0/1/2/3 = 4/13/4/0 vs. 25/42/6/0 (P = 0.095; at the 12th course, 2/3/11/3 vs. 7/30/23/2 (P = 0.016. At the 12th course, the incidence of Grade 2 or higher neuropathy was significantly higher in patients treated with PTX+BEV than in those treated with PTX alone (74% vs. 40%; P = 0.017. In multivariate analysis, BEV was significantly associated with an increased risk of neuropathy (HR 2.32, 95% CI 1.21-4.44, P = 0.012.The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast

  11. Effect of Surface-Modified Paclitaxel Nanowires on U937 Cells In Vitro: A Novel Drug Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Mohamed H. Abumaree

    2012-01-01

    Full Text Available We have fabricated surface-modified paclitaxel nanowires (SM-PNs with a precise diameter and an average length of 50 μm. The surface of these nanowires is coated with a monolayer of octadecylsiloxane (ODS, which prevents aggregation and enhances dispersivity in aqueous media. This system constitutes a novel drug delivery vehicle based on one-dimensional (1D nanostructures with a large drug to vehicle ratio. We assayed the cytotoxicity of different diameter SM-PNs (200, 80, 35, and 18 nm with U937 cells and compared their activity to microcrystalline paclitaxel. SM-PNs reduced U937 cell proliferation in culture followed by cell death. For the same amount of paclitaxel, different diameter SM-PNs displayed different cytotoxic effect at the same incubation time period. SM-PNs with 35 nm diameters were the most efficient in completely halting cell proliferation following the first 24 hours of treatment, associated with 42% cell death. SM-PNs with 18 nm diameters were least effective. These SM-PNs can be tailored to fit a certain treatment protocol by simply choosing the appropriate diameter.

  12. Safety and Efficacy of Low-dose Nanoparticle Albumin-bound Paclitaxel for HER2-negative Metastatic Breast Cancer.

    Science.gov (United States)

    Takashima, Tsutomu; Kawajiri, Hidemi; Nishimori, Takeo; Tei, Seika; Nishimura, Shigehiko; Yamagata, Shigehito; Tokunaga, Shinya; Mizuyama, Yoko; Sunami, Takeshi; Tezuka, Kenji; Ikeda, Katsumi; Ogawa, Yoshinari; Kashiwagi, Shinichiro; Noda, Satoru; Onoda, Naoyoshi; Ishikawa, Tetsuro; Kudoh, Shinzoh; Takada, Minoru; Hirakawa, Kosei; Ohira, Masaichi

    2018-01-01

    Nab-paclitaxel (nab-PTX) is an albumin-bound paclitaxel formulation. Although nab-PTX has shown superior efficacy compared to conventional paclitaxel (PTX) in metastatic breast cancer (MBC), chemotherapy-induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In this study, we aimed to estimate the feasibility of the nab-PTX 175 mg/m 2 /3weeks regimen. Patients having metastatic or inoperable HER2-negative breast cancer received 175 mg/m 2 of nab-PTX every three weeks. The primary endpoint was safety and the secondary endpoints were response and survival. Seventeen patients were enrolled with a median age of 64 years. Ten patients had estrogen receptor positive disease and seven had triple-negative disease. CIPN was observed in seven patients (41%) however, grade 3 CIPN was only seen in one patient (6%). Objective response rate was 41% and progression-free survival was 23 weeks. Nab-PTX 175 mg/m 2 /3wks regimen has a good safety profile and less frequent CIPN. This regimen can contribute to the strategy of MBC treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Comparative randomised active drug controlled clinical trial of a herbal eye drop in computer vision syndrome.

    Science.gov (United States)

    Chatterjee, Pranab Kr; Bairagi, Debasis; Roy, Sudipta; Majumder, Nilay Kr; Paul, Ratish Ch; Bagchi, Sunil Ch

    2005-07-01

    A comparative double-blind placebo-controlled clinical trial of a herbal eye drop (itone) was conducted to find out its efficacy and safety in 120 patients with computer vision syndrome. Patients using computers for more than 3 hours continuously per day having symptoms of watering, redness, asthenia, irritation, foreign body sensation and signs of conjunctival hyperaemia, corneal filaments and mucus were studied. One hundred and twenty patients were randomly given either placebo, tears substitute (tears plus) or itone in identical vials with specific code number and were instructed to put one drop four times daily for 6 weeks. Subjective and objective assessments were done at bi-weekly intervals. In computer vision syndrome both subjective and objective improvements were noticed with itone drops. Itone drop was found significantly better than placebo (pcomputer vision syndrome.

  14. A Randomized Controlled Trial Comparing Telemedical and Standard Outpatient Monitoring of Diabetic Foot Ulcers

    DEFF Research Database (Denmark)

    Rasmussen, Benjamin S B; Froekjaer, Johnny; Bjerregaard, Mads R

    2015-01-01

    OBJECTIVE: The role of telemedical monitoring in diabetic foot ulcer care is still uncertain. Our aim was to compare telemedical and standard outpatient monitoring in the care of patients with diabetic foot ulcers in a randomized controlled trial. RESEARCH DESIGN AND METHODS: Of the 736 screened...... individuals with diabetic foot ulcers, 401 met the eligibility criteria and were randomized between October 2010 and November 2014. The per-protocol telemedical monitoring consisted of two consultations in the patient's own home and one consultation at the outpatient clinic. Standard practice consisted...... monitoring, a higher mortality throws into question the role of telemedicine in monitoring diabetic foot ulcers. Further studies are needed to investigate effects of telemedicine on mortality and other clinical outcomes and to identify patient subgroups that may have a poorer outcome through telemedical...

  15. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

    Directory of Open Access Journals (Sweden)

    Kuniaki Tsutsumi

    2016-06-01

    Full Text Available Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7 and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor-bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy.

  16. Comparability of patients with ANCA-associated vasculitis enrolled in clinical trials or in observational cohorts

    Science.gov (United States)

    Pagnoux, Christian; Carette, Simon; Khalidi, Nader A.; Walsh, Michael; Hiemstra, Thomas F.; Cuthbertson, David; Langford, Carol; Hoffman, Gary S.; Koening, Curry L.; Monach, Paul A.; Moreland, Larry; Mouthon, Luc; Seo, Phil; Specks, Ulrich; Ytterberg, Steven; Westman, Kerstin; Hoglund, Peter; Harper, Lorraine; Flossmann, Oliver; Luqmani, Raashid; Savage, Caroline; Rasmussen, Niels; de Groot, Kirstin; Tesar, Vladimir; Jayne, David; Merkel, Pater A.; Guillevin, Loic

    2015-01-01

    Objective To analyse the differences between patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) entered into randomised clinical trials (RCTs) and those followed in large observational cohorts. Methods The main characteristics and outcomes of patients with generalised and/or severe GPA or MPA with a five-factor score ≥1 enrolled in the French Vasculitis Study Group (FVSG) or the US-Canadian-based Vasculitis Clinical Research Consortium cohorts were compared to those enrolled in one of 2 FVSG clinical RCTs (WEG91, WEGENT) or 3 European Vasculitis Society clinical trials (CYCLOPS, CYCAZAREM, IMPROVE). Results 657 patients (65.3% with GPA) in RCTs were compared to 437 in cohorts (90.6% with GPA). RCT patients were older at diagnosis than the cohort patients (56.6±13.9 vs. 46.8±17.3 years), had higher Birmingham vasculitis activity score (19.5±9.1 vs. 16.9±7.4), and more frequent kidney disease (84.0% vs. 54.9%) but fewer ear, nose, and throat symptoms (56.8% vs. 72.2%). At 56 months post-diagnosis, mortality and relapse rates, adjusted for age and renal function, were higher for patients with GPA in RCTs vs. cohorts (10.7% vs. 2.5% [p=0.001] and 22.5% vs. 15.6% [p=0.03], respectively) but similar for patients with MPA (6.2% vs. 6.6% [p=0.92] and 16.6% vs. 10.1% [p=0.39], respectively). Conclusion Patients with GPA or MPA in RCTs and those in observational cohorts show important differences that should be remembered when interpreting results based on these study populations. PMID:26016754

  17. Economic evaluation of the randomized European Achalasia trial comparing pneumodilation with Laparoscopic Heller myotomy.

    Science.gov (United States)

    Moonen, A; Busch, O; Costantini, M; Finotti, E; Tack, J; Salvador, R; Boeckxstaens, G; Zaninotto, G

    2017-11-01

    A recent multicenter randomized trial in achalasia patients has shown that pneumatic dilation resulted in equivalent relief of symptoms compared to laparoscopic Heller myotomy. Additionally, the cost of each treatment should be also taken in consideration. Therefore, the aim of the present study was to perform an economic analysis of the European achalasia trial. Patients with newly diagnosed achalasia were enrolled from to 2003 to 2008 in 14 centers in five European countries and were randomly assigned to either pneumatic dilation (PD) or laparoscopic Heller (LHM). The economic analysis was performed in the three centers in three different countries where most patients were enrolled (Amsterdam [NL], Leuven, [B] and Padova [I]) and then applied to all patients included in the study. The total raw costs of the two treatments per patient include the initial costs, the costs of complications, and the costs of retreatments. Two hundred and one patients, 107 (57 males and 50 females, mean age 46 CI: 43-49 years) were randomized to LHM and 94 (59 males and 34 females, mean age 46 CI 43-50 years) to PD. The total cost of PD per patient was quite comparable in the three different centers; €3397 in Padova, €3259 in Amsterdam and €3792 in Leuven. For LHM, the total costs per patient were highest in Amsterdam: €4488 in Padova, €6720 in Amsterdam, and €5856 in Leuven. In conclusion, the strategy of treating achalasia starting with PD appears the most economic approach, independent of the health system. © 2017 John Wiley & Sons Ltd.

  18. Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

    Science.gov (United States)

    Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

    2017-01-01

    The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3 -not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D 3 . The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D 3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D 3 provide equal efficacy and safety profiles.

  19. Internet treatment for generalized anxiety disorder: a randomized controlled trial comparing clinician vs. technician assistance.

    Science.gov (United States)

    Robinson, Emma; Titov, Nickolai; Andrews, Gavin; McIntyre, Karen; Schwencke, Genevieve; Solley, Karen

    2010-06-03

    Internet-based cognitive behavioural therapy (iCBT) for generalized anxiety disorder (GAD) has been shown to be effective when guided by a clinician. The present study sought to replicate this finding, and determine whether support from a technician is as effective as guidance from a clinician. Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program and 150 participants with GAD were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for GAD comprising six online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 10 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Penn State Worry Questionnaire (PSWQ) and the Generalized Anxiety Disorder-7 Item (GAD-7). Completion rates were high, and both treatment groups reduced scores on the PSWQ (ptechnician-assisted groups, respectively, and on the GAD-7 were 1.55 and 1.73, respectively. At 3 month follow-up participants in both treatment groups had sustained the gains made at post-treatment. Participants in the clinician-assisted group had made further gains on the PSWQ. Approximately 81 minutes of clinician time and 75 minutes of technician time were required per participant during the 10 week treatment program. Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment/control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for GAD. This form of treatment has potential to increase the

  20. Novel thermo-sensitive core-shell nanoparticles for targeted paclitaxel delivery

    International Nuclear Information System (INIS)

    Li Yuanpei; Pan Shirong; Zhang Wei; Du Zhuo

    2009-01-01

    Novel thermo-sensitive nanoparticles self-assembled from poly(N,N-diethylacrylamide- co-acrylamide)-block-poly(γ-benzyl L-glutamate) were designed for targeted drug delivery in localized hyperthermia. The lower critical solution temperature (LCST) of nanoparticles was adjusted to a level between physiological body temperature (37 deg. C) and that used in local hyperthermia (about 43 deg. C). The temperature-dependent performances of the core-shell nanoparticles were systemically studied by nuclear magnetic resonance (NMR), circular dichroism (CD), fluorescence spectroscopy, dynamic light scattering (DLS), and atom force microscopy (AFM). The mean diameter of the nanoparticles increased slightly from 110 to 129 nm when paclitaxel (PTX), a poorly water-soluble anti-tumor drug, was encapsulated. A stability study in bovine serum albumin (BSA) solution indicated that the PTX loaded nanoparticles may have a long circulation time under physiological environments as the LCST was above physiological body temperature and the shell remained hydrophilic at 37 deg.C. The PTX release profiles showed thermo-sensitive controlled behavior. The proliferation inhibiting activity of PTX loaded nanoparticles was evaluated against Hela cells in vitro, compared with Taxol (a formulation of paclitaxel dissolved in Cremophor EL and ethanol). The cytotoxicity of PTX loaded nanoparticles increased obviously when hyperthermia was performed. The nanoparticles synthesized here could be an ideal candidate for thermal triggered anti-tumor PTX delivery system.

  1. The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized-controlled trial.

    Science.gov (United States)

    Walsh, Michael; Manns, Braden J; Klarenbach, Scott; Tonelli, Marcello; Hemmelgarn, Brenda; Culleton, Bruce

    2010-04-01

    Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized-controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24-0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty-one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium-phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long-term cardiovascular and bone-related outcomes requires further investigation.

  2. Protocol for the saMS trial (supportive adjustment for multiple sclerosis: a randomized controlled trial comparing cognitive behavioral therapy to supportive listening for adjustment to multiple sclerosis

    Directory of Open Access Journals (Sweden)

    McCrone Paul

    2009-08-01

    Full Text Available Abstract Background Multiple Sclerosis (MS is an incurable, chronic, potentially progressive and unpredictable disease of the central nervous system. The disease produces a range of unpleasant and debilitating symptoms, which can have a profound impact including disrupting activities of daily living, employment, income, relationships, social and leisure activities, and life goals. Adjusting to the illness is therefore particularly challenging. This trial tests the effectiveness of a Cognitive Behavioural intervention compared to Supportive Listening to assist adjustment in the early stages of MS. Methods/Design This is a two arm randomized multi-centre parallel group controlled trial. 122 consenting participants who meet eligibility criteria will be randomly allocated to receive either Cognitive Behavioral Therapy or Supportive Listening. Eight one hour sessions of therapy (delivered over a period of 10 weeks will be delivered by general nurses trained in both treatments. Self-report questionnaire data will be collected at baseline (0 weeks, mid-therapy (week 5 of therapy, post-therapy (15 weeks and at six months (26 weeks and twelve months (52 weeks follow-up. Primary outcomes are distress and MS-related social and role impairment at twelve month follow-up. Analysis will also consider predictors and mechanisms of change during therapy. In-depth interviews to examine participants' experiences of the interventions will be conducted with a purposively sampled sub-set of the trial participants. An economic analysis will also take place. Discussion This trial is distinctive in its aims in that it aids adjustment to MS in a broad sense. It is not a treatment specifically for depression. Use of nurses as therapists makes the interventions potentially viable in terms of being rolled out in the NHS. The trial benefits from incorporating patient input in the development and evaluation stages. The trial will provide important information about the

  3. Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010 in normal dogs

    Directory of Open Access Journals (Sweden)

    Axiak SM

    2011-10-01

    dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m2. Keywords: paclitaxel, nanoparticle, canine

  4. A prospective randomised trial comparing mesh types and fixation in totally extraperitoneal inguinal hernia repairs.

    Science.gov (United States)

    Cristaudo, Adam; Nayak, Arun; Martin, Sarah; Adib, Reza; Martin, Ian

    2015-05-01

    The totally extraperitoneal (TEP) approach for surgical repair of inguinal hernias has emerged as a popular technique. We conducted a prospective randomised trial to compare patient comfort scores using different mesh types and fixation using this technique. Over a 14 month period, 146 patients underwent 232 TEP inguinal hernia repairs. We compared the comfort scores of patients who underwent these procedures using different types of mesh and fixation. A non-absorbable 15 × 10 cm anatomical mesh fixed with absorbable tacks (Control group) was compared with either a non-absorbable 15 × 10 cm folding slit mesh with absorbable tacks (Group 2), a partially-absorbable 15 × 10 cm mesh with absorbable tacks (Group 3) or a non-absorbable 15 × 10 cm anatomical mesh fixed with 2 ml fibrin sealant (Group 4). Outcomes were compared at 1, 2, 4 and 12 weeks using the Carolina Comfort Scale (CCS) scores. At 1, 2, 4 and 12 weeks, the median global CCS scores were low for all treatment groups. Statistically significant differences were seen only for median CCS scores and subscores with the use of partially-absorbable mesh with absorbable tacks (Group 3) at weeks 2 and 4. However, these were no longer significant at week 12. In this study, the TEP inguinal hernia repair with minimal fixation results in low CCS scores. There were no statistical differences in CCS scores when comparing types of mesh, configuration of the mesh or fixation methods. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  5. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

    OpenAIRE

    Kuniaki Tsutsumi; Takanori Kaname; Haruka Shiraishi; Takehiro Kawashiri; Nobuaki Egashira

    2016-01-01

    Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7) and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect th...

  6. Suberoylanilide hydroxamic acid sensitizes neuroblastoma to paclitaxel by inhibiting thioredoxin-related protein 14-mediated autophagy.

    Science.gov (United States)

    Zhen, Zijun; Yang, Kaibin; Ye, Litong; You, Zhiyao; Chen, Rirong; Liu, Ying; He, Youjian

    2017-07-01

    Paclitaxel is not as effective for neuroblastoma as most of the front-line chemotherapeutics due to drug resistance. This study explored the regulatory mechanism of paclitaxel-associated autophagy and potential solutions to paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was detected by scanning transmission electron microscopy and flow cytometry. The autophagy-associated proteins were assessed by western blot. Autophagy was induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and thioredoxin-related protein 14 (TRP14), were found to be upregulated in neuroblastoma cells that were exposed to paclitaxel. The inhibition of Beclin 1 or TRP14 by siRNA increased the sensitivity of the tumor cells to paclitaxel. In addition, Beclin 1-mediated autophagy was regulated by TRP14. Furthermore, the TRP14 inhibitor suberoylanilide hydroxamic acid (SAHA) downregulated paclitaxel-induced autophagy and enhanced the anticancer effects of paclitaxel in normal control cancer cells but not in cells with upregulated Beclin 1 and TRP14 expression. Our findings showed that paclitaxel-induced autophagy in neuroblastoma cells was regulated by TRP14 and that SAHA could sensitize neuroblastoma cells to paclitaxel by specifically inhibiting TRP14. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Gene expression profile of sodium channel subunits in the anterior cingulate cortex during experimental paclitaxel-induced neuropathic pain in mice

    Directory of Open Access Journals (Sweden)

    Willias Masocha

    2016-11-01

    Full Text Available Paclitaxel, a chemotherapeutic agent, causes neuropathic pain whose supraspinal pathophysiology is not fully understood. Dysregulation of sodium channel expression, studied mainly in the periphery and spinal cord level, contributes to the pathogenesis of neuropathic pain. We examined gene expression of sodium channel (Nav subunits by real time polymerase chain reaction (PCR in the anterior cingulate cortex (ACC at day 7 post first administration of paclitaxel, when mice had developed paclitaxel-induced thermal hyperalgesia. The ACC was chosen because increased activity in the ACC has been observed during neuropathic pain. In the ACC of vehicle-treated animals the threshold cycle (Ct values for Nav1.4, Nav1.5, Nav1.7, Nav1.8 and Nav1.9 were above 30 and/or not detectable in some samples. Thus, comparison in mRNA expression between untreated control, vehicle-treated and paclitaxel treated animals was done for Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nax as well as Navβ1–Navβ4. There were no differences in the transcript levels of Nav1.1–Nav1.3, Nav1.6, Nax, Navβ1–Navβ3 between untreated and vehicle-treated mice, however, vehicle treatment increased Navβ4 expression. Paclitaxel treatment significantly increased the mRNA expression of Nav1.1, Nav1.2, Nav1.6 and Nax, but not Nav1.3, sodium channel alpha subunits compared to vehicle-treated animals. Treatment with paclitaxel significantly increased the expression of Navβ1 and Navβ3, but not Navβ2 and Navβ4, sodium channel beta subunits compared to vehicle-treated animals. These findings suggest that during paclitaxel-induced neuropathic pain (PINP there is differential upregulation of sodium channels in the ACC, which might contribute to the increased neuronal activity observed in the area during neuropathic pain.

  8. Comparing the Effectiveness of a Clinical Registry and a Clinical Data Warehouse for Supporting Clinical Trial Recruitment: A Case Study

    Science.gov (United States)

    Weng, Chunhua; Bigger, J Thomas; Busacca, Linda; Wilcox, Adam; Getaneh, Asqual

    2010-01-01

    This paper reports a case study comparing the relative efficiency of using a Diabetes Registry or a Clinical Data Warehouse to recruit participants for a diabetes clinical trial, TECOS. The Clinical Data Warehouse generated higher positive predictive accuracy (31% vs. 6.6%) and higher participant recruitment than the Registry (30 vs. 14 participants) in a shorter time period (59 vs. 74 working days). We identify important factors that increase clinical trial recruitment efficiency and lower cost. PMID:21347102

  9. Comparative costs and activity from a sample of UK clinical trials units.

    Science.gov (United States)

    Hind, Daniel; Reeves, Barnaby C; Bathers, Sarah; Bray, Christopher; Corkhill, Andrea; Hayward, Christopher; Harper, Lynda; Napp, Vicky; Norrie, John; Speed, Chris; Tremain, Liz; Keat, Nicola; Bradburn, Mike

    2017-05-02

    The costs of medical research are a concern. Clinical Trials Units (CTUs) need to better understand variations in the costs of their activities. Representatives of ten CTUs and two grant-awarding bodies pooled their experiences in discussions over 1.5 years. Five of the CTUs provided estimates of, and written justification for, costs associated with CTU activities required to implement an identical protocol. The protocol described a 5.5-year, nonpharmacological randomized controlled trial (RCT) conducted at 20 centres. Direct and indirect costs, the number of full time equivalents (FTEs) and the FTEs attracting overheads were compared and qualitative methods (unstructured interviews and thematic analysis) were used to interpret the results. Four members of the group (funding-body representatives or award panel members) reviewed the justification statements for transparency and information content. Separately, 163 activities common to trials were assigned to roles used by nine CTUs; the consistency of role delineation was assessed by Cohen's κ. Median full economic cost of CTU activities was £769,637 (range: £661,112 to £1,383,323). Indirect costs varied considerably, accounting for between 15% and 59% (median 35%) of the full economic cost of the grant. Excluding one CTU, which used external statisticians, the total number of FTEs ranged from 2.0 to 3.0; total FTEs attracting overheads ranged from 0.3 to 2.0. Variation in directly incurred staff costs depended on whether CTUs: supported particular roles from core funding rather than grants; opted not to cost certain activities into the grant; assigned clerical or data management tasks to research or administrative staff; employed extensive on-site monitoring strategies (also the main source of variation in non-staff costs). Funders preferred written justifications of costs that described both FTEs and indicative tasks for funded roles, with itemised non-staff costs. Consistency in role delineation was fair (κ

  10. Complications and Adverse Events of a Randomized Clinical Trial Comparing 3 Graft Types for ACL Reconstruction.

    Science.gov (United States)

    Mohtadi, Nicholas; Barber, Rhamona; Chan, Denise; Paolucci, Elizabeth Oddone

    2016-05-01

    ). This article reports on the complications/adverse events that were prospectively identified up to 2 years postoperatively, in a defined patient population participating in a large double-blind randomized clinical trial comparing PT, single-bundle hamstring, and DB hamstring reconstructions for ACL rupture.

  11. Porcine dermis compared with polypropylene mesh for laparoscopic sacrocolpopexy: a randomized controlled trial.

    Science.gov (United States)

    Culligan, Patrick J; Salamon, Charbel; Priestley, Jennifer L; Shariati, Amir

    2013-01-01

    To compare the surgical outcomes 12 months after laparoscopic sacrocolpopexy performed with porcine dermis and the current gold standard of polypropylene mesh. Patients scheduled for laparoscopic sacrocolpopexy were eligible for this randomized controlled trial. Both our clinical research nurse and the patients were blinded as to which material was used. Our primary end point was objective anatomic cure defined as no pelvic organ prolapse quantification (POP-Q) points Stage 2 or greater at any postoperative interval. Our sample size calculation called for 57 patients in each group to achieve 90% power to detect a 23% difference in objective anatomic cure at 12 months (α=0.05). Our secondary end point was clinical cure. Any patient with a POP-Q point greater than zero, or Point C less than or equal to -5, or any complaints of prolapse symptoms whatsoever on Pelvic Floor Distress Inventory-20 or Pelvic Floor Impact Questionnaire, Short Form 7, or reoperation for prolapse were considered "clinical failures"; the rest were "clinical cures." Statistical comparisons were performed using the χ or independent samples t test as appropriate. As expected, there were no preoperative differences between the porcine (n=57) and mesh (n=58) groups. The 12-month objective anatomic cure rates for the porcine and mesh groups were 80.7% and 86.2%, respectively (P=.24), and the "clinical cure" rates for the porcine and mesh groups were 84.2% and 89.7%, respectively (P=.96). Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire, Short Form 7 score improvements were significant for both groups with no differences found between groups. There were no major operative complications. There were similar outcomes in subjective or objective results 12 months after laparoscopic sacrocolpopexy performed with either porcine dermis or polypropylene mesh. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00564083. I.

  12. Randomized clinical trial comparing cold knife conization of the cervix with and without lateral hemostatic sutures.

    Science.gov (United States)

    Bueno, Letícia Rossi; Binda, Marcia; Monego, Heleusa; Scherer, Roberta Luísa; Rolim, Karen Machado; Bottini, Alessandra Leal; Fregnani, José H T G; dos Reis, Ricardo

    2015-06-01

    Compare blood loss during cold knife conization of the cervix with and without lateral hemostatic sutures in the cervical branches of the uterine arteries. Randomized clinical trial. Hospital de Clínicas de Porto Alegre (HCPA). 102 patients that underwent cold knife conization. Women that underwent cold knife conization of the cervix were randomized to undergo the procedure with or without lateral hemostatic sutures. blood loss measured in grams. operative time and postoperative intervention. Only the participants were blinded to group assignment. From March 2009 to August 2012, patients were randomly assigned to one of the study groups. There were no differences in amount of blood loss between patients that underwent the procedure with and without sutures (p = 0.39). Operative time was shorter in the group without suture (p = 0.020). There were no differences in intervention due to bleeding (p = 0.20). Blood loss was greater among menstruating women than for menopausal women (p = 0.011). There were no differences in amount of blood lost between smoking and nonsmoking patients (p = 0.082). Lateral hemostatic sutures do not affect the amount of intraoperative bleeding or the number of postoperative interventions. Their use is not necessary because they result in longer operative time, have a higher cost due to the use of suture material and pose the risk of ureter lesion in case the sutures are not placed at a lower position in the cervix. ClinicalTrials. gov identifier: NCT02184975. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  13. Quantitative image analysis of intra-tumoral bFGF level as a molecular marker of paclitaxel resistance

    Directory of Open Access Journals (Sweden)

    Wientjes M Guillaume

    2008-01-01

    Full Text Available Abstract Background The role of basic fibroblast growth factor (bFGF in chemoresistance is controversial; some studies showed a relationship between higher bFGF level and chemoresistance while other studies showed the opposite finding. The goal of the present study was to quantify bFGF levels in archived tumor tissues, and to determine its relationship with chemosensitivity. Methods We established an image analysis-based method to quantify and convert the immunostaining intensity of intra-tumor bFGF to concentrations; this was accomplished by generating standard curves using human xenograft tumors as the renewable tissue source for simultaneous image analysis and ELISA. The relationships between bFGF concentrations and tumor chemosensitivity of patient tumors (n = 87 to paclitaxel were evaluated using linear regression analysis. Results The image analysis results were compared to our previous results obtained using a conventional, semi-quantitative visual scoring method. While both analyses indicated an inverse relationship between bFGF level and tumor sensitivity to paclitaxel, the image analysis method, by providing bFGF levels in individual tumors and therefore more data points (87 numerical values as opposed to four groups of staining intensities, further enabled the quantitative analysis of the relationship in subgroups of tumors with different pathobiological properties. The results show significant correlation between bFGF level and tumor sensitivity to the antiproliferation effect, but not the apoptotic effect, of paclitaxel. We further found stronger correlations of bFGF level and paclitaxel sensitivity in four tumor subgroups (high stage, positive p53 staining, negative aFGF staining, containing higher-than-median bFGF level, compared to all other groups. These findings suggest that the relationship between intra-tumoral bFGF level and paclitaxel sensitivity was context-dependent, which may explain the previous contradictory findings

  14. Comparative efficacy of simultaneous versus sequential multiple health behavior change interventions among adults: A systematic review of randomised trials.

    Science.gov (United States)

    James, Erica; Freund, Megan; Booth, Angela; Duncan, Mitch J; Johnson, Natalie; Short, Camille E; Wolfenden, Luke; Stacey, Fiona G; Kay-Lambkin, Frances; Vandelanotte, Corneel

    2016-08-01

    Growing evidence points to the benefits of addressing multiple health behaviors rather than single behaviors. This review evaluates the relative effectiveness of simultaneous and sequentially delivered multiple health behavior change (MHBC) interventions. Secondary aims were to identify: a) the most effective spacing of sequentially delivered components; b) differences in efficacy of MHBC interventions for adoption/cessation behaviors and lifestyle/addictive behaviors, and; c) differences in trial retention between simultaneously and sequentially delivered interventions. MHBC intervention trials published up to October 2015 were identified through a systematic search. Eligible trials were randomised controlled trials that directly compared simultaneous and sequential delivery of a MHBC intervention. A narrative synthesis was undertaken. Six trials met the inclusion criteria and across these trials the behaviors targeted were smoking, diet, physical activity, and alcohol consumption. Three trials reported a difference in intervention effect between a sequential and simultaneous approach in at least one behavioral outcome. Of these, two trials favoured a sequential approach on smoking. One trial favoured a simultaneous approach on fat intake. There was no difference in retention between sequential and simultaneous approaches. There is limited evidence regarding the relative effectiveness of sequential and simultaneous approaches. Given only three of the six trials observed a difference in intervention effectiveness for one health behavior outcome, and the relatively consistent finding that the sequential and simultaneous approaches were more effective than a usual/minimal care control condition, it appears that both approaches should be considered equally efficacious. PROSPERO registration number: CRD42015027876. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A clinical trial comparing Lanconone® with ibuprofen for rapid relief in acute joint pain.

    Science.gov (United States)

    Girandola, Robert N; Srivastava, Shalini; Loullis, Costas C

    2016-04-06

    To study the effect of Lanconone® (1000 mg) on acute pain on exertion as compared to the standard of care, Ibuprofen (400 mg). The study recruited 72 subjects diagnosed with mild to moderate knee joint pain on exertion. Subjects with Pain Visual Analogue Scale of more than 40 mm were included. Uphill walking was provided as the stressor using Naughton's protocol on a treadmill. The subjects walked for 10 minutes continuously followed by a rest period and baseline pain score for index knee joint was recorded. Subjects were administered a single dose of Lanconone® (1000 mg)/Ibuprofen (400 mg). Thereafter the same stressor was provided at 0.5, 1, 2, 3, 4, and 6 hours, subsequently, pain scores were recorded on a visual analogue scale. Double stopwatch method was used to evaluate the onset of pain relief and time taken to meaningful pain relief. Both Lanconone® and Ibuprofen showed the first perceived pain relief at 65.31 ± 35.57 mins as compared to 60.82 ± 32.56 mins respectively. The mean time taken to experience meaningful pain relief in Lanconone® group was 196.59 ± 70.85 mins compared to 167.13 ± 71.41 mins amongst Ibuprofen group. The meaningful pain relief continued for 6 hours. The current study successfully demonstrated rapid pain-relieving potential of Lanconone® which was comparable to Ibuprofen. No adverse event related to the interventions was reported in the study. Clinical trials.gov NCT02417506 . 21 January 2015.

  16. A randomized controlled trial comparing EMDR and CBT for obsessive-compulsive disorder.

    Science.gov (United States)

    Marsden, Zoe; Lovell, Karina; Blore, David; Ali, Shehzad; Delgadillo, Jaime

    2018-01-01

    This study aimed to evaluate eye movement desensitization and reprocessing (EMDR) as a treatment for obsessive-compulsive disorder (OCD), by comparison to cognitive behavioural therapy (CBT) based on exposure and response prevention. This was a pragmatic, feasibility randomized controlled trial in which 55 participants with OCD were randomized to EMDR (n = 29) or CBT (n = 26). The Yale-Brown obsessive-compulsive scale was completed at baseline, after treatment and at 6 months follow-up. Treatment completion and response rates were compared using chi-square tests. Effect size was examined using Cohen's d and multilevel modelling. Overall, 61.8% completed treatment and 30.2% attained reliable and clinically significant improvement in OCD symptoms, with no significant differences between groups (p > .05). There were no significant differences between groups in Yale-Brown obsessive-compulsive scale severity post-treatment (d = -0.24, p = .38) or at 6 months follow-up (d = -0.03, p = .90). EMDR and CBT had comparable completion rates and clinical outcomes. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Comparing the effects of Calendula officinalis and clotrimazole on vaginal Candidiasis: A randomized controlled trial.

    Science.gov (United States)

    Saffari, Elnaz; Mohammad-Alizadeh-Charandabi, Sakineh; Adibpour, Mohammad; Mirghafourvand, Mojgan; Javadzadeh, Yousef

    2017-01-01

    This triple-blind trial examined the effects of Calendula officinalis vaginal cream on the treatment of vaginal Candidiasis (primary outcome) and sexual function (secondary outcome). Married women aged 18-45 years with vaginal Candidiasis (n = 150) were recruited from April to October 2014 and randomized into Calendula and clotrimazole groups, using 5-g vaginal cream every night for seven nights. Clinical and laboratory assessments were conducted at 10-15 and 30-35 days after intervention and the female sexual function index was assessed at 30-35 days. Six women were lost to follow-up. The frequency of testing negative for Candidiasis in the Calendula group was significantly lower at the first (49% vs. 74%; odds ratio (OR) 0.32; 95% confidence interval (CI) 0.16-0.67) but higher at the second (77% vs. 34%; OR 3.1; 95% CI 1.5-6.2) follow-up compared to the clotrimazole group. The frequency of most signs and symptoms were almost equal in the two groups at the first follow-up, but were significantly lower in the Calendula group at the second follow-up. Sexual function had almost equal significant improvement in both groups. Calendula vaginal cream appears to have been effective in the treatment of vaginal Candidiasis and to have a delayed but greater long-term effect compared to clotrimazole.

  18. Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial.

    Science.gov (United States)

    Niromanesh, Shirin; Alavi, Azin; Sharbaf, Fatemeh Rahimi; Amjadi, Nooshin; Moosavi, Sanaz; Akbari, Soheila

    2012-12-01

    To evaluate the effect of metformin and insulin in glycemic control and compare pregnancy outcome in women with gestational diabetes mellitus (GDM). This randomized controlled trial was conducted in GDM women with singleton pregnancy and gestational age between 20 and 34 weeks who did not achieve glycemic control on diet were assigned randomly to receive either metformin (n=80) or insulin (n=80). The primary outcomes were maternal glycemic control and birth weight. The secondary outcomes were neonatal and obstetric complications. Two groups were comparable regarding the maternal characteristics. Two groups were similar in mean FBS (P=0.68) and postprandial measurements (P=0.87) throughout GDM treatment. The neonates of metformin group had less rate of birth weight centile >90 than insulin group (RR: 0.5, 95% CI: 0.3-0.9, P=0.012). Maternal weight gain was reduced in the metformin group (P0.05). In metformin group 14% of women needed to supplemental insulin to achieve euglycemia. Metformin is an effective and safe alternative treatment to insulin for women with GDM. This study does not show significant risk of maternal or neonatal adverse outcome with the use of metformin. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Oral microemulsions of paclitaxel: in situ and pharmacokinetic studies.

    Science.gov (United States)

    Nornoo, Adwoa O; Zheng, Haian; Lopes, Luciana B; Johnson-Restrepo, Boris; Kannan, Kurunthachalam; Reed, Rachel

    2009-02-01

    The overall goal of this study was to develop cremophor-free oral microemulsions of paclitaxel (PAC) to enhance its permeability and oral absorption. The mechanism of this enhancement, as well as characteristics of the microemulsions relevant to the increase in permeability and absorption of the low solubility, low permeability PAC was investigated. Phase diagrams were used to determine the macroscopic phase behavior of the microemulsions and to compare the efficiency of different surfactant-oil mixtures to incorporate water. The microemulsion region on the phase diagrams utilizing surfactant-myvacet oil combinations was in decreasing order: lecithin: butanol: myvacet oil (LBM, 48.5%)>centromix CPS: 1-butanol: myvacet oil (CPS, 45.15%)>capmul MCM: polysorbate 80: myvacet oil (CPM, 27.6%)>capryol 90: polysorbate 80: myvacet oil (CP-P80, 23.9%)>capmul: myvacet oil (CM, 20%). Oil-in-water (o/w) microemulsions had larger droplet sizes (687-1010 nm) than the water-in-oil (w/o) microemulsions (272-363 nm) when measured using a Zetasizer nano series particle size analyzer. Utilizing nuclear magnetic resonance spectroscopy (NMR), the self-diffusion coefficient (D) of PAC in CM, LBM and CPM containing 10% of deuterium oxide (D(2)O) was 2.24x10(-11), 1.97x10(-11) and 0.51x10(-11) m(2)/s, respectively. These values indicate the faster molecular mobility of PAC in the two w/o microemulsions (CM and LBM) than the o/w microemulsion--CPM. The in situ permeability of PAC through male CD-IGS rat intestine was 3- and 11-fold higher from LBM and CM, respectively, than that from the control clinical formulation, Taxol (CE, cremophor: ethanol) in a single pass perfusion study. PAC permeability was significantly increased in the presence of the pgp/CYP3A4 inhibitor cyclosporine A (CsA). This enhancement may be attributed to the pgp inhibitory effect of the surfactants, oil and/or the membrane perturbation effect of the surfactants. The oral disposition of PAC in CM, LBM and CPM compared

  20. Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs.

    Science.gov (United States)

    Axiak, Sandra M; Selting, Kim A; Decedue, Charles J; Henry, Carolyn J; Tate, Deborah; Howell, Jahna; Bilof, K James; Kim, Dae Y

    2011-01-01

    Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m(2), and subsequent dosages were escalated at 50% (dog 1), 100% (dog 2), or 200% (dog 3) with each cycle, to a maximum of 240 mg/m(2). Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m(2). Grade 1-2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen) toxicity was noted. CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m(2).

  1. Subcutaneous Injection of Adalimumab Trial compared with Control (SCIATiC): a randomised controlled trial of adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica.

    Science.gov (United States)

    Williams, Nefyn H; Jenkins, Alison; Goulden, Nia; Hoare, Zoe; Hughes, Dyfrig A; Wood, Eifiona; Foster, Nadine E; Walsh, David A; Carnes, Dawn; Sparkes, Valerie; Hay, Elaine M; Isaacs, John; Konstantinou, Kika; Morrissey, Dylan; Karppinen, Jaro; Genevay, Stephane; Wilkinson, Clare

    2017-10-01

    Biological treatments such as adalimumab (Humira ® ; AbbVie Ltd, Maidenhead, UK) are antibodies targeting tumour necrosis factor alpha, released from ruptured intervertebral discs, which might be useful in sciatica. Recent systematic reviews concluded that they might be effective, but that a definitive randomised controlled trial was needed. Usual care in the NHS typically includes a physiotherapy intervention. To test whether or not injections of adalimumab plus physiotherapy are more clinically effective and cost-effective than injections of saline plus physiotherapy for patients with sciatica. Pragmatic, parallel-group, randomised controlled trial with blinded participants and clinicians, and an outcome assessment and statistical analysis with concurrent economic evaluation and internal pilot. Participants were referred from primary care and musculoskeletal services to outpatient physiotherapy clinics. Adults with persistent symptoms of sciatica of 1-6 months' duration and with moderate to high levels of disability. Eligibility was assessed by research physiotherapists according to clinical criteria for diagnosing sciatica. After a second eligibility check, trial participants were randomised to receive two doses of adalimumab (80 mg and then 40 mg 2 weeks later) or saline injections. Both groups were referred for a course of physiotherapy. Outcomes were measured at the start, and after 6 weeks' and 6 months' follow-up. The main outcome measure was the Oswestry Disability Index (ODI). Other outcomes: leg pain version of the Roland-Morris Disability Questionnaire, Sciatica Bothersomeness Index, EuroQol-5 Dimensions, 5-level version, Hospital Anxiety and Depression Scale, resource use, risk of persistent disabling pain, pain trajectory based on a single question, Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia and adverse effects. To detect an effect size of 0.4 with 90% power, a 5% significance level for a two-tailed t -test and 80% retention

  2. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment

    OpenAIRE

    Mo, Michelle; Erdelyi, Ildiko; Szigeti-Buck, Klara; Benbow, Jennifer H.; Ehrlich, Barbara E.

    2012-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that occurs in many patients undergoing chemotherapy. It is often irreversible and frequently leads to early termination of treatment. In this study, we have identified two compounds, lithium and ibudilast, that when administered as a single prophylactic injection prior to paclitaxel treatment, prevent the development of CIPN in mice at the sensory-motor and cellular level. The prevention of neuropathy was not obs...

  3. Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole.

    Science.gov (United States)

    Rose-Nussbaumer, Jennifer; Prajna, N Venkatesh; Krishnan, Tiruvengada; Mascarenhas, Jeena; Rajaraman, Revathi; Srinivasan, Muthiah; Raghavan, Anita; Oldenburg, Catherine E; O'Brien, Kieran S; Ray, Kathryn J; Porco, Travis C; McLeod, Stephen D; Acharya, Nisha R; Keenan, Jeremy D; Lietman, Thomas M

    2016-07-01

    The Mycotic Ulcer Treatment Trial I (MUTT I) was a double-masked, multicentre, randomised controlled trial, which found that topical natamycin is superior to voriconazole for the treatment of filamentous fungal corneal ulcers. In this study, we determine risk factors for low vision-related quality of life in patients with fungal keratitis. The Indian visual function questionnaire (IND-VFQ) was administered to MUTT I study participants at 3 months. Associations between patient and ulcer characteristics and IND-VFQ subscale score were assessed using generalised estimating equations. 323 patients were enrolled in the trial, and 292 (90.4%) completed the IND-VFQ at 3 months. Out of a total possible score of 100, the average VFQ score for all participants was 81.3 (range 0-100, SD 23.6). After correcting for treatment arm, each logMAR line of worse baseline visual acuity in the affected eye resulted in an average 1.2 points decrease on VFQ at 3 months (95% CI -1.8 to 0.6, p<0.001). Those who required therapeutic penetrating keratoplasty had an average of 25.2 points decrease on VFQ after correcting for treatment arm (95% CI -31.8 to -18.5, p<0.001). Study participants who were unemployed had on average 28.5 points decrease on VFQ (95% CI -46.9 to -10.2, p=0.002) after correcting for treatment arm. Monocular vision loss from corneal opacity due to fungal keratitis reduced vision-related quality of life. Given the relatively high worldwide burden of corneal opacity, improving treatment outcomes of corneal infections should be a public health priority. Clinicaltrials.gov Identifier: NCT00996736. 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/.

  4. Development and evaluation of targeting ligands surface modified paclitaxel nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jeong Sun [Division of Undeclared Majors, Chosun University, Gwangju 501-759 (Korea, Republic of); Yoon, Doo-Soo; Sohn, Jun Youn [Department of Bioenvironmental & Chemical Engineering, Chosun College of Science & Technology, Gwangju 501-744 (Korea, Republic of); Park, Jeong-Sook, E-mail: eicosa@cnu.ac.kr [College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Choi, Jin-Seok, E-mail: c34281@gmail.com [College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of)

    2017-03-01

    To overcome the toxicity of excipient or blank nanoparticles for drug delivery nano-system, the surface modified paclitaxel nanocrystals (PTX-NC) have been developed. PTX-NCs were prepared by nano-precipitation method. The surface of PTX-NCs were modified by grafting with apo-transferrin (Tf) or hyaluronic acid (HA). The physical properties of PTX-NCs were evaluated by field emission scanning electron microscope (FE-SEM), zeta-sizer, zeta-potential, differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectrometry. In vitro drug release study was performed in phosphate buffered saline (PBS) with or without 0.5% (w/v) Tween 80 for 24 h. Cellular uptake was studied at time intervals of 0.5, 1, and 2 h in MCF-7 cells, and cell growth inhibition study was performed for 24 h using MCF-7 cells (cancer cells), and HaCaT cells (normal cells). Three different types of PTX-NCs with a mean size of 236.0 ± 100.6 nm (PTX-NC), 302.0 ± 152.0 nm (Tf-PTX-NC) and 339 ± 180.6 nm (HA-PTX-NC) were successfully prepared. The drug release profiles showed 29.1%/6.9% (PTX (pure)), 40.7%/23.9% (PTX-NC), 50.5%/25.1% (Tf-PTX-NC) and 46.8/24.8% (HA-PTX-NC) in PBS with/without 0.5% (w/v) Tween 80 for 24 h, respectively. As per the results, the drug release of PTX-NCs showed the faster release as compared to that of PTX (pure). Surface modified PTX-NCs exhibited higher values for cell permeability than unmodified PTX-NC in the cellular uptake study. Surface modified PTX-NCs inhibited the cell growth approximately to 60% in MCF-7 cells, however effect of surface modified PTX-NCs on normal cell line was lower than the PTX-NC and PTX (pure). In conclusion, biological macromolecules (Tf or HA) surface modified PTX-NC enhanced the cellular uptake and the cell growth inhibition. - Highlights: • Surface modified PTX-NCs with HA and Tf are successfully prepared by adsorption method. • Enhanced cellular uptake of modified PTX-NCs compared to unmodified PTX-NC • Improved

  5. Effect of paclitaxel (TAXOL) alone and in combination with radiation on the gastrointestinal mucosa

    International Nuclear Information System (INIS)

    Mason, K.A.; Milas, L.; Peters, L.J.

    1995-01-01

    Paclitaxel is a potentially useful drug for augmenting the cytotoxic action of radiotherapy because it has independent cytotoxic activity against certain cancers and blocks cells in the radiosensitive mitotic phase of the cell cycle. However, all rapidly proliferating tissues, both normal and neoplastic, may be affected by this therapeutic strategy. The aim of this study was to define the in vivo response of rapidly dividing cells of the small bowel mucosa in mice to paclitaxel given alone and in combination with radiation. Paclitaxel blocked jejunal crypt cells in mitosis and induced apoptosis in a dose-dependent manner. Fractionating the paclitaxel dose over 1-4 days did not result in any greater accumulation of mitotically blocked cells than did a single dose. Mitosis peaked 2-4 h after paclitaxel and returned to near normal by 24 h. Apoptosis lagged several hours behind mitosis and peaked about 6 h later than mitosis. Despite these kinetic perturbations, there was little or no enhancement of radiation effect when single doses were delivered 2-4 h after paclitaxel administration. The maximum sensitizer enhancement ratio of 1.07 observed after a single paclitaxel dose of 40 mg/kg is consistent with independent crypt cell killing. Conversely, when radiation was given 24 h after paclitaxel, a significant protective effect of the drug (SER 0.89-0.92), most probably due to a regenerative overshoot induced by paclitaxel, was observed. Stem cells of the jejunal mucosa determining radiation response were not radiosensitized by paclitaxel with the drug concentrations and dose deliver schedules used, although additive cytotoxicity was observed with the highest drug dose. A radioprotective effect was observed when radiation was given 24 h after paclitaxel administration. 33 refs., 4 figs., 3 tabs

  6. 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

  7. Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions.

    Science.gov (United States)

    Johns, Claire; Seav, Susan M; Dominick, Sally A; Gorman, Jessica R; Li, Hongying; Natarajan, Loki; Mao, Jun James; Irene Su, H

    2016-04-01

    Patient-centered decision making about hot flash treatments often incorporates a balance of efficacy and side effects in addition to patient preference. This systematic review examines randomized controlled trials (RCTs) comparing at least two non-hormonal hot flash treatments in breast cancer survivors. In July 2015, PubMed, SCOPUS, CINAHL, Cochrane, and Web of Science databases were searched for RCTs comparing active, non-hormonal hot flash treatments in female breast cancer survivors. Thirteen trials were included after identifying 906 potential studies. Four trials were dose comparison studies of pharmacologic treatments citalopram, venlafaxine, gabapentin, and paroxetine. Hot flash reduction did not differ by tamoxifen or aromatase inhibitor use. Citalopram 10, 20, and 30 mg daily had comparable outcomes. Venlafaxine 75 mg daily improved hot flashes without additional side effects from higher dosing. Gabapentin 900 mg daily improved hot flashes more than 300 mg. Paroxetine 10 mg daily had fewer side effects than 20 mg. Among four trials comparing different pharmacologic treatments, venlafaxine alleviated hot flash symptoms faster than clonidine; participants preferred venlafaxine over gabapentin. Five trials compared pharmacologic to non-pharmacologic treatments. Acupuncture had similar efficacy to venlafaxine and gabapentin but may have longer durability after completing treatment and fewer side effects. We could not perform a pooled meta-analysis because outcomes were not reported in comparable formats. Clinical trial data on non-hormonal hot flash treatments provide comparisons of hot flash efficacy and other patient important outcomes to guide clinical management. Clinicians can use the information to help patients select hot flash interventions.

  8. Randomised trial comparing hysterectomy with endometrial ablation for dysfunctional uterine bleeding: psychiatric and psychosocial aspects.

    Science.gov (United States)

    Alexander, D. A.; Naji, A. A.; Pinion, S. B.; Mollison, J.; Kitchener, H. C.; Parkin, D. E.; Abramovich, D. R.; Russell, I. T.

    1996-01-01

    OBJECTIVE: To compare in psychiatric and psychosocial terms the outcome of hysterectomy and endometrial ablation for the treatment of dysfunctional uterine bleeding. DESIGN: Prospective randomised controlled trial. SETTING--Obstetrics and gynaecology department of a large teaching hospital. SUBJECTS: 204 women with dysfunctional bleeding for whom hysterectomy would have been the preferred treatment were recruited over 24 months and randomly allocated to hysterectomy (99 women) or to hysteroscopic surgery (transcervical resection (52 women) or laser ablation (53 women). MAIN OUTCOME MEASURES: Mental state, martial relationship, psychosocial and sexual adjustment in assessments conducted before the operation and one month, six months, and 12 months later. RESULTS: Both treatments significantly reduced the anxiety and depression present before the operation, and there were no differences in mental health between the groups at 12 months. Hysterectomy did not lead to postoperative psychiatric illness. Sexual interest after the operation did not vary with treatment. Overall, 46 out of 185 (25%) women reported a loss sexual interest and 50 out of 185 (27%) reported increased sexual interest. Marital relationships were unaffected by surgery. Personality and duration of dysfunctional uterine bleeding played no significant part in determining outcome. CONCLUSIONS: Hysteroscopic surgery and hysterectomy have a similar effect on psychiatric and psychosocial outcomes. There is no evidence that hysterectomy leads to postoperative psychiatric illness. PMID:8611783

  9. Randomized trial of a smartphone mobile application compared to text messaging to support smoking cessation.

    Science.gov (United States)

    Buller, David B; Borland, Ron; Bettinghaus, Erwin P; Shane, James H; Zimmerman, Donald E

    2014-03-01

    Text messaging has successfully supported smoking cessation. This study compares a mobile application with text messaging to support smoking cessation. Young adult smokers 18-30 years old (n = 102) participated in a randomized pretest-posttest trial. Smokers received a smartphone application (REQ-Mobile) with short messages and interactive tools or a text messaging system (onQ), managed by an expert system. Self-reported usability of REQ-Mobile and quitting behavior (quit attempts, point-prevalence, 30-day point-prevalence, and continued abstinence) were assessed in posttests. Overall, 60% of smokers used mobile services (REQ-Mobile, 61%, mean of 128.5 messages received; onQ, 59%, mean of 107.8 messages), and 75% evaluated REQ-Mobile as user-friendly. A majority of smokers reported being abstinent at posttest (6 weeks, 53% of completers; 12 weeks, 66% of completers [44% of all cases]). Also, 37% (25%of all cases) reported 30-day point-prevalence abstinence, and 32% (22% of all cases) reported continuous abstinence at 12 weeks. OnQ produced more abstinence (ptext messaging. Text messaging may work better because it is simple, well known, and delivered to a primary inbox. These advantages may disappear as smokers become more experienced with new handsets. Mobile phones may be promising delivery platforms for cessation services using either smartphone applications or text messaging.

  10. Troxipide in the Management of Gastritis: A Randomized Comparative Trial in General Practice

    Directory of Open Access Journals (Sweden)

    Bhupesh Dewan

    2010-01-01

    Full Text Available Background. A trial of empirical acid-suppressive therapy is the usual practice for most patients with symptoms of gastritis in primary care. Aim. To assess the relative efficacy of Troxipide and Ranitidine in patients with endoscopic gastritis over a four-week period. Methods. In all, 142 patients were randomized to Troxipide (100 mg tid or Ranitidine (150 mg bid for a period of four weeks. The severity of the signs of endoscopic gastritis at baseline and week 4 using a four-point scale and the subjective symptom severity at baseline and week 2 & week 4 using a Visual analog scale (VAS were documented. Results. Troxipide was found to be superior to Ranitidine for both, the complete resolution and improvement of endoscopic gastritis. Higher proportion of patients showed complete healing of erosions (88.14%, oozing (96.77%, and edema (93.88% with Troxipide as compared to Ranitidine (<.01. Patients receiving Troxipide also showed a greater improvement in the VAS scores for abdominal pain, bloating, and heartburn (<.01. Both the drugs were found to be well tolerated. Conclusion. In patients with endoscopic gastritis, Troxipide, with its superior rate of improvement, resolution of signs, and subjective clinical symptoms, can be considered as an alternative to the commonly used antisecretory agents.

  11. Prospective controlled trial comparing colostomy irrigation with "spontaneous-action" method.

    Science.gov (United States)

    Williams, N S; Johnston, D

    1980-07-12

    Thirty randomly selected patients with permanent colostomies entered a prospective controlled trial comparing colostomy irrigation with spontaneous action. Each patient was interviewed and examined before irrigation was begun and again after the technique had been used for three months. Each then reverted to spontaneous action for a further three months and was then reassessed. Eight patients abandoned irrigation and 22 (73%) adhered to the protocol. Irrigation caused no mishaps or complications. The mean time spent managing the stoma was 45 +/- SEM 9 min/24 hours during spontaneous action and 53 +/- 9 min/24 hours during irrigation. This difference was not significant. The numbers of bowel actions weekly were 13 +/ SEM 2 during spontaneous action and 6 +/- 1 during irrigation (p Irrigation reduced odour and flatus in 20 patients and enabled 12 out of 18 to stop using drugs and seven to discard their appliance. Irrigation also improved the social life of 18 patients and the working conditions of eight out of 14. These finding show that some patients may not be suitable for irrigation but that for many it is better than the conventional British method of colostomy management. With modern apparatus the technique is safe.

  12. Explaining feast or famine in randomized field trials. Medical science and criminology compared.

    Science.gov (United States)

    Shepherd, Jonathan P

    2003-06-01

    A feast of randomized controlled trials (RCTs) in medical science and comparative famine in criminology can be explained in terms of cultural and structural factors. Of central importance is the context in which the evaluation of interventions is done and the difference in status of situational research in the two disciplines. Evaluation of medical interventions has traditionally been led by practitioner (clinical) academics. This is not the case in criminal justice, where theory has had higher status than intervention research. Medical science has advanced in, or closely associated with, university teaching hospitals, but links between criminology and criminal justice services are far more tenuous. The late development of situational crime prevention seems extraordinary from a medical perspective, as does the absence of university police schools in the United Kingdom and elsewhere. These structural and cultural factors explain concentration of expectation, resource, and RCT productivity in medical science. The Campbell Collaboration and the Academy of Experimental Criminology are forces which are reducing this polarization of feast and famine in RCTs. But unless scientific criminology is embedded in university schools which are responsible for the education and training of law, probation, and police practitioners, convergence in terms of RCTs and implementation of findings in practice seems unlikely.

  13. A Randomized Controlled Trial Comparing the Letter Project Advance Directive to Traditional Advance Directive.

    Science.gov (United States)

    Periyakoil, Vyjeyanthi S; Neri, Eric; Kraemer, Helena

    2017-09-01

    Simpler alternatives to traditional advance directives that are easy to understand and available in multiple formats and can be initiated by patients and families will help facilitate advance care planning. The goal of this study was to compare the acceptability of the letter advance directive (LAD) to the traditional advance directive (TAD) of the state of California. A web-based, randomized controlled trial was conducted, in which the participants were randomized to one of two types of advance directives (ADs): the LAD (intervention) or the TAD (control). Primary outcomes were participant ratings of the ease, value, and their level of comfort in the AD document they completed. A total of 400 participants completed the study, with 216 randomized to the LAD and 184 to the TAD by a computerized algorithm. Overall, participants preferred the LAD to the TAD (success rate difference [SRD] = 0.46, 95th percentile confidence interval [CI]: 0.36-0.56, p advance directive to be a better alternative to the traditional advance directive form.

  14. Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2.

    Science.gov (United States)

    Ganz, Patricia A; Romond, Edward H; Cecchini, Reena S; Rastogi, Priya; Geyer, Charles E; Swain, Sandra M; Jeong, Jong-Hyeon; Fehrenbacher, Louis; Gross, Howard M; Brufsky, Adam M; Flynn, Patrick J; Wahl, Tanya A; Seay, Thomas E; Wade, James L; Biggs, David D; Atkins, James N; Polikoff, Jonathan; Zapas, John L; Mamounas, Eleftherios P; Wolmark, Norman

    2017-12-10

    Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment. Patients and Methods Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2-positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions. Results At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a > 10% decline in left ventricular ejection fraction from baseline to a value < 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab. Conclusion In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function.

  15. Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial.

    Science.gov (United States)

    Wang, Chenchen; Schmid, Christopher H; Fielding, Roger A; Harvey, William F; Reid, Kieran F; Price, Lori Lyn; Driban, Jeffrey B; Kalish, Robert; Rones, Ramel; McAlindon, Timothy

    2018-03-21

    To determine the effectiveness of tai chi interventions compared with aerobic exercise, a current core standard treatment in patients with fibromyalgia, and to test whether the effectiveness of tai chi depends on its dosage or duration. Prospective, randomized, 52 week, single blind comparative effectiveness trial. Urban tertiary care academic hospital in the United States between March 2012 and September 2016. 226 adults with fibromyalgia (as defined by the American College of Rheumatology 1990 and 2010 criteria) were included in the intention to treat analyses: 151 were assigned to one of four tai chi groups and 75 to an aerobic exercise group. Participants were randomly assigned to either supervised aerobic exercise (24 weeks, twice weekly) or one of four classic Yang style supervised tai chi interventions (12 or 24 weeks, once or twice weekly). Participants were followed for 52 weeks. Adherence was rigorously encouraged in person and by telephone. The primary outcome was change in the revised fibromyalgia impact questionnaire (FIQR) scores at 24 weeks compared with baseline. Secondary outcomes included changes of scores in patient's global assessment, anxiety, depression, self efficacy, coping strategies, physical functional performance, functional limitation, sleep, and health related quality of life. FIQR scores improved in all five treatment groups, but the combined tai chi groups improved statistically significantly more than the aerobic exercise group in FIQR scores at 24 weeks (difference between groups=5.5 points, 95% confidence interval 0.6 to 10.4, P=0.03) and several secondary outcomes (patient's global assessment=0.9 points, 0.3 to 1.4, P=0.005; anxiety=1.2 points, 0.3 to 2.1, P=0.006; self efficacy=1.0 points, 0.5 to 1.6, P=0.0004; and coping strategies, 2.6 points, 0.8 to 4.3, P=0.005). Tai chi treatment compared with aerobic exercise administered with the same intensity and duration (24 weeks, twice weekly) had greater benefit (between group

  16. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life.

    Science.gov (United States)

    Palumbo, Raffaella; Sottotetti, Federico; Trifirò, Giuseppe; Piazza, Elena; Ferzi, Antonella; Gambaro, Anna; Spinapolice, Elena Giulia; Pozzi, Emma; Tagliaferri, Barbara; Teragni, Cristina; Bernardo, Antonio

    2015-01-01

    A prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC). Fifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m(2) as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal. All of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%-61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52-86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0-11.6 months, range 5-21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment. Our results showed that single-agent nab-paclitaxel 260 mg/m(2) every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that 'difficult to

  17. Raisins compared with other snack effects on glycemia and blood pressure: a randomized, controlled trial.

    Science.gov (United States)

    Anderson, James W; Weiter, Kathy M; Christian, Amber L; Ritchey, Michelle B; Bays, Harold E

    2014-01-01

    To compare effects of raisin snacks with conventional snacks on glycemia and cardiovascular risk factors. A 12-week, randomized, controlled trial compared 3-times-a-day consumption of raisins with intake of processed snacks on glycemia and cardiovascular risk factors. Men and women were randomized to snacks (n = 15) or raisins (n = 31). Outcome measures were performed at baseline, 4, 8, and 12 weeks. Fasting plasma glucose levels were not significantly affected by intake of raisins or snacks. Mean subject post prandial glucose levels were significantly reduced by raisin intake at 12 weeks; changes with raisin intake were -13.1 mg/dL (P = 0.003 vs baseline; P = 0.03 vs snacks). Eating raisins significantly decreased glycated hemoglobin (HbA1c) level (-0.12%; P = 0.004), a significantly greater level decrease than seen with snack intake (P = 0.036). Snack intake did not significantly affect subject systolic or diastolic blood pressure (BP). Raisin intake was associated with reductions in systolic blood pressure (SBP) at 4, 8, and 12 weeks with mean changes of -6.0 to 10.2 mmHg; all these changes were statistically significant (P = 0.015 to 0.001). Raisins were associated with significantly greater changes in diastolic blood pressure (DBP) at 4, 8, and 12 weeks than snacks (P < 0.05). Body weight did not significantly change within or between groups. Regular consumption of raisins may reduce glycemia and cardiovascular risk factors, including BP rate.

  18. End-tidal control vs. manually controlled minimal-flow anesthesia: a prospective comparative trial.

    Science.gov (United States)

    Wetz, A J; Mueller, M M; Walliser, K; Foest, C; Wand, S; Brandes, I F; Waeschle, R M; Bauer, M

    2017-11-01

    To ensure safe general anesthesia, manually controlled anesthesia requires constant monitoring and numerous manual adjustments of the gas dosage, especially for low- and minimal-flow anesthesia. Oxygen flow-rate and administration of volatile anesthetics can also be controlled automatically by anesthesia machines using the end-tidal control technique, which ensures constant end-tidal concentrations of oxygen and anesthetic gas via feedback and continuous adjustment mechanisms. We investigated the hypothesis that end-tidal control is superior to manually controlled minimal-flow anesthesia (0.5 l/min). In this prospective trial, we included 64 patients undergoing elective surgery under general anesthesia. We analyzed the precision of maintenance of the sevoflurane concentration (1.2-1.4%) and expiratory oxygen (35-40%) and the number of necessary adjustments. Target-concentrations of sevoflurane and oxygen were maintained at more stable levels with the use of end-tidal control (during the first 15 min 28% vs. 51% and from 15 to 60 min 1% vs. 19% deviation from sevoflurane target, P tidal oxygen (5, IQR 3-6). The target-concentrations were reached earlier with the use of end-tidal compared with manual controlled minimal-flow anesthesia but required slightly greater use of anesthetic agents (6.9 vs. 6.0 ml/h). End-tidal control is a superior technique for setting and maintaining oxygen and anesthetic gas concentrations in a stable and rapid manner compared with manual control. Consequently, end-tidal control can effectively support the anesthetist. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Randomized controlled trial comparing esophageal dilation to no dilation among adults with esophageal eosinophilia and dysphagia.

    Science.gov (United States)

    Kavitt, R T; Ates, F; Slaughter, J C; Higginbotham, T; Shepherd, B D; Sumner, E L; Vaezi, M F

    2016-11-01

    The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy. © 2015 International Society for Diseases of the Esophagus.

  20. Data extraction from machine-translated versus original language randomized trial reports: a comparative study.

    Science.gov (United States)

    Balk, Ethan M; Chung, Mei; Chen, Minghua L; Chang, Lina Kong Win; Trikalinos, Thomas A

    2013-11-07

    Google Translate offers free Web-based translation, but it is unknown whether its translation accuracy is sufficient to use in systematic reviews to mitigate concerns about language bias. We compared data extraction from non-English language studies with extraction from translations by Google Translate of 10 studies in each of five languages (Chinese, French, German, Japanese and Spanish). Fluent speakers double-extracted original-language articles. Researchers who did not speak the given language double-extracted translated articles along with 10 additional English language trials. Using the original language extractions as a gold standard, we estimated the probability and odds ratio of correctly extracting items from translated articles compared with English, adjusting for reviewer and language. Translation required about 30 minutes per article and extraction of translated articles required additional extraction time. The likelihood of correct extractions was greater for study design and intervention domain items than for outcome descriptions and, particularly, study results. Translated Spanish articles yielded the highest percentage of items (93%) that were correctly extracted more than half the time (followed by German and Japanese 89%, French 85%, and Chinese 78%) but Chinese articles yielded the highest percentage of items (41%) that were correctly extracted >98% of the time (followed by Spanish 30%, French 26%, German 22%, and Japanese 19%). In general, extractors' confidence in translations was not associated with their accuracy. Translation by Google Translate generally required few resources. Based on our analysis of translations from five languages, using machine translation has the potential to reduce language bias in systematic reviews; however, pending additional empirical data, reviewers should be cautious about using translated data. There remains a trade-off between completeness of systematic reviews (including all available studies) and risk of

  1. CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials.

    Science.gov (United States)

    Patrick, Kevin; Wolszon, Laura; Basen-Engquist, Karen M; Demark-Wahnefried, Wendy; Prokhorov, Alex V; Barrera, Stephanie; Baru, Chaitan; Farcas, Emilia; Krueger, Ingolf; Palmer, Doug; Raab, Fred; Rios, Phil; Ziftci, Celal; Peterson, Susan

    2011-03-01

    Improved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of knowledge about patients' lifestyle behaviors that may affect cancer's progression and recurrence, and limited ability to compile and interpret the wide range of variables that must be considered in the cancer treatment. This lack of data integration limits the potential for patients and clinicians to engage in fully informed decision-making regarding cancer prevention, treatment, and survivorship care, and the translation of research results into mainstream medical care. Particularly important, as noted in a 2009 report on CER to the President and Congress, the limited focus on health behavior-change interventions was a major hindrance in this research landscape (DHHS 2009). This paper describes an initiative to improve CER for cancer by addressing several of these limitations. The Cyberinfrastructure for Comparative Effectiveness Research (CYCORE) project, informed by the National Science Foundation's 2007 report "Cyberinfrastructure Vision for 21(st) Century Discovery" has, as its central aim, the creation of a prototype for a user-friendly, open-source cyberinfrastructure (CI) that supports acquisition, storage, visualization, analysis, and sharing of data important for cancer-related CER. Although still under development, the process of gathering requirements for CYCORE has revealed new ways in which CI design can significantly improve the collection and analysis of a wide variety of data types, and has resulted in new and important partnerships among cancer researchers engaged in

  2. The IDvIP trial: a two-centre randomised double-blind controlled trial comparing intramuscular diamorphine and intramuscular pethidine for labour analgesia.

    Science.gov (United States)

    Wee, Michael Y K; Tuckey, Jenny P; Thomas, Peter; Burnard, Sara

    2011-07-08

    Intramuscular pethidine is routinely used throughout the UK for labour analgesia. Studies have suggested that pethidine provides little pain relief in labour and has a number of side effects affecting mother and neonate. It can cause nausea, vomiting and dysphoria in mothers and can cause reduced fetal heart rate variability and accelerations. Neonatal effects include respiratory depression and impaired feeding. There are few large studies comparing the relative side effects and efficacy of different opioids in labour. A small trial comparing intramuscular pethidine with diamorphine, showed diamorphine to have some benefits over pethidine when used for labour analgesia but the study did not investigate the adverse effects of either opioid. The Intramuscular Diamorphine versus Intramuscular Pethidine (IDvIP) trial is a randomised double-blind two centre controlled trial comparing intramuscular diamorphine and pethidine regarding their analgesic efficacy in labour and their side effects in mother, fetus and neonate. Information about the trial will be provided to women in the antenatal period or in early labour. Consent and recruitment to the trial will be obtained when the mother requests opioid analgesia. The sample size requirement is 406 women with data on primary outcomes. The maternal primary outcomes are pain relief during the first 3 hours after trial analgesia and specifically pain relief after 60 minutes. The neonatal primary outcomes are need for resuscitation and Apgar Score analgesia, whether method of analgesia would be used again, use of Entonox, umbilical arterial and venous pH, fetal heart rate, meconium staining, time from delivery to first breath, Apgar scores at 5 mins, naloxone requirement, transfer to neonatal intensive care unit, neonatal haemoglobin oxygen saturation at 30, 60, 90, and 120 mins after delivery, and neonatal sedation and feeding behaviour during first 2 hours. If the trial demonstrates that diamorphine provides better analgesia

  3. Clinical efficacy of paclitaxel in the treatment of mid-stage and ...

    African Journals Online (AJOL)

    Conclusion: Paclitaxel has a significant effect when used to treat mid-stage and advanced gastric cancer. Moreover, additional nursing not only enhances the therapeutic effect but also improves prognosis and quality-of-life. Keywords: Paclitaxel, Mid-stage/advanced cancer, Gastric cancer, Nursing efficacy, Karnofsky ...

  4. Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish.

    Science.gov (United States)

    Lisse, Thomas S; Middleton, Leah J; Pellegrini, Adriana D; Martin, Paige B; Spaulding, Emily L; Lopes, Olivia; Brochu, Elizabeth A; Carter, Erin V; Waldron, Ashley; Rieger, Sandra

    2016-04-12

    Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up-regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions.

  5. CYP3A4*22 genotype and systemic exposure affect paclitaxel-induced neurotoxicity

    NARCIS (Netherlands)

    A.J.M. de Graan (Anne-Joy); L. Elens (Laure); J.A. Sprowl (Jason); A. Sparreboom (Alex); L.E. Friberg (Lena); B. van der Holt (Bronno); P.J. de Raaf (Pleun); P. de Bruijn (Peter); F.K. Engels (Frederike); F.A.L.M. Eskens (Ferry); E.A.C. Wiemer (Erik); J. Verweij (Jaap); A.H.J. Mathijssen (Ron); R.H.N. van Schaik (Ron)

    2013-01-01

    textabstractPurpose: Paclitaxel is used for the treatment of several solid tumors and displays a high interindividual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side effects of paclitaxel. This study explores potential predictive pharmacokinetic and

  6. Peripheral neuropathy due to therapy with paclitaxel, gemcitabine, and cisplatin in patients with advanced ovarian cancer.

    NARCIS (Netherlands)

    Verstappen, C.C.P.; Postma, T.J.; Hoekman, K.; Heimans, J.J.

    2003-01-01

    BACKGROUND: To evaluate the peripheral neuropathic changes induced by combination chemotherapy including paclitaxel (taxol), gemcitabine and cisplatin (TGC regimen). PATIENTS AND METHODS: Eighteen patients with primary or recurrent ovarian cancer were treated with paclitaxel 150 or 110 mg/m2,

  7. In-vitro release of anti-proliferative paclitaxel from novel balloon-expandable polycaprolactone stents

    International Nuclear Information System (INIS)

    Liu, Shih-Jung; Hsiao, Chao-Ying; Chen, Jan-Kan; Liu, Kuo-Sheng; Lee, Cheng-Hung

    2011-01-01

    This report investigated the in-vitro release characteristics of paclitaxel from novel balloon-expandable polycaprolactone stents. Polycaprolactone stents were first manufactured by a lab-made micro-injection molding machine. Paclitaxel and polylactide-polyglycolide (PLGA) copolymer were dissolved in acetonitrile and were coated onto the surface of the stents by a spray coating device, which was designed and built especially for this study. An elution method was utilized to characterize the in-vitro release characteristics of paclitaxel. The high performance liquid chromatography (HPLC) analysis showed that biodegradable stents could provide sustained release of paclitaxel for more than 70 days. Various process parameters that controlled the release rate of paclitaxel were studied. The experimental results suggested that the total period of drug release could be prolonged by adopting 75:25 PLGA copolymers, employing multi-layer coatings, and increasing the drug loading. In addition, the effectiveness of eluted paclitaxel on cell behavior was examined. The results showed that the eluted drug could effectively inhibit the proliferation of smooth muscle cells. - Research Highlights: → We investigate the in-vitro release characteristics of paclitaxel from polycaprolactone stents. → Biodegradable stents provide sustained release of paclitaxel for more than 70 days. → The eluted drug effectively inhibits the proliferation of smooth muscle cells.

  8. Paclitaxel prodrugs, method for preparation as well as their use in selective chemotherapy

    NARCIS (Netherlands)

    de Bont, Hendricus BA; Leenders, Ruben GG; Scheeren, Johan W; Haisma, Hidde J; de Vos, Dick

    1998-01-01

    A paclitaxel prodrug has a paclitaxel portion coupled to a cleavable N-(aliphatic or aromatic)-O-glycosyl carbamate spacer group, and can be administered orally, topically or by injection to provide an anti-tumor effect, the prodrug being activated by a hydrolizing enzyme, an endogeneous enzyme or

  9. Phase II study of radiotherapy with three-dimensional conformal boost concurrent with paclitaxel and cisplatin for Stage IIIB non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Young Seok; Yoon, Sang Min; Choi, Eun Kyung; Yi, Byong Yong; Kim, Jong Hoon; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Lee, Jung Shin; Suh, Cheolwon; Kim, Sang-We; Kim, Dong Soon; Kim, Woo Sung; Park, Heon Joo; Park, Charn Il

    2005-01-01

    Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy with paclitaxel/cisplatin for Stage IIIB locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Radiotherapy was administered to a total dose of 70.2 Gy (daily fraction of 1.8 Gy, 5 days/wk), over an 8-week period, combined with chemotherapy. The chemotherapy consisted of weekly 40 mg/m 2 of paclitaxel plus 20 mg/m 2 of cisplatin for 8 consecutive weeks. All patients received three-dimensional conformal radiotherapy (3D-CRT), based on computed tomography simulated planning after 41.4 Gy. The median follow-up period of survivors was 24 months. Results: Between January 2000 and October 2002, 135 patients with a median age of 60 years were enrolled and analyzed in this prospective trial. The overall response rate was 75% including 2 cases of complete response. The major patterns of failure were local failure and distant metastasis. The 2-year overall and progression-free survival rates were 37% and 18%, respectively. The median overall and progression-free survival times were 17 months and 9 months, respectively. Hematologic toxicity >Grade 2 was observed in 19% of patients and severe non-hematologic toxicity was infrequent. Conclusions: Three-dimensional conformal radiotherapy, combined with paclitaxel and cisplatin chemotherapy, was associated with a satisfactory outcome with manageable toxicity. Further investigations are needed to improve the local control

  10. Re-irradiation with 36 Gy (1.5 Gy Twice Daily) Plus Paclitaxel for Advanced Recurrent and Previously Irradiated SCCHN is Feasible.

    Science.gov (United States)

    Rades, Dirk; Bartscht, Tobias; Idel, Christian; Hakim, Samer G

    2018-01-01

    Many patients developing a loco-regional recurrence of squamous cell carcinoma of head and neck (SCCHN) have a poor prognosis. Often, recurrences are unresectable, and patients require a second course of radiotherapy or chemoradiation. We present an approach of chemoradiation including mainly 30 Gy of radiotherapy (1.5 Gy twice daily) plus concurrent paclitaxel. To further improve the prognoses of these patients, we increased the radiation dose from 30 to 36 Gy. In four patients with recurrent and previously irradiated SCCHN (60-70 Gy) chemoradiation was carried out using 36 Gy (1.5 Gy twice daily) and concurrent paclitaxel (4-5 times 20-25 mg/m 2 ). One-year loco-regional control rates were 75% inside and 67% outside re-irradiated regions. One-year survival was 50%, and median survival time 11 months. Toxicities were mild (grade 0-2). Re-irradiation with 36 Gy (1.5 Gy twice daily) plus paclitaxel appears feasible and may lead to promising outcomes. This study is preceding a phase I trial. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations.

    Science.gov (United States)

    NeCamp, Timothy; Kilbourne, Amy; Almirall, Daniel

    2017-08-01

    Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

  12. Comparability of patients with ANCA-associated vasculitis enrolled in clinical trials or in observational cohorts

    NARCIS (Netherlands)

    Pagnoux, C.; Carette, S.; Khalidi, N. A.; Walsh, M.; Hiemstra, T. F.; Cuthbertson, D.; Langford, C.; Hoffman, G.; Koening, C. L.; Monach, P. A.; Moreland, L.; Mouthon, L.; Seo, P.; Specks, U.; Ytterbere, S.; Westman, K.; Hoglund, P.; Harper, L.; Flossmann, O.; Luqmani, R.; Savage, C.; Rasmussen, N.; de Groot, K.; Tesar, V.; Jayne, D.; Merkel, P. A.; Guillevin, L.; Stegeman, C. A.

    2015-01-01

    Objective. To analyse the differences between patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) entered into randomised clinical trials (RCTs) and those followed in large observational cohorts. Methods. The main characteristics and outcomes of patients with

  13. Study design considerations in a large COPD trial comparing effects of tiotropium with salmeterol on exacerbations

    NARCIS (Netherlands)

    K-M. Beeh (Kai-Michael); B. Hederer (Bettina); T. Glaab (Thomas); A. Müller (Achim); M.P.M.H. Rutten-van Mölken (Maureen); S. Kesten (Steven); C. Vogelmeier (Claus)

    2009-01-01

    textabstractAbstract Currently available long-acting inhaled bronchodilators (tiotropium, salmeterol, formoterol) have demonstrated beneficial effects on exacerbations in placebo-controlled trials. However, there have been no direct comparisons of these drugs with exacerbations as the primary

  14. Effect of Paclitaxel (Taxol) alone and in combination with radiation on the gastrointestinal mucosa

    International Nuclear Information System (INIS)

    Mason, Kathryn Ann; Milas, Luka; Peters, Lester J.

    1995-01-01

    Purpose: Paclitaxel is a potentially useful drug for augmenting the cytotoxic action of radiotherapy because it has independent cytotoxic activity against certain cancers and blocks cells in the radiosensitive mitotic phase of the cell cycle. However, all rapidly proliferating tissues, both normal and neoplastic, may be affected by this therapeutic strategy. The aim of this study was to define the in vivo response of rapidly dividing cells of the small bowel mucosa to paclitaxel given alone and in combination with radiation. Methods and Materials: Mice were given single IV doses of 10 or 40 mg/kg paclitaxel or four doses of 10 mg/kg paclitaxel at 6, 12, or 24 h intervals. The kinetics of mitotic arrest and apoptosis in jejunal crypts of mice at 1-24 h after treatment were defined histologically. An in vivo stem cell microcolony assay was used to assess the radiosensitizing potential of paclitaxel when radiation was delivered at the peak of mitosis and at 24 h after drug treatment. Results: Paclitaxel blocked jejunal crypt cells in mitosis and induced apoptosis in a dose-dependent manner. Fractionating the paclitaxel dose over 1-4 days did not result in any greater accumulation of mitotically blocked cells than did a single dose. Mitosis peaked 2-4 h after paclitaxel and returned to near normal by 24 h. Apoptosis lagged several hours behind mitosis and peaked about 6 h later than mitosis. Despite these kinetic perturbations, there was little or no enhancement of radiation effect when single doses were delivered 2-4 h after paclitaxel administration. The maximum sensitizer enhancement ratio of 1.07 observed after a single paclitaxel dose of 40 mg/kg is consistent with independent crypt cell killing. Conversely, when radiation was given 24 h after paclitaxel, a significant protective effect of the drug (SER 0.89-0.92), most probably due to a regenerative overshoot induced by paclitaxel, was observed. Conclusion: Stem cells of the jejunal mucosa determining radiation

  15. Pharmacological Modulation of the Mitochondrial Electron Transport Chain in Paclitaxel-Induced Painful Peripheral Neuropathy.

    Science.gov (United States)

    Griffiths, Lisa A; Flatters, Sarah J L

    2015-10-01

    Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive

  16. Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

    Science.gov (United States)

    Le Moulec, Sylvestre; Hadoux, Julien; Gontier, Eric; Chargari, Cyrus; Helissey, Carole; Lamand, Virginie; Tanz, Rachid; Farace, Françoise; Vedrine, Lionel; Bonardel, Gérald; Soria, Jean-Charles; Besse, Benjamin

    2013-12-01

    The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

  17. The Thrombospondin-1 Mimetic ABT-510 Increases the Uptake and Effectiveness of Cisplatin and Paclitaxel in a Mouse Model of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Nicole E. Campbell

    2010-03-01

    Full Text Available Epithelial ovarian cancer (EOC comprises approximately 90% of ovarian cancers and arises from the surface epithelium. Typical treatment of EOC involves cytoreductive surgery combined with chemotherapy. More recent therapies have targeted the tumor vasculature using antiangiogenic compounds such as thrombospondin-1 (TSP-1. TSP-1 mimetic peptides such as ABT-510 have been created and have been in various clinical trials. We have previously shown that ABT-510 reduces abnormal vasculature associated with tumor tissue and increases the presence of mature blood vessels. It has been hypothesized that treatment with antiangiogenic compounds would allow increased delivery of cytotoxic agents and enhance treatment. In this study, we evaluated the potential role of ABT-510 and various chemotherapeutics (cisplatin and paclitaxel on tumor progression, angiogenesis, and the benefits of combinational treatments on tissue uptake and perfusion using an orthotopic syngeneic mouse model of EOC. Animals were treated with ABT-510 (100 mg/kg per day alone or in combination with cisplatin (2 mg/kg per 3 days or paclitaxel (10 mg/kg per 2 days at 60 days after tumor induction. Radiolabeled and fluorescently labeled paclitaxel demonstrated a significant increase in tumor uptake after ABT-510 treatment. Combined treatment with ABT-510 and cisplatin or paclitaxel resulted in a significant increase in tumor cell and tumor endothelial cell apoptosis and a resultant decrease in ovarian tumor size. Combined treatment also regressed secondary lesions and eliminated the presence of abdominal ascites. The results from this study show that through vessel normalization, ABT-510 increases uptake of chemotherapy drugs and can induce regression of advanced ovarian cancer.

  18. A genome-wide RNAi screen identifies novel targets of neratinib sensitivity leading to neratinib and paclitaxel combination drug treatments.

    Science.gov (United States)

    Seyhan, Attila A; Varadarajan, Usha; Choe, Sung; Liu, Yan; McGraw, John; Woods, Matthew; Murray, Stuart; Eckert, Amy; Liu, Wei; Ryan, Terence E

    2011-06-01

    ErbB2 is frequently activated in tumors, and influences a wide array of cellular functions, including proliferation, apoptosis, cell motility and adhesion. HKI-272 (neratinib) is a small molecule pan-kinase inhibitor of the ErbB family of receptor tyrosine kinases, and shows strong antiproliferative activity in ErbB2-overexpressing breast cancer cells. We undertook a genome-wide pooled lentiviral RNAi screen to identify synthetic lethal or enhancer (synthetic modulator screen) genes that interact with neratinib in a human breast cancer cell line (SKBR-3). These genes upon knockdown would modulate cell viability in the presence of subeffective concentrations of neratinib. We discovered a diverse set of genes whose depletion selectively impaired or enhanced the viability of SKBR-3 cells in the presence of neratinib. We observed diverse pathways including EGFR, hypoxia, cAMP, and protein ubiquitination that, when co-treated with RNAi and neratinib, resulted in arrest of cell proliferation. Examining the changes of these genes and their protein products also led to a rationale for clinically relevant drug combination treatments. Treatment of cells with either paclitaxel or cytarabine in combination with neratinib resulted in a strong antiproliferative effect. The identification of novel mediators of cellular response to neratinib and the development of potential drug combination treatments have expanded our understanding of neratinib's mode-of-action for the development of more effective therapeutic regimens. Notably, our findings support a paclitaxel and neratinib phase III clinical trial in breast cancer patients.

  19. A randomized trial comparing didactics, demonstration, and simulation for teaching teamwork to medical residents.

    Science.gov (United States)

    Semler, Matthew W; Keriwala, Raj D; Clune, Jennifer K; Rice, Todd W; Pugh, Meredith E; Wheeler, Arthur P; Miller, Alison N; Banerjee, Arna; Terhune, Kyla; Bastarache, Julie A

    2015-04-01

    Effective teamwork is fundamental to the management of medical emergencies, and yet the best method to teach teamwork skills to trainees remains unknown. In a cohort of incoming internal medicine interns, we tested the hypothesis that expert demonstration of teamwork principles and participation in high-fidelity simulation would each result in objectively assessed teamwork behavior superior to traditional didactics. This was a randomized, controlled, parallel-group trial comparing three teamwork teaching modalities for incoming internal medicine interns. Participants in a single-day orientation at the Vanderbilt University Center for Experiential Learning and Assessment were randomized 1:1:1 to didactic, demonstration-based, or simulation-based instruction and then evaluated in their management of a simulated crisis by five independent, blinded observers using the Teamwork Behavioral Rater score. Clinical performance was assessed using the American Heart Association Advanced Cardiac Life Support algorithm and a novel "Recognize, Respond, Reassess" score. Participants randomized to didactics (n = 18), demonstration (n = 17), and simulation (n = 17) were similar at baseline. The primary outcome of average overall Teamwork Behavioral Rater score for those who received demonstration-based training was similar to simulation participation (4.40 ± 1.15 vs. 4.10 ± 0.95, P = 0.917) and significantly higher than didactic instruction (4.40 ± 1.15 vs. 3.10 ± 0.51, P = 0.045). Clinical performance scores were similar between the three groups and correlated only weakly with teamwork behavior (coefficient of determination [Rs(2)] = 0.267, P teamwork training by expert demonstration resulted in similar teamwork behavior to participation in high-fidelity simulation and was more effective than traditional didactics. Clinical performance was largely independent of teamwork behavior and did not differ between training modalities.

  20. A Randomized Trial Comparing Didactics, Demonstration, and Simulation for Teaching Teamwork to Medical Residents

    Science.gov (United States)

    Keriwala, Raj D.; Clune, Jennifer K.; Rice, Todd W.; Pugh, Meredith E.; Wheeler, Arthur P.; Miller, Alison N.; Banerjee, Arna; Terhune, Kyla; Bastarache, Julie A.

    2015-01-01

    Rationale: Effective teamwork is fundamental to the management of medical emergencies, and yet the best method to teach teamwork skills to trainees remains unknown. Objectives: In a cohort of incoming internal medicine interns, we tested the hypothesis that expert demonstration of teamwork principles and participation in high-fidelity simulation would each result in objectively assessed teamwork behavior superior to traditional didactics. Methods: This was a randomized, controlled, parallel-group trial comparing three teamwork teaching modalities for incoming internal medicine interns. Participants in a single-day orientation at the Vanderbilt University Center for Experiential Learning and Assessment were randomized 1:1:1 to didactic, demonstration-based, or simulation-based instruction and then evaluated in their management of a simulated crisis by five independent, blinded observers using the Teamwork Behavioral Rater score. Clinical performance was assessed using the American Heart Association Advanced Cardiac Life Support algorithm and a novel “Recognize, Respond, Reassess” score. Measurements and Main Results: Participants randomized to didactics (n = 18), demonstration (n = 17), and simulation (n = 17) were similar at baseline. The primary outcome of average overall Teamwork Behavioral Rater score for those who received demonstration-based training was similar to simulation participation (4.40 ± 1.15 vs. 4.10 ± 0.95, P = 0.917) and significantly higher than didactic instruction (4.40 ± 1.15 vs. 3.10 ± 0.51, P = 0.045). Clinical performance scores were similar between the three groups and correlated only weakly with teamwork behavior (coefficient of determination [Rs2] = 0.267, P didactics. Clinical performance was largely independent of teamwork behavior and did not differ between training modalities. PMID:25730661

  1. Contura Multi-Lumen Balloon Breast Brachytherapy Catheter: Comparative Dosimetric Findings of a Phase 4 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Arthur, Douglas W., E-mail: darthur@mcvh-vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Vicini, Frank A. [Michigan Healthcare Professionals/21st Century Oncology, Farmington Hills, Michigan (United States); Todor, Dorin A. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Julian, Thomas B. [Allegheny General Hospital, Temple University School of Medicine, Pittsburgh, Pennsylvania (United States); Cuttino, Laurie W.; Mukhopadhyay, Nitai D. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States)

    2013-06-01

    Purpose: Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Methods and Materials: Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥95% of the prescribed dose (PD) covering ≥95% of the target volume (TV); maximum skin dose ≤125% of the PD; maximum rib dose ≤145% of the PD; and V150 ≤50 cc and V200 ≤10 cc. Results: Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Conclusions: Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals.

  2. Contura Multi-Lumen Balloon breast brachytherapy catheter: comparative dosimetric findings of a phase 4 trial.

    Science.gov (United States)

    Arthur, Douglas W; Vicini, Frank A; Todor, Dorin A; Julian, Thomas B; Cuttino, Laurie W; Mukhopadhyay, Nitai D

    2013-06-01

    Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥ 95% of the prescribed dose (PD) covering ≥ 95% of the target volume (TV); maximum skin dose ≤ 125% of the PD; maximum rib dose ≤ 145% of the PD; and V150 ≤50 cc and V200 ≤ 10 cc. Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P ≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals. Copyright © 2013 Elsevier Inc. All rights

  3. Cost utility analysis of co-prescribed heroin compared with methadone maintenance treatment in heroin addicts in two randomised trials

    NARCIS (Netherlands)

    Dijkgraaf, Marcel G. W.; van der Zanden, Bart P.; de Borgie, Corianne A. J. M.; Blanken, Peter; van Ree, Jan M.; van den Brink, Wim

    2005-01-01

    Objective To determine the cost utility of medical co-prescription of heroin compared with methadone maintenance treatment for chronic, treatment resistant heroin addicts. Design Cost utility analysis of two pooled open label randomised controlled trials. Setting Methadone maintenance programmes in

  4. Conservative treatment of a mandibular condyle fracture: comparing intermaxillary fixation with screws or arch bar. A randomised clinical trial

    NARCIS (Netherlands)

    van den Bergh, B.; Blankestijn, J.; van der Ploeg, T.; Tuinzing, D.B.; Forouzanfar, T.

    2015-01-01

    Introduction A mandibular condyle fracture can be treated conservatively by intermaxillary fixation (IMF) or by open reposition and internal fixation (ORIF). Many IMF-modalities can be chosen, including IMF-screws (IMFS). This prospective multi-centre randomised clinical trial compared the use of

  5. Conservative treatment of a mandibular condyle fracture: Comparing intermaxillary fixation with screws or arch bar. A randomised clinical trial

    NARCIS (Netherlands)

    van den Bergh, B.; Blankestijn, J.; van der Ploeg, T.; Tuinzing, D.B.; Forouzanfar, T.

    2015-01-01

    Introduction A mandibular condyle fracture can be treated conservatively by intermaxillary fixation (IMF) or by open reposition and internal fixation (ORIF). Many IMF-modalities can be chosen, including IMF-screws (IMFS). This prospective multi-centre randomised clinical trial compared the use of

  6. A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes

    DEFF Research Database (Denmark)

    Hod, Moshe; Mathiesen, Elisabeth R; Jovanovič, Lois

    2014-01-01

    OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both with insulin aspart, in pregnant women with type 1 diabetes. The perinatal and obstetric pregnancy outcomes are presented. METHODS: Subjects w...

  7. Examination of Individual Differences in Outcomes from a Randomized Controlled Clinical Trial Comparing Formal and Informal Individual Auditory Training Programs

    Science.gov (United States)

    Smith, Sherri L.; Saunders, Gabrielle H.; Chisolm, Theresa H.; Frederick, Melissa; Bailey, Beth A.

    2016-01-01

    Purpose: The purpose of this study was to determine if patient characteristics or clinical variables could predict who benefits from individual auditory training. Method: A retrospective series of analyses were performed using a data set from a large, multisite, randomized controlled clinical trial that compared the treatment effects of at-home…

  8. A multicenter, randomized trial comparing synthetic surfactant with modified bovine surfactant extract in the treatment of neonatal respiratory distress syndrome

    NARCIS (Netherlands)

    Adams, E; Vollman, J; Giebner, D; Maurer, M; Dreyer, G; Bailey, L; Anderson, M; Mefford, L; Beaumont, E; Sutton, D; Puppala, B; Mangurten, HH; Secrest, J; Lewis, WJ; Carteaux, P; Bednarek, F; Welsberger, S; Gosselin, R; Pantoja, AF; Belenky, A; Campbell, P; Patole, S; Duenas, M; Kelly, M; Alejo, W; Lewallen, P; DeanLieber, S; Hanft, M; Ferlauto, J; Newell, RW; Bagwell, J; Levine, D; Lipp, RW; Harkavy, K; Vasa, R; Birenbaum, H; Broderick, KA; Santos, AQ; Long, BA; Gulrajani, M; Stern, M; Hopgood, G; Hegyi, T; Alba, J; Christmas, L; McQueen, M; Nichols, N; Brown, M; Quissell, BJ; Rusk, C; Marks, K; Gifford, K; Hoehn, G; Pathak, A; Marino, B; Hunt, P; Fox, [No Value; Sharpstein, C; Feldman, B; Johnson, N; Beecham, J; Balcom, R; Helmuth, W; Boylan, D; Frakes, C; Magoon, M; Reese, K; Schwersenski, J; Schutzman, D; Soll, R; Horbar, JD; Leahy, K; Troyer, W; Juzwicki, C; Anderson, P; Dworsky, M; Reynolds, L; Urrutia, J; Gupta, U; Adray, C

    Objective. To compare the efficacy of a synthetic surfactant (Exosurf Neonatal, Burroughs-Wellcome Co) and a modified bovine surfactant extract (Survanta, Ross Laboratories) in the treatment of neonatal respiratory distress syndrome (RDS). Design. Multicenter, randomized trial. Setting. Thirty-eight

  9. Schedule-dependent interaction of paclitaxel (taxol[reg]) and irradiation in vitro

    International Nuclear Information System (INIS)

    Plasswilm, Ludwig; Cordes, Nils

    1996-01-01

    Purpose/Objective: The optimal dose and schedule of paclitaxel in combination with irradiation has not been determined yet. The aim of our study was first to compare the in vitro cytotoxicity and enhancement of radiation sensitization as a function of single dose versus fractionated paclitaxel administration. Secondly the cytotoxicity of the solvent cremophor/ethanol alone was evaluated and compared to the effect of Taxol[reg]. Materials and Methods: A fibroblast cell line (B14) in exponential growth phase with a doubling time of approximately 12 hours was used. Untreated cells and cells treated with phosphate buffered saline (PBS) were plated and used as control. Single dose and fractionated irradiation of 0 to 20 Gy (2.2 Gy/min) was delivered to the cells. Cytotoxicity of Taxol[reg] was examined at concentrations varied from 2 to 50 nmol compared to aliquots of cremophor/ethanol. Single dose (1x10 nmol) versus fractionated (2 nmol/day, day 1 to day 5) administration of Taxol[reg] was investigated. The combination of Taxol[reg] plus irradiation as single dose and fractionated administration was accomplished with 10 nmol Taxol[reg] on day 1 plus 10 Gy irradiation on day 1 (single dose administration) versus Taxol[reg], 2 nmol/day, day 1 to day 5, plus irradiation, 2 Gy/day, day 1 to day 5 (fractionated administration). Taxol[reg] administration was always performed for a 3 hour period with a 1-hour and 9-hour interval between Taxol[reg] administration and irradiation. All experiments were repeated in the same schedule with single dose and fractional administration of cremophor/ethanol. The clonogenic assay was applied to determine cell survival. Flow cytometric measurements were performed to study cell cycle DNA distribution. Results: Untreated controls and PBS treated cells (single dose and fractionated schedule) demonstrate an average plating efficiency of 93%. Single dose Taxol[reg] (1x10 nmol) administration show an average clonogenic survival of 88% (cremophor

  10. Methodological reporting of randomized controlled trials in major hepato-gastroenterology journals in 2008 and 1998: a comparative study

    Science.gov (United States)

    2011-01-01

    Background It was still unclear whether the methodological reporting quality of randomized controlled trials (RCTs) in major hepato-gastroenterology journals improved after the Consolidated Standards of Reporting Trials (CONSORT) Statement was revised in 2001. Methods RCTs in five major hepato-gastroenterology journals published in 1998 or 2008 were retrieved from MEDLINE using a high sensitivity search method and their reporting quality of methodological details were evaluated based on the CONSORT Statement and Cochrane Handbook for Systematic Reviews of interventions. Changes of the methodological reporting quality between 2008 and 1998 were calculated by risk ratios with 95% confidence intervals. Results A total of 107 RCTs published in 2008 and 99 RCTs published in 1998 were found. Compared to those in 1998, the proportion of RCTs that reported sequence generation (RR, 5.70; 95%CI 3.11-10.42), allocation concealment (RR, 4.08; 95%CI 2.25-7.39), sample size calculation (RR, 3.83; 95%CI 2.10-6.98), incomplete outecome data addressed (RR, 1.81; 95%CI, 1.03-3.17), intention-to-treat analyses (RR, 3.04; 95%CI 1.72-5.39) increased in 2008. Blinding and intent-to-treat analysis were reported better in multi-center trials than in single-center trials. The reporting of allocation concealment and blinding were better in industry-sponsored trials than in public-funded trials. Compared with historical studies, the methodological reporting quality improved with time. Conclusion Although the reporting of several important methodological aspects improved in 2008 compared with those published in 1998, which may indicate the researchers had increased awareness of and compliance with the revised CONSORT statement, some items were still reported badly. There is much room for future improvement. PMID:21801429

  11. Smoking-Cessation Interventions for Urban Hospital Patients: A Randomized Comparative Effectiveness Trial.

    Science.gov (United States)

    Sherman, Scott E; Link, Alissa R; Rogers, Erin S; Krebs, Paul; Ladapo, Joseph A; Shelley, Donna R; Fang, Yixin; Wang, Binhuan; Grossman, Ellie

    2016-10-01

    Hospitalization is a unique opportunity for smoking cessation, but prior interventions have measured efficacy with narrowly defined populations. The objective of this study was to enroll smokers admitted to two "safety net" hospitals and compare the effectiveness of two post-discharge cessation interventions. A randomized comparative effectiveness trial was conducted. At two New York City public hospitals, every hospitalized patient identified as a smoker (based on admission records) was approached. Inclusion criteria were: smoked cigarettes in the past 30 days; spoke English, Spanish, or Mandarin; had a U.S. phone number; not discharged to an institution where follow-up or smoking was limited; and not pregnant/breastfeeding. Of 18,797 patients identified as current smokers between July 2011 and April 2014, a total of 3,047 (16%) were discharged before being approached, 3,273 (17%) were not current smokers, 4,026 (21%) had no U.S. phone number, 2,831 (15%) were ineligible for other reasons, and 3,983 (21%) refused participation. In total, 1,618 (9%) participants enrolled in the study. During follow-up, 69% of participants were reached at 2 months and 68% at 6 months. At discharge, participants were randomized to multisession telephone counseling from study staff (n=804) or referral to the state quitline for proactive outreach and counseling (n=814). Self-reported abstinence at 6 months was measured. Analyses were conducted in late 2015. One quarter of participants were homeless or in unstable housing, 60% had a history of substance abuse, 43% reported current hazardous drinking, and half had a psychiatric diagnosis other than substance abuse. At follow-up, the rate of abstinence (30-day point prevalence) was higher in the intensive counseling arm than the quitline arm at 2 months (29.0% vs 20.7%; relative risk=1.40; 95% CI=1.13, 1.73) and 6 months (37.4% vs 31.5%; relative risk=1.19; 95% CI=1.01, 1.40). Intensive counseling was more effective than referral to the

  12. Impact of different nasal masks on CPAP therapy for obstructive sleep apnea: a randomized comparative trial.

    Science.gov (United States)

    Neuzeret, Pierre-Charles; Morin, Laurent

    2017-11-01

    Patient interface is important for the success of continuous positive airway pressure (CPAP), but few trials have examined the influence of mask choice on CPAP adherence. To compare the impact of different nasal masks on CPAP in patients with newly-diagnosed obstructive sleep apnea (OSA). OSA patients were randomized in a 2:3 ratio to receive CPAP via different first-line nasal masks: ResMed Mirage FX® (MFX) or control mask (Fisher & Paykel Zest ® , HC407 ® or Philips EasyLife ® ). Mask acceptance, CPAP compliance and Home Care Provider (HCP) interventions were compared between groups after 3 months of CPAP therapy using modified intent-to-treat (mITT; after exclusion of patients with mouth leaks during CPAP initiation) and on-treatment (OT; CPAP adherent) analyses. Of 285 randomized patients, 90 requiring a full-face mask were excluded, leaving 195 and 151 in the mITT and OT analyses, respectively. Mask acceptance rate was higher in the MFX versus control group (mITT: 79% vs 68%, P = 0.067; OT: 90% vs 76%, P = 0.022). CPAP compliance was higher (5.9 ± 1.8 vs 5.1 ± 1.6 h/night, P = 0.011) and nasal mask issue-related HCP visits lower (3% vs 17%, P = 0.006) in the MFX group. Nasal mask failures due to mask discomfort (5% vs 1%) or unintentional leakage (5% vs 0%) were higher in control vs MFX group. Mask acceptance was significantly associated with fewer mask leaks (P = 0.002) and higher pressure therapy (P = 0.042). This study highlights differences between nasal masks for CPAP delivery and shows that initial mask selection can influence adherence and healthcare utilization during CPAP. © 2016 ResMed Germany Inc. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.

  13. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

    Science.gov (United States)

    Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

    2017-09-01

    Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

  14. Protocol for a multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapy-led care for femoroacetabular impingement (FAI): the Australian FASHIoN trial.

    Science.gov (United States)

    Murphy, Nicholas J; Eyles, Jillian; Bennell, Kim L; Bohensky, Megan; Burns, Alexander; Callaghan, Fraser M; Dickenson, Edward; Fary, Camdon; Grieve, Stuart M; Griffin, Damian R; Hall, Michelle; Hobson, Rachel; Kim, Young Jo; Linklater, James M; Lloyd, David G; Molnar, Robert; O'Connell, Rachel L; O'Donnell, John; O'Sullivan, Michael; Randhawa, Sunny; Reichenbach, Stephan; Saxby, David J; Singh, Parminder; Spiers, Libby; Tran, Phong; Wrigley, Tim V; Hunter, David J

    2017-09-26

    Femoroacetabular impingement syndrome (FAI), a hip disorder affecting active young adults, is believed to be a leading cause of hip osteoarthritis (OA). Current management approaches for FAI include arthroscopic hip surgery and physiotherapy-led non-surgical care; however, there is a paucity of clinical trial evidence comparing these approaches. In particular, it is unknown whether these management approaches modify the future risk of developing hip OA. The primary objective of this randomised controlled trial is to determine if participants with FAI who undergo hip arthroscopy have greater improvements in hip cartilage health, as demonstrated by changes in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to those who undergo physiotherapy-led non-surgical management. This is a pragmatic, multi-centre, two-arm superiority randomised controlled trial comparing hip arthroscopy to physiotherapy-led management for FAI. A total of 140 participants with FAI will be recruited from the clinics of participating orthopaedic surgeons, and randomly allocated to receive either surgery or physiotherapy-led non-surgical care. The surgical intervention involves arthroscopic FAI surgery from one of eight orthopaedic surgeons specialising in this field, located in three different Australian cities. The physiotherapy-led non-surgical management is an individualised physiotherapy program, named Personalised Hip Therapy (PHT), developed by a panel to represent the best non-operative care for FAI. It entails at least six individual physiotherapy sessions over 12 weeks, and up to ten sessions over six months, provided by experienced musculoskeletal physiotherapists trained to deliver the PHT program. The primary outcome measure is the change in dGEMRIC score of a ROI containing both acetabular and femoral head cartilages at the chondrolabral transitional zone of the mid-sagittal plane between baseline and

  15. Biodistribution imaging of a paclitaxel-hyaluronan bioconjugate

    Energy Technology Data Exchange (ETDEWEB)

    Banzato, Alessandra; Rondina, Maria [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Melendez-Alafort, Laura; Zangoni, Elena; Nadali, Anna [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Renier, Davide [Fidia Farmaceutici, Abano Terme (Italy); Moschini, Giuliano [Department of Physics, University of Padua, Padova (Italy); Mazzi, Ulderico [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Zanovello, Paola [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy); Rosato, Antonio [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy)], E-mail: antonio.rosato@unipd.it

    2009-07-15

    Introduction: Gamma-ray detectors represent sensitive and noninvasive instruments to evaluate in vivo the metabolic trapping of radiopharmaceuticals. This study aimed to assess the imaging biodistribution of a [{sup 99m}Tc]-radiolabelled new prototype bioconjugate composed of paclitaxel linked to hyaluronan (ONCOFID-P). Methods: A small gamma camera providing high-resolution images was employed. Imaging of biodistribution following intravenous, intraperitoneal, intravesical and oral administration was carried out for a 2-h period in anesthetized mice receiving [{sup 99m}Tc]ONCOFID-P. At the end of the observation time, radioactivity in organs was directly measured. As a control, groups of mice were treated with free [{sup 3}H]paclitaxel given according to the same administration routes, and organ biodistribution of the drug was assessed after 2 h. Results: Intravenous inoculation of [{sup 99m}Tc]ONCOFID-P was followed by a rapid and strong liver uptake. In fact, almost 80% of the imaging signal was detected in this organ 10 min after injection and such value remained constant thereafter, thus indicating that the bioconjugate given through the intravenous route could be well suited to targeting primary or metastatic liver neoplasias. Imaging of the bladder, abdomen and gastrointestinal tract after local administration disclosed that the radiolabelled compound remained confined to the cavities, suggesting a potential regional application for transitional bladder cell carcinomas, ovarian cancers and gastric tumors, respectively. Free [{sup 3}H]paclitaxel biodistribution profoundly differed from that of [{sup 99m}Tc]ONCOFID-P. Conclusions: Conjugation of drugs with polymers results in new chemical entities characterized by a modified biodistribution pattern. Therefore, preclinical studies based on imaging analysis of such new compounds can suggest novel therapeutic applications.

  16. Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters

    International Nuclear Information System (INIS)

    Němcová-Fürstová, Vlasta; Kopperová, Dana; Balušíková, Kamila; Ehrlichová, Marie; Brynychová, Veronika; Václavíková, Radka; Daniel, Petr; Souček, Pavel; Kovář, Jan

    2016-01-01

    Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100 nM and 300 nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype. Interestingly, resistance in both paclitaxel-resistant sublines is circumvented by the second-generation taxane SB-T-1216. Moreover, we demonstrated that it was not possible to establish sublines of SK-BR-3 and MCF-7 cells resistant to this taxane. It means that at least the tested breast cancer cells are unable to develop resistance to some taxanes. Employing mRNA expression profiling of all known human ABC transporters and subsequent Western blot analysis of the expression of selected transporters, we demonstrated that only the ABCB1/PgP and ABCC3/MRP3 proteins were up-regulated in both paclitaxel-resistant sublines. We found up-regulation of ABCG2/BCRP and ABCC4 proteins only in paclitaxel-resistant SK-BR-3 cells. In paclitaxel-resistant MCF-7 cells, ABCB4/MDR3 and ABCC2/MRP2 proteins were up-regulated. Silencing of ABCB1 expression using specific siRNA increased significantly, but did not completely restore full sensitivity to both paclitaxel and doxorubicin. Thus we showed a key, but not exclusive, role for ABCB1 in mechanisms of paclitaxel resistance. It suggests the involvement of multiple mechanisms in paclitaxel resistance in tested breast cancer cells. - Highlights: • Expression of all ABC transporters in paclitaxel-resistant sublines of SK-BR-3 and MCF-7 cells was analyzed. • SK-BR-3 and MCF-7 cells are unable to develop resistance to some taxanes. • Some taxanes are able to overcome developed resistance to

  17. Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters

    Energy Technology Data Exchange (ETDEWEB)

    Němcová-Fürstová, Vlasta, E-mail: vlasta.furstova@lf3.cuni.cz [Division of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Kopperová, Dana; Balušíková, Kamila [Division of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Ehrlichová, Marie; Brynychová, Veronika; Václavíková, Radka [Toxicogenomics Unit, National Institute of Public Health, Prague (Czech Republic); Daniel, Petr [Division of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Souček, Pavel [Toxicogenomics Unit, National Institute of Public Health, Prague (Czech Republic); Kovář, Jan [Division of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic)

    2016-11-01

    Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100 nM and 300 nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype. Interestingly, resistance in both paclitaxel-resistant sublines is circumvented by the second-generation taxane SB-T-1216. Moreover, we demonstrated that it was not possible to establish sublines of SK-BR-3 and MCF-7 cells resistant to this taxane. It means that at least the tested breast cancer cells are unable to develop resistance to some taxanes. Employing mRNA expression profiling of all known human ABC transporters and subsequent Western blot analysis of the expression of selected transporters, we demonstrated that only the ABCB1/PgP and ABCC3/MRP3 proteins were up-regulated in both paclitaxel-resistant sublines. We found up-regulation of ABCG2/BCRP and ABCC4 proteins only in paclitaxel-resistant SK-BR-3 cells. In paclitaxel-resistant MCF-7 cells, ABCB4/MDR3 and ABCC2/MRP2 proteins were up-regulated. Silencing of ABCB1 expression using specific siRNA increased significantly, but did not completely restore full sensitivity to both paclitaxel and doxorubicin. Thus we showed a key, but not exclusive, role for ABCB1 in mechanisms of paclitaxel resistance. It suggests the involvement of multiple mechanisms in paclitaxel resistance in tested breast cancer cells. - Highlights: • Expression of all ABC transporters in paclitaxel-resistant sublines of SK-BR-3 and MCF-7 cells was analyzed. • SK-BR-3 and MCF-7 cells are unable to develop resistance to some taxanes. • Some taxanes are able to overcome developed resistance to

  18. Cost-effectiveness analysis of paclitaxel + carboplatin vs. alternative combinations in the treatment of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2006-06-01

    Full Text Available Non-small cell lung cancer (NSCLC is the most common type of lung cancer and its medical and economical burden represents a serious matter in Europe and Usa, due to its high mortality rates and drug costs. Lung cancer is responsible for about 30% of cancer death in men and women; in Europe only about 8 per cent of people with lung cancer survive for 5 years. At present combination chemotherapy based on cisplatin or carboplatin associated with paclitaxel, vinorelbine or gemcitabine is the state of the art for the treatment in patients with stage IIIb or IV NSCLC. Aim of this study was to compare the cost-effectiveness of paclitaxel/carboplatin (PCb, gemcitabine/cisplatin (GC and vinorelbine/cisplatin (VC in the perspective of the Italian National Health Service. Therefore we perfomed a semi-Markov decision model mainly based on clinical results from the Italian Lung Cancer Project. The model included differential direct medical costs registered for two years from starting chemotherapy, using tariffs valid for 2005. Benefits was measured by years of life saved (YOLs. The model also allowed to estimate only costs accrued over the period of time, performing a cost-minimisation analysis. According to cost-effectiveness analysis, VC is dominated because it’s more costly and less effective than GC. On the contrary, combination chemotherapy with GC is more inexpensive but less effective than paclitaxel/carboplatin (PCb: in this case we compared the incremental cost-effectiveness ratio (ICER with a maximum acceptable willingness-to-pay (WTP value. In the base scenario the ICER of PCb over GC treatment is 52,326 euro/ YOLs, which is definitely lower than the maximum acceptable WTP value. Sensitivity analyses confirmed the robustness of the results from cost-effectiveness analysis in the base scenario.

  19. A mucoadhesive in situ gel delivery system for paclitaxel

    OpenAIRE

    Jauhari, Saurabh; Dash, Alekha K.

    2006-01-01

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at d...

  20. Employment and paid work among participants in a randomized controlled trial comparing diacetylmorphine and hydromorphone.

    Science.gov (United States)

    Nikoo, Mohammadali; Vogel, Marc; Choi, Fiona; Song, Michael J; Burghardt, Jensen; Zafari, Zafar; Tabi, Katarina; Frank, Anastasia; Barbic, Skye; Schütz, Christian; Jang, Kerry; Krausz, Michael

    2018-04-12

    Employment is one of the less studied but a significant outcome of medication-assisted treatment. Thus, we aimed to explore employment outcomes of medication-assisted treatment with hydromorphone (HDM) or diacetylmorphine (DAM). The secondary aim was to estimate characteristics of this population as well as treatment-related factors associated with these outcomes. This was a secondary analysis of a randomized, double blind controlled trial. A total of 102 and 100 participants were randomized to receive injectable DAM or HDM for 6 months respectively. In stage 2, 144 participants were randomized again to receive either oral or injectable forms of the medication they received for another 6 months. Participants were interviewed at 5 timepoints: before and 3, 6, 9 and 12 months after treatment assignment. Generalized estimating equations (GEE) with a logit link was fitted to determine factors related to paid work in the past 30 days. Mean age of participants was 44.3 (SD = 9.6) and 59 (29.2%) participants were men. At each timepoint, 6-8 (3.6%-4.1%) participants reported employment in the past 30 days and 40 to 52 (19.7%-26.7%) reported minimum 1 day of paid work. University or college education [OR = 2.12: 95% CI = (1.25, 3.62), P = 0.01] was significantly associated with paid work after adjustment for age, gender, treatment arms, timepoints, days receiving study treatment, physical health, psychological health and crack cocaine use in the past 30 days. The rate of employment was lower among participants of this study compared to similar studies on heroin-assisted treatment. Higher education was associated with increased odds of paid work. A large gap exists between employment rate and the proportion of participants who reported paid work. Supported employment and occupational therapy could optimize the employment outcomes of this population. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. A Randomized Clinical Trial Comparing Methotrexate and Mycophenolate Mofetil for Non-Infectious Uveitis

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne TA; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-01-01

    Objective To compare the relative effectiveness of methotrexate and mycophenolate mofetil for non-infectious intermediate uveitis, posterior uveitis, or panuveitis. Design Multicenter, block-randomized, observer-masked clinical trial Participants Eighty patients with non-infectious intermediate, posterior or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Intervention Patients were randomized to receive 25mg weekly oral methotrexate or 1g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Main Outcome Measures Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤ 10 mg of prednisone and ≤ 2 drops of prednisolone acetate 1% a day and (3) no declaration of treatment failure due to intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Results Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (p=0.09). Treatment failure due to adverse events or tolerability was not significantly different by treatment arm (p=0.99). There were no statistically significant differences between treatment groups in time to corticosteroid-sparing control of inflammation (p=0.44), change in best spectacle-corrected visual acuity (p=0.68), and resolution of macular

  2. A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne T A; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-10-01

    To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Multicenter, block-randomized, observer-masked clinical trial. Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). There was no statistically significant difference in corticosteroid-sparing control of

  3. Randomized clinical trial comparing control of maxillary anchorage with 2 retraction techniques.

    Science.gov (United States)

    Xu, Tian-Min; Zhang, Xiaoyun; Oh, Hee Soo; Boyd, Robert L; Korn, Edward L; Baumrind, Sheldon

    2010-11-01

    The objective of this pilot randomized clinical trial was to investigate the relative effectiveness of anchorage conservation of en-masse and 2-step retraction techniques during maximum anchorage treatment in patients with Angle Class I and Class II malocclusions. Sixty-four growing subjects (25 boys, 39 girls; 10.2-15.9 years old) who required maximum anchorage were randomized to 2 treatment techniques: en-masse retraction (n = 32) and 2-step retraction (n = 32); the groups were stratified by sex and starting age. Each patient was treated by a full-time clinic instructor experienced in the use of both retraction techniques at the orthodontic clinic of Peking University School of Stomatology in China. All patients used headgear, and most had transpalatal appliances. Lateral cephalograms taken before treatment and at the end of treatment were used to evaluate treatment-associated changes. Differences in maxillary molar mesial displacement and maxillary incisor retraction were measured with the before and after treatment tracings superimposed on the anatomic best fit of the palatal structures. Differences in mesial displacement of the maxillary first molar were compared between the 2 treatment techniques, between sexes, and between different starting-age groups. Average mesial displacement of the maxillary first molar was slightly less in the en-masse group than in the 2-step group (mean, -0.36 mm; 95% CI, -1.42 to 0.71 mm). The average mesial displacement of the maxillary first molar for both treatment groups pooled (n = 63, because 1 patient was lost to follow-up) was 4.3 ± 2.1 mm (mean ± standard deviation). Boys had significantly more mesial displacement than girls (mean difference, 1.3 mm; P <0.03). Younger adolescents had significantly more mesial displacement than older adolescents (mean difference, 1.3 mm; P <0.02). Average mesial displacement of the maxillary first molar with 2-step retraction was slightly greater than that for en-masse retraction, but the

  4. Comparative effectiveness of childhood obesity interventions in pediatric primary care: a cluster-randomized clinical trial.

    Science.gov (United States)

    Taveras, Elsie M; Marshall, Richard; Kleinman, Ken P; Gillman, Matthew W; Hacker, Karen; Horan, Christine M; Smith, Renata L; Price, Sarah; Sharifi, Mona; Rifas-Shiman, Sheryl L; Simon, Steven R

    2015-06-01

    Evidence of effective treatment of childhood obesity in primary care settings is limited. To examine the extent to which computerized clinical decision support (CDS) delivered to pediatric clinicians at the point of care of obese children, with or without individualized family coaching, improved body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and quality of care. We conducted a cluster-randomized, 3-arm clinical trial. We enrolled 549 children aged 6 to 12 years with a BMI at the 95% percentile or higher from 14 primary care practices in Massachusetts from October 1, 2011, through June 30, 2012. Patients were followed up for 1 year (last follow-up, August 30, 2013). In intent-to-treat analyses, we used linear mixed-effects models to account for clustering by practice and within each person. In 5 practices randomized to CDS, pediatric clinicians received decision support on obesity management, and patients and their families received an intervention for self-guided behavior change. In 5 practices randomized to CDS + coaching, decision support was augmented by individualized family coaching. The remaining 4 practices were randomized to usual care. Smaller age-associated change in BMI and the Healthcare Effectiveness Data and Information Set (HEDIS) performance measures for obesity during the 1-year follow-up. At baseline, mean (SD) patient age and BMI were 9.8 (1.9) years and 25.8 (4.3), respectively. At 1 year, we obtained BMI from 518 children (94.4%) and HEDIS measures from 491 visits (89.4%). The 3 randomization arms had different effects on BMI over time (P = .04). Compared with the usual care arm, BMI increased less in children in the CDS arm during 1 year (-0.51 [95% CI, -0.91 to -0.11]). The CDS + coaching arm had a smaller magnitude of effect (-0.34 [95% CI, -0.75 to 0.07]). We found substantially greater achievement of childhood obesity HEDIS measures in the CDS arm (adjusted odds ratio, 2.28 [95% CI, 1

  5. Comparative prospective randomized trial: laparoscopic versus open common bile duct exploration

    Directory of Open Access Journals (Sweden)

    Vladimir Grubnik

    2011-06-01

    Full Text Available Introduction: Single-stage laparoscopic procedures for common bile duct (CBD stones are an alternative treatmentoption to two-stage endo-laparoscopic treatment and to open choledocholithotomy. Several reports have demonstratedthe feasibility, safety, efficiency and cost-effectiveness of laparoscopic techniques.Aim: To analyse the safety and benefits of laparoscopic compared to open common bile duct (CBD exploration.Material and methods: The prospective randomized trial included a total of 256 patients with CBD stones operated from2005 to 2009 in a single centre. The male/female ratio was 82/174, with a median age 62.3 ±5.8 years (range 27 to 87years. There were two groups of patients. Group I: laparoscopic CBD exploration (138 patients. Group II: open CBD exploration(118 patients. Patient comorbidity was assessed by means of the American Society of Anesthesiologists (ASA classification;ASA II – 109 patients, ASA III – 59 patients. Bile duct stones were visualized preoperatively by means of US examinationin 129 patients, by means of ERCP in 26 patients, and by magnetic resonance cholangiopancreatography (MRCPin 72 patients. Preoperative evaluation was done through medical history, biochemical tests and ultrasonography.Results: The mean duration of laparoscopic procedures was 82 min (range 40-160 min. The mean duration of openprocedures was 90 min (range 60-150 min. Mean blood loss was much lower in the laparoscopic group than in theopen group (20 ±2 v.s 285 ±27, p < 0.01. Postoperative complications were observed in 7 patients of the laparoscopicgroup and in 15 patients in the open group (p < 0.01. Laparoscopic common bile duct exploration was performedthrough a trans-cystic approach in 76 patients and via choledochotomy in 62 patients. The transcystic approach wassuccessful in 76 patients (74.5%. External drainage was used in 25 (32.8% patients with the transcystic approach.Conclusions: Laparoscopic CBD exploration can be performed with

  6. Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer.

    Science.gov (United States)

    Clark, C H; Miles, E A; Urbano, M T Guerrero; Bhide, S A; Bidmead, A M; Harrington, K J; Nutting, C M

    2009-07-01

    The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.

  7. Expanding the Evidence Base: Comparing Randomized Controlled Trials and Observational Studies of Statins

    NARCIS (Netherlands)

    Atar, Dan; Ong, Seleen; Lansberg, Peter J.

    2015-01-01

    It is widely accepted that randomized controlled trials (RCTs) are the gold standard for demonstrating the efficacy of a given therapy (results under ideal conditions). Observational studies, on the other hand, can complement this by demonstrating effectiveness (results under real-world conditions).

  8. Explaining Feast or Famine in Randomized Field Trials: Medical Science and Criminology Compared.

    Science.gov (United States)

    Shepherd, Jonathan P.

    2003-01-01

    Discusses the contrast between the frequency of randomized clinical trials in the health sciences and the relative famine of such studies in criminology. Attributes this difference to the contexts in which research is done and the difference in the status of situational research in the two disciplines. (SLD)

  9. The Tilburg double blind randomised controlled trial comparing inguinal hernia repair according to Lichtenstein and the transinguinal preperitoneal technique

    Directory of Open Access Journals (Sweden)

    Gerritsen Pieter G

    2009-09-01

    Full Text Available Abstract Background Anterior open treatment of the inguinal hernia with a tension free mesh has reduced the incidence of recurrence and direct postoperative pain. The Lichtenstein procedure rules nowadays as reference technique for hernia treatment. Not recurrences but chronic pain is the main postoperative complication in inguinal hernia repair after Lichtenstein's technique. Preliminary experiences with a soft mesh placed in the preperitoneal space showed good results and less chronic pain. Methods The TULIP is a double-blind randomised controlled trial in which 300 patients will be randomly allocated to anterior inguinal hernia repair according to Lichtenstein or the transinguinal preperitoneal technique with soft mesh. All unilateral primary inguinal hernia patients eligible for operation who meet inclusion criteria will be invited to participate in this trial. The primary endpoint will be direct postoperative- and chronic pain. Secondary endpoints are operation time, postoperative complications, hospital stay, costs, return to daily activities (e.g. work and recurrence. Both groups will be evaluated. Success rate of hernia repair and complications will be measured as safeguard for quality. To demonstrate that inguinal hernia repair according to the transinguinal preperitoneal (TIPP technique reduces postoperative pain to Discussion The TULIP trial is aimed to show a reduction in postoperative chronic pain after anterior hernia repair according to the transinguinal preperitoneal (TIPP technique, compared to Lichtenstein. In our hypothesis the TIPP technique reduces chronic pain compared to Lichtenstein. Trial registration ISRCTN 93798494

  10. Systematic review and meta-analysis of published, randomized, controlled trials comparing suture anastomosis to stapled anastomosis for ileostomy closure.

    Science.gov (United States)

    Sajid, M S; Craciunas, L; Baig, M K; Sains, P

    2013-12-01

    The objective of this article is to systematically analyze the randomized, controlled trials comparing the effectiveness of suture anastomosis (SUA) versus stapled anastomosis (STA) in patients undergoing ileostomy closure. Randomized, controlled trials comparing the effectiveness of SUA versus STA in patients undergoing ileostomy closure were analyzed using RevMan(®), and combined outcomes were expressed as odds risk ratio (OR) and standardized mean difference (SMD). Four randomized, controlled trials that recruited 645 patients were retrieved from electronic databases. There were 327 patients in the STA group and 318 patients in the SUA group. There was significant heterogeneity among included trials. Operative time (SMD -1.02; 95 % CI -1.89, -0.15; z = 2.29; p infection, reoperation and readmission were similar following STA and SUA in patients undergoing ileostomy closure. Length of hospital stay was also similar between STA and SUA groups. In ileostomy closure, STA was associated with shorter operative time and lower risk of postoperative small bowel obstruction. However, STA and SUA were similar in terms of anastomotic leak, surgical site infection, readmission, reoperations and length of hospital stay.

  11. Comparative study of outcome measures and analysis methods for traumatic brain injury trials.

    Science.gov (United States)

    Alali, Aziz S; Vavrek, Darcy; Barber, Jason; Dikmen, Sureyya; Nathens, Avery B; Temkin, Nancy R

    2015-04-15

    Batteries of functional and cognitive measures have been proposed as alternatives to the Extended Glasgow Outcome Scale (GOSE) as the primary outcome for traumatic brain injury (TBI) trials. We evaluated several approaches to analyzing GOSE and a battery of four functional and cognitive measures. Using data from a randomized trial, we created a "super" dataset of 16,550 subjects from patients with complete data (n=331) and then simulated multiple treatment effects across multiple outcome measures. Patients were sampled with replacement (bootstrapping) to generate 10,000 samples for each treatment effect (n=400 patients/group). The percentage of samples where the null hypothesis was rejected estimates the power. All analytic techniques had appropriate rates of type I error (≤5%). Accounting for baseline prognosis either by using sliding dichotomy for GOSE or using regression-based methods substantially increased the power over the corresponding analysis without accounting for prognosis. Analyzing GOSE using multivariate proportional odds regression or analyzing the four-outcome battery with regression-based adjustments had the highest power, assuming equal treatment effect across all components. Analyzing GOSE using a fixed dichotomy provided the lowest power for both unadjusted and regression-adjusted analyses. We assumed an equal treatment effect for all measures. This may not be true in an actual clinical trial. Accounting for baseline prognosis is critical to attaining high power in Phase III TBI trials. The choice of primary outcome for future trials should be guided by power, the domain of brain function that an intervention is likely to impact, and the feasibility of collecting outcome data.

  12. A randomized controlled trial comparing split and subunit influenza vaccines in adults in Colombia

    Directory of Open Access Journals (Sweden)

    A. Morales

    2003-06-01

    Full Text Available In a two-center, comparative trial, 344 adults were randomly assigned to receive a single dose of inactivated split-virion (Imovax Gripeâ or sub-unit (Agrippal S1â influenza vaccine (1999-2000 formulations. For analysis, study groups were subdivided into adult (18-60 years old and elderly (over 60 years subjects. Blood was drawn immediately before and one month after vaccination, safety was evaluated using a blind-observer design based on reporting of solicited and unsolicited adverse events. Both vaccines were very well tolerated, had similar reactogenicity profiles, and elicited fewer reports of reactions in elderly individuals. Post-vaccination Imovax Gripeâ induced seroprotective antibody titers against the three vaccine strains in 94-99% of adults and 88-97% of elderly subjects, compared with 88-100% and 88-98%, respectively, of those given Agrippal S1â. In conclusion, the split-virion and sub-unit influenza vaccines had similar safety and reactogenicity profiles, and elicited satisfactory immunity in adult and elderly subjects. However, higher post-vaccination geometric mean titer (GMT values in response to the B strain were seen with the split vaccine Imovax Gripeâ, giving it a better overall immunogenicity.En un ensayo comparativo realizado en dos centros, se asignaron de manera aleatoria 344 adultos para recibir una dosis de vacuna contra la gripe de virus fraccionado inactivado (Imovax Gripeâ o de vacuna de subunidades (Agrippal S1â (formulaciones 1999-2000. Para el análisis, los grupos estudiados fueron subdivididos en adultos (18-60 años y ancianos (más de 60 años. La sangre fue extraída justo antes y un mes después de la vacunación. La inocuidad fue evaluada utilizando un informe sobre reacciones adversas, usando un diseño de observador a ciegas. Ambas vacunas fueron muy bien toleradas, con perfiles de reactogenicidad similares y desarrollaron escasas reacciones adversas en los individuos ancianos. La vacunación con

  13. Effect of a thiolated polymer on oral paclitaxel absorption and tumor growth in rats.

    Science.gov (United States)

    Föger, Florian; Malaivijitnond, Suchinda; Wannaprasert, Thanakul; Huck, Christian; Bernkop-Schnürch, Andreas; Werle, Martin

    2008-02-01

    The anticancer agent paclitaxel is currently commercially available only as an infusion due to its low oral bioavailability. An oral formulation would be highly beneficial for patients. Besides the low solubility, the main reason for the limited oral bioavailability of paclitaxel is that it is a substrate of the efflux pump P-glycoprotein (P-gp). Recently, it has been demonstrated that P-gp can be inhibited by thiolated polymers. In this study, an oral paclitaxel formulation based on thiolated polycarbophil was evaluated in vivo in wild-type rats and in mammary cancer-induced rats. The paclitaxel plasma level after a single administration of paclitaxel was observed for 12 h in healthy rats. Moreover, cancer-induced rats were treated weekly for 5 weeks with the novel formulation. It was demonstrated that (1) co-administration of thiolated polycarbophil significantly improved paclitaxel plasma levels, (2) a more constant pharmacokinetic profile could be achieved and (3) the tumor growth was reduced. These effects can most likely be attributed to P-gp inhibition. According to the achieved results, thiolated polymers are believed to be interesting tools for the delivery of P-gp substrates such as paclitaxel.

  14. Targeting metastatic breast cancer with ANG1005, a novel peptide-paclitaxel conjugate that crosses the blood-brain-barrier (BBB

    Directory of Open Access Journals (Sweden)

    Fei Li

    2017-03-01

    Full Text Available We devoted this short interview piece with Dr Shou-Ching Tang at Augusta University to feature some promising results from a clinical phase II trial on a novel brain-penetrating peptide-paclitaxel-conjugate, ANG1005, in treating brain metastatic breast cancer. These results were presented by Dr. Tang at the recent annual meeting of the European Society for Medical Oncology (ESMO 2016 Congress. This development heralds an important step forward towards the development of effective chemotherapeutic agents, which can cross the blood-brain-barrier and effectively treat and prevent the brain metastatic cancers.

  15. Is a comparative clinical trial for breast cancer tumor markers to monitor disease recurrence warranted? A value of information analysis.

    Science.gov (United States)

    Thariani, Rahber; Henry, Norah Lynn; Ramsey, Scott D; Blough, David K; Barlow, Bill; Gralow, Julie R; Veenstra, David L

    2013-05-01

    Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors. We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3-6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30-60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation.

  16. Postpartum perineal reapir performed by midwives: A randomised trial comparing two suture techniques for perineal repair leaving the skin unsutured

    DEFF Research Database (Denmark)

    Kindberg, Sara; Misan, Stehouwer; Hvidman, Lone

    2008-01-01

    Postpartum perineal repair performed by midwives: A randomised trial comparing two suture techniques leaving the skin unsutured. Objective      To compare a continuous suture technique to interrupted stitches using inverted knots for postpartum perineal repair of second-degree lacerations...... and episiotomies.   Design          A double blind randomised controlled trial.   Setting          A Danish university hospital with more than 4800 deliveries annually.   Population   400 healthy primiparous women with a vaginal delivery at term.   Method         Randomisation was computer-controlled. Structured...... healing, patient satisfaction, dyspareunia or need for resuturing. The continuous suture technique was significantly faster (15 min. vs. 17 min, p=0.03) and less suture material was used (1 vs. 2 packets, pskin unsutured...

  17. Biocatalysis of a Paclitaxel Analogue: Conversion of Baccatin III to N-Debenzoyl-N-(2-furoyl)paclitaxel and Characterization of an Amino Phenylpropanoyl CoA Transferase.

    Science.gov (United States)

    Thornburg, Chelsea K; Walter, Tyler; Walker, Kevin D

    2017-11-07

    In this study, we demonstrate an enzyme cascade reaction using a benzoate CoA ligase (BadA), a modified nonribosomal peptide synthase (PheAT), a phenylpropanoyltransferase (BAPT), and a benzoyltransferase (NDTNBT) to produce an anticancer paclitaxel analogue and its precursor from the commercially available biosynthetic intermediate baccatin III. BAPT and NDTNBT are acyltransferases on the biosynthetic pathway to the antineoplastic drug paclitaxel in Taxus plants. For this study, we addressed the recalcitrant expression of BAPT by expressing it as a soluble maltose binding protein fusion (MBP-BAPT). Further, the preparative-scale in vitro biocatalysis of phenylisoserinyl CoA using PheAT enabled thorough kinetic analysis of MBP-BAPT, for the first time, with the cosubstrate baccatin III. The turnover rate of MBP-BAPT was calculated for the product N-debenzoylpaclitaxel, a key intermediate to various bioactive paclitaxel analogues. MBP-BAPT also converted, albeit more slowly, 10-deacetylbaccatin III to N-deacyldocetaxel, a precursor of the pharmaceutical docetaxel. With PheAT available to make phenylisoserinyl CoA and kinetic characterization of MBP-BAPT, we used Michaelis-Menten parameters of the four enzymes to adjust catalyst and substrate loads in a 200-μL one-pot reaction. This multienzyme network produced a paclitaxel analogue N-debenzoyl-N-(2-furoyl)paclitaxel (230 ng) that is more cytotoxic than paclitaxel against certain macrophage cell types. Also in this pilot reaction, the versatile N-debenzoylpaclitaxel intermediate was made at an amount 20-fold greater than the N-(2-furoyl) product. This reaction network has great potential for optimization to scale-up production and is attractive in its regioselective O- and N-acylation steps that remove protecting group manipulations used in paclitaxel analogue synthesis.

  18. Informed consent from cognitively impaired persons participating in research trials: comparative law observations.

    Science.gov (United States)

    Petrini, Carlo

    2011-01-01

    This article addresses the ethical requirements to be considered when conducting clinical trials involving human subjects whose mental condition limits their ability to understand the information and to express fully autonomous and informed consent. It does not address other categories of vulnerable persons, such as children, or advanced directives concerning end-of-life care. There are many ethical issues entailed in clinical trials involving subjects with mental disabilities: how to obtain informed consent, balancing risks and benefits, balancing individual benefits with collective scientific and social interests, legal representation and many more. This article focuses on the issues surrounding the concept of minimal risk and the relationship between informed consent and risk. These issues are addressed with particular emphasis on the regulations adopted by the European Union and the federal government of the United States of America. The conclusion proposes a list of working criteria.

  19. Treatment of secondary hyperparathyroidism in haemodialysis patients: a randomised clinical trial comparing paricalcitol and alfacalcidol

    DEFF Research Database (Denmark)

    Hansen, Ditte; Brandi, Lisbet; Rasmussen, Knud

    2009-01-01

    BACKGROUND: Secondary hyperparathyroidism is a common feature in patients with chronic kidney disease. Its serious clinical consequences include renal osteodystrophy, calcific uremic arteriolopathy, and vascular calcifications that increase morbidity and mortality.Reduced synthesis of active vita...... in the risk of cardiovascular mortality depending on which vitamin D analog that are used. This has potential major importance for this group of patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00469599....... vitamin D contributes to secondary hyperparathyroidism. Therefore, this condition is managed with activated vitamin D. However, hypercalcemia and hyperphosphatemia limit the use of activated vitamin D.In Denmark alfacalcidol is the primary choice of vitamin D analog.A new vitamin D analog, paricalcitol...... and hyperphosphatemia are associated with increased cardiovascular mortality in patients with chronic kidney disease.If there is any difference in the ability of these two vitamin D analogs to decrease the secondary hyperparathyroidism without causing hypercalcemia and hyperphosphatemia, there may also be a difference...

  20. Informed consent from cognitively impaired persons participating in research trials: comparative law observations

    Directory of Open Access Journals (Sweden)

    Carlo Petrini

    2011-12-01

    Full Text Available This article addresses the ethical requirements to be considered when conducting clinical trials involving human subjects whose mental condition limits their ability to understand the information and to express fully autonomous and informed consent. It does not address other categories of vulnerable persons, such as children, or advanced directives concerning end-of-life care. There are many ethical issues entailed in clinical trials involving subjects with mental disabilities: how to obtain informed consent, balancing risks and benefits, balancing individual benefits with collective scientific and social interests, legal representation and many more. This article focuses on the issues surrounding the concept of minimal risk and the relationship between informed consent and risk. These issues are addressed with particular emphasis on the regulations adopted by the European Union and the federal government of the United States of America. The conclusion proposes a list of working criteria.

  1. Reducing Trunk Compensation in Stroke Survivors: A Randomized Crossover Trial Comparing Visual and Force Feedback Modalities.

    Science.gov (United States)

    Valdés, Bulmaro Adolfo; Schneider, Andrea Nicole; Van der Loos, H F Machiel

    2017-10-01

    To investigate whether the compensatory trunk movements of stroke survivors observed during reaching tasks can be decreased by force and visual feedback, and to examine whether one of these feedback modalities is more efficacious than the other in reducing this compensatory tendency. Randomized crossover trial. University research laboratory. Community-dwelling older adults (N=15; 5 women; mean age, 64±11y) with hemiplegia from nontraumatic hemorrhagic or ischemic stroke (>3mo poststroke), recruited from stroke recovery groups, the research group's website, and the community. In a single session, participants received augmented feedback about their trunk compensation during a bimanual reaching task. Visual feedback (60 trials) was delivered through a computer monitor, and force feedback (60 trials) was delivered through 2 robotic devices. Primary outcome measure included change in anterior trunk displacement measured by motion tracking camera. Secondary outcomes included trunk rotation, index of curvature (measure of straightness of hands' path toward target), root mean square error of hands' movement (differences between hand position on every iteration of the program), completion time for each trial, and posttest questionnaire to evaluate users' experience and system's usability. Both visual (-45.6% [45.8 SD] change from baseline, P=.004) and force (-41.1% [46.1 SD], P=.004) feedback were effective in reducing trunk compensation. Scores on secondary outcome measures did not improve with either feedback modality. Neither feedback condition was superior. Visual and force feedback show promise as 2 modalities that could be used to decrease trunk compensation in stroke survivors during reaching tasks. It remains to be established which one of these 2 feedback modalities is more efficacious than the other as a cue to reduce compensatory trunk movement. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  2. A proposed framework for evaluating and comparing efficacy estimates in clinical trials of new rotavirus vaccines.

    Science.gov (United States)

    Neuzil, Kathleen M; Zaman, K; Victor, John C

    2014-08-11

    Oral rotavirus vaccines have yielded different point estimates of efficacy when tested in different populations. While population and environmental factors may account for these differences, study design characteristics should also be considered. We review the study design elements of rotavirus vaccine trials that may affect point estimates of efficacy, and propose a framework for evaluating new rotavirus vaccines. Copyright © 2014. Published by Elsevier Ltd.

  3. Single-Staged Compared With Multi-Staged PCI in Multivessel NSTEMI Patients: The SMILE Trial.

    Science.gov (United States)

    Sardella, Gennaro; Lucisano, Luigi; Garbo, Roberto; Pennacchi, Mauro; Cavallo, Erika; Stio, Rocco Edoardo; Calcagno, Simone; Ugo, Fabrizio; Boccuzzi, Giacomo; Fedele, Francesco; Mancone, Massimo

    2016-01-26

    A lack of clarity exists about the role of complete coronary revascularization in patients presenting with non-ST-segment elevation myocardial infarction. The aim of our study was to compare long-term outcomes in terms of major adverse cardiovascular and cerebrovascular events of 2 different complete coronary revascularization strategies in patients with non-ST-segment elevation myocardial infarction and multivessel coronary artery disease: 1-stage percutaneous coronary intervention (1S-PCI) during the index procedure versus multistage percutaneous coronary intervention (MS-PCI) complete coronary revascularization during the index hospitalization. In the SMILE (Impact of Different Treatment in Multivessel Non ST Elevation Myocardial Infarction Patients: One Stage Versus Multistaged Percutaneous Coronary Intervention) trial, 584 patients were randomly assigned in a 1:1 manner to 1S-PCI or MS-PCI. The primary study endpoint was the incidence of major adverse cardiovascular and cerebrovascular events, which were defined as cardiac death, death, reinfarction, rehospitalization for unstable angina, repeat coronary revascularization (target vessel revascularization), and stroke at 1 year. The occurrence of the primary endpoint was significantly lower in the 1-stage group (1S-PCI: n = 36 [13.63%] vs. MS-PCI: n = 61 [23.19%]; hazard ratio [HR]: 0.549 [95% confidence interval (CI): 0.363 to 0.828]; p = 0.004). The 1-year rate of target vessel revascularization was significantly higher in the MS-PCI group (1S-PCI: n = 22 [8.33%] vs. MS-PCI: n = 40 [15.20%]; HR: 0.522 [95% CI: 0.310 to 0.878]; p = 0.01; p log-rank = 0.013). When the analyses were limited to cardiac death (1S-PCI: n = 9 [3.41%] vs. MS-PCI: n = 14 [5.32%]; HR: 0.624 [95% CI: 0.270 to 1.441]; p = 0.27) and myocardial infarction (1S-PCI: n = 7 [2.65%] vs. MS-PCI: n = 10 [3.80%]; HR: 0.678 [95% CI: 0.156 to 2.657]; p = 0.46), no significant differences were observed between groups. In multivessel

  4. A combination of subcuticular suture and sterile Micropore tape compared with conventional interrupted sutures for skin closure. A controlled trial.

    Science.gov (United States)

    Taube, M.; Porter, R. J.; Lord, P. H.

    1983-01-01

    We have conducted a controlled trial to compare skin closure using conventional interrupted sutures with a combination of subcuticular suture and sterile Micropore tape in 169 patients undergoing appendicectomy, inguinal herniorrhaphy, or saphenofemoral ligation. We have found that the combination technique consistently gives a better cosmetic result and that the tape acts well as a dressing, is convenient, and is well tolerated by patients. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6344732

  5. A novel comparative effectiveness study of Tai Chi versus aerobic exercise for fibromyalgia: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Wang, Chenchen; McAlindon, Timothy; Fielding, Roger A; Harvey, William F; Driban, Jeffrey B; Price, Lori Lyn; Kalish, Robert; Schmid, Anna; Scott, Tammy M; Schmid, Christopher H

    2015-01-30

    Fibromyalgia is a chronic musculoskeletal pain syndrome that causes substantial physical and psychological impairment and costs the US healthcare system over $25 billion annually. Current pharmacological therapies may cause serious adverse effects, are expensive, and fail to effectively improve pain and function. Finding new and effective non-pharmacological treatments for fibromyalgia patients is urgently needed. We are currently conducting the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise (a recommended component of the current standard of care) in a large fibromyalgia population. This article describes the design and conduct of this trial. A single-center, 52-week, randomized controlled trial of Tai Chi versus aerobic exercise is being conducted at an urban tertiary medical center in Boston, Massachusetts. We plan to recruit 216 patients with fibromyalgia. The study population consists of adults ≥21 years of age with fibromyalgia who meet American College of Rheumatology 1990 and 2010 diagnostic criteria. Participants are randomized to one of four Tai Chi intervention groups: 12 or 24 weeks of supervised Tai Chi held once or twice per week, or a supervised aerobic exercise control held twice per week for 24 weeks. The primary outcome is the change in Revised Fibromyalgia Impact Questionnaire total score from baseline to 24 weeks. Secondary outcomes include measures of widespread pain, symptom severity, functional performance, balance, muscle strength and power, psychological functioning, sleep quality, self-efficacy, durability effects, and health-related quality of life at 12, 24, and 52 week follow-up. This study is the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise in a large fibromyalgia population with long-term follow up. We present here a robust and well-designed trial to determine the optimal frequency and duration of a supervised Tai Chi intervention with regard to short

  6. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-01-01

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis. PMID:24549172

  7. Paclitaxel-induced apoptosis is BAK-dependent, but BAX and BIM-independent in breast tumor.

    Directory of Open Access Journals (Sweden)

    Anna V Miller

    Full Text Available Paclitaxel (Taxol-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim(-/- MEFs (mouse embryonic fibroblasts, the bim(-/- mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak (-/- MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel sensitivity was not affected in bax(-/- MEFs or in human breast cancer cells in which BAX was down-regulated, suggesting that paclitaxel-induced apoptosis is BAK-dependent, but BAX-independent. In human breast cancer cells, paclitaxel treatment resulted in MCL-1 degradation which was prevented by a proteasome inhibitor, MG132. A Cdk inhibitor, roscovitine, blocked paclitaxel-induced MCL-1 degradation and apoptosis, suggesting that Cdk activation at mitotic arrest could induce subsequent MCL-1 degradation in a proteasome-dependent manner. BAK was associated with MCL-1 in untreated cells and became activated in concert with loss of MCL-1 expression and its release from the complex. Our data suggest that BAK is the mediator of paclitaxel-induced apoptosis and could be an alternative target for overcoming paclitaxel resistance.

  8. CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

    Science.gov (United States)

    Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

    2014-08-01

    Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma.

    Science.gov (United States)

    Mukherjee, Somnath; Hurt, Christopher Nicholas; Gwynne, Sarah; Sebag-Montefiore, David; Radhakrishna, Ganesh; Gollins, Simon; Hawkins, Maria; Grabsch, Heike I; Jones, Gareth; Falk, Stephen; Sharma, Ricky; Bateman, Andrew; Roy, Rajarshi; Ray, Ruby; Canham, Jo; Griffiths, Gareth; Maughan, Tim; Crosby, Tom

    2017-03-01

    Oxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer. A non-blinded, randomised (1:1 via a centralised computer system), 'pick a winner' phase II trial. Patients with resectable oesophageal adenocarcinoma ≥ cT3 and/or ≥ cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m 2  day 1, 15, 29; capecitabine 625 mg/m 2 bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m 2  day 1, 8, 15, 22, 29). Radiotherapy dose was 45 Gy/25 fractions/5 weeks. Both arms received induction OxCap chemotherapy (2 × 3 week cycles of oxaliplatin 130 mg/m 2  day 1, capecitabine 625 mg/m 2 bd days 1-21). Surgery was performed 6-8 weeks after nCRT. Primary end-point was pathological complete response (pCR). Secondary end-points included toxicity, surgical morbidity/mortality, resection rate and overall survival. Based on pCR ≤ 15% not warranting future investigation, but pCR ≥ 35% would, 76 patients (38/arm) gave 90% power (one-sided alpha 10%), implying that arm(s) having ≥10 pCR out of first 38 patients could be considered for phase III trials. ClinicalTrials.gov: NCT01843829. Funder: Cancer Research UK (C44694/A14614). Eighty five patients were randomised between October 2013 and February 2015 from 17 UK centres. Three of 85 (3.5%) died during induction chemotherapy. Seventy-seven patients (OxCapRT = 36; CarPacRT = 41) underwent surgery. The 30-d post-operative mortality was 2/77 (2.6%). Grade III/IV toxicity was comparable between arms, although neutropenia was higher in the CarPacRT arm (21.4% versus 2.6%, p = 0.01). Twelve of 41 (29.3%) (10 of first 38 patients) and 4/36 (11.1%) achieved pCR in the CarPacRT and OxcapRT arms, respectively. Corresponding R0 resection rates were 33/41 (80.5%) and 26/36 (72.2%), respectively. Both regimens were well tolerated. Only CarPacRT passed the predefined p

  10. Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study

    Science.gov (United States)

    MacLaughlan David, Shannon; Salzillo, Sandra; Bowe, Patrick; Scuncio, Sandra; Malit, Bridget; Raker, Christina; Gass, Jennifer S; Granai, C O; Dizon, Don S

    2013-01-01

    Objectives To compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a drug with a complementary or alternative method (CAM). Design Prospective randomised trial. Setting Breast health centre of a tertiary care centre. Participants 15 women with a personal history of breast cancer or an increased risk of breast cancer who reported at least one daily hot flash. Interventions Gabapentin 900 mg daily in three divided doses (control) compared with standardised hypnotherapy. Participation lasted 8 weeks. Outcome measures The primary endpoints were the number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS). Results 27 women were randomised and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After 8 weeks, the median number of daily hot flashes was reduced by 33.3% in the gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group. There were no statistically significant differences between groups. Conclusions Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A definitive trial evaluating traditional interventions against CAM methods is feasible, but not without challenges. Further studies aimed at defining evidence-based recommendations for CAM are necessary. Trial registration clinicaltrials.gov (NCT00711529). PMID:24022390

  11. COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer

    DEFF Research Database (Denmark)

    Buunen, M; Bonjer, H J; Hop, W C J

    2009-01-01

    clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy...... analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal...

  12. A randomized trial comparing bladder volume consistency during fractionated prostate radiation therapy

    LENUS (Irish Health Repository)

    Mullaney, L.

    2014-01-10

    Organ motion is a contributory factor to the variation in location of the prostate and organs at risk during a course of fractionated prostate radiation therapy (RT). A prospective randomized controlled trial was designed with the primary endpoint to provide evidence-based bladder-filling instructions to achieve a consistent bladder volume (BV) and thus reduce the bladder-related organ motion. The secondary endpoints were to assess the incidence of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity for patients and patients’ satisfaction with the bladder-filling instructions.

  13. Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a multicentre randomised study comparing indwelling pleural catheter versus talc pleurodesis

    Science.gov (United States)

    Fysh, Edward T H; Thomas, Rajesh; Read, Catherine A; Lam, Ben C H; Yap, Elaine; Horwood, Fiona C; Lee, Pyng; Piccolo, Francesco; Shrestha, Ranjan; Garske, Luke A; Lam, David C L; Rosenstengel, Andrew; Bint, Michael; Murray, Kevin; Smith, Nicola A; Lee, Y C Gary

    2014-01-01

    Introduction Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients’ remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. Methods and analysis The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. Ethics and dissemination The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The

  14. A pragmatic, multicentre, randomised controlled trial comparing stapled haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease (eTHoS): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Watson, Angus J M; Bruhn, Hanne; MacLeod, Kathleen; McDonald, Alison; McPherson, Gladys; Kilonzo, Mary; Norrie, John; Loudon, Malcolm A; McCormack, Kirsty; Buckley, Brian; Brown, Steven; Curran, Finlay; Jayne, David; Rajagopal, Ramesh; Cook, Jonathan A

    2014-11-11

    Current interventions for haemorrhoidal disease include traditional haemorrhoidectomy (TH) and stapled haemorrhoidopexy (SH) surgery. However, uncertainty remains as to how they compare from a clinical, quality of life (QoL) and economic perspective. The study is therefore designed to determine whether SH is more effective and more cost-effective, compared with TH. eTHoS (either Traditional Haemorrhoidectomy or Stapled Haemorrhoidopexy for Haemorrhoidal Disease) is a pragmatic, multicentre, randomised controlled trial. Currently, 29 secondary care centres are open to recruitment. Patients, aged 18 year or older, with circumferential haemorrhoids grade II to IV, are eligible to take part. The primary clinical and economic outcomes are QoL profile (area under the curve derived from the EuroQol Group's 5 Dimension Health Status Questionnaire (EQ-5D) at all assessment points) and incremental cost per quality adjusted life year (QALY) based on the responses to the EQ-5D at 24 months. The secondary outcomes include a comparison of the SF-36 scores, pain and symptoms sub-domains, disease recurrence, complication rates and direct and indirect costs to the National Health Service (NHS). A sample size of n =338 per group has been calculated to provide 90% power to detect a difference in the mean area under the curve (AUC) of 0.25 standard deviations derived from EQ-5D score measurements, with a two-sided significance level of 5%. Allowing for non-response, 400 participants will be randomised per group. Randomisation will utilise a minimisation algorithm that incorporates centre, grade of haemorrhoidal disease, baseline EQ-5D score and gender. Blinding of participants and outcome assessors is not attempted. This is one of the largest trials of its kind. In the United Kingdom alone, 29,000 operations for haemorrhoidal disease are done annually. The trial is therefore designed to give robust evidence on which clinicians and health service managers can base management decisions

  15. The effects of honey compared to silver sulfadiazine for the treatment of burns: A systematic review of randomized controlled trials.

    Science.gov (United States)

    Aziz, Zoriah; Abdul Rasool Hassan, Bassam

    2017-02-01

    Evidence from animal studies and trials suggests that honey may accelerate wound healing. The objective of this review was to assess the effects of honey compared with silver dressings on the healing of burn wounds. Relevant databases for randomized controlled trials (RCTs) of honey compared with silver sulfadiazine (SSD) were searched. The quality of the selected trials was assessed using the Cochrane Risk of Bias Assessment Tool. The primary endpoints considered were wound healing time and the number of infected wounds rendered sterile. Nine RCTs met the inclusion criteria. Based on moderate quality evidence there was a statistically significant difference between the two groups, favoring honey in healing time (MD -5.76days, 95% CI -8.14 to -3.39) and the proportions of infected wounds rendered sterile (RR 2.59; 95% CI 1.58-2.88). The available evidence suggests that honey dressings promote better wound healing than silver sulfadiazine for burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  16. Adaptation and dissemination of an evidence-based obesity prevention intervention: design of a comparative effectiveness trial.

    Science.gov (United States)

    Buscemi, Joanna; Odoms-Young, Angela; Stolley, Melinda L; Blumstein, Lara; Schiffer, Linda; Berbaum, Michael L; McCaffrey, Jennifer; Montoya, Anastasia McGee; Braunschweig, Carol; Fitzgibbon, Marian L

    2014-07-01

    Low-income youth are at increased risk for excess weight gain. Although evidence-based prevention programs exist, successful adaptation to provide wide dissemination presents a challenge. Hip-Hop to Health (HH) is a school-based obesity prevention intervention that targets primarily preschool children of low-income families. In a large randomized controlled trial, HH was found to be efficacious for prevention of excessive weight gain. The Expanded Food and Nutrition Education Program (EFNEP) and the Supplemental Nutrition Assistance Program-Education (SNAP-Ed) are USDA-funded nutrition education programs offered to low-income families, and may provide an ideal platform for the wide dissemination of evidence-based obesity prevention programs. A research-practice partnership was established in order to conduct formative research to guide the adaptation and implementation of HH through EFNEP and SNAP-Ed. We present the design and method of a comparative effectiveness trial that will determine the efficacy of HH when delivered by peer educators through these programs compared to the standard EFNEP and SNAP-Ed nutrition education (NE) curriculum. Results from this trial will inform larger scale dissemination. The dissemination of HH through government programs has the potential to increase the reach of efficacious obesity prevention programs that target low-income children and families. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. A comparative trial of psychotherapy and pharmacotherapy for "pure" dysthymic patients.

    Science.gov (United States)

    Markowitz, John C; Kocsis, James H; Bleiberg, Kathryn L; Christos, Paul J; Sacks, Michael

    2005-12-01

    Psychotherapy of "pure" dysthymic disorder remains understudied. This article reports outcomes of an acute randomized trial of 94 subjects treated for 16 weeks with either interpersonal psychotherapy (IPT), brief supportive psychotherapy (BSP), sertraline, or sertraline plus IPT. Recruited by clinical referral and advertising, subjects met DSM-IV criteria for early onset dysthymic disorder, with no episode of major depression in the prior six months. They were randomly assigned to one of four 16-week treatments, with options for crossover or continuation treatment. Results were analyzed from the intention-to-treat sample by ANCOVA, controlling for baseline depressive severity. Subjects improved in all conditions over time, with the cells including sertraline pharmacotherapy showing superiority over psychotherapy alone for response and remission. Response rates were 58% for sertraline alone, 57% for combined treatment, 35% for IPT, and 31% for BSP. The study was underpowered and may have employed too "active" a control condition. Follow-up data were unobtainable. In this acute trial for "pure" dysthymic disorder, sertraline with or without IPT showed advantages relative to IPT and BSP. Methodological difficulties may have limited differential outcome findings. This study bolsters a small but growing literature on the treatment of dysthymic disorder, suggesting that pharmacotherapy may acutely benefit patients more than psychotherapy.

  18. A 5-year randomized trial to compare 1 or 2 implants for implant overdentures.

    Science.gov (United States)

    Bryant, S R; Walton, J N; MacEntee, M I

    2015-01-01

    The hypothesis of this 5-y randomized clinical trial was that there would be no significant difference in the satisfaction of edentulous participants with removable complete overdentures attached to 1 or 2 mandibular implants. Secondary aims were to test changes in satisfaction between and within the groups from baseline to 5 y and differences between the groups in implant survival and prosthodontic maintenance over 5 y. Each of the 86 participants (mean age, 67 y) was randomly allocated to receive either 1 implant in the midline (group 1) or 2 implants in the canine areas (group 2) attached to a mandibular overdenture opposing a maxillary complete denture. Satisfaction was self-assessed by participants on a visual analog scale at baseline prior to implants, as well as at 2 mo and 1, 3, and 5 y with implant overdentures, whereas implant survival and prosthodontic maintenance were assessed by clinical examination. After 5 y, 29 participants in group 1 and 33 in group 2 were available, with most dropouts due to death. Satisfaction with the implant denture after 5 y was significantly (P overdentures retained by 1 implant or 2 implants. Additional research is required to confirm long-term treatment effectiveness of single-implant dentures and the implications of prosthetic maintenance with implant overdentures (ClinicalTrials.gov: NCT02117856). © International & American Associations for Dental Research 2014.

  19. Design, Synthesis and Applications of Hyaluronic Acid-Paclitaxel Bioconjugatesâ€

    Directory of Open Access Journals (Sweden)

    Rinaldo Marini Bettolo

    2008-02-01

    Full Text Available Paclitaxel (1a, a well known antitumor agent adopted mainly for the treatmentof breast and ovarian cancer, suffers from significant disadvantages such as low solubility,certain toxicity and specific drug-resistance of some tumor cells. To overcome theseproblems extensive research has been carried out. Among the various proposed strategies,the conjugation of paclitaxel (1a to a biocompatible polymer, such as hyaluronic acid(HA, 2, has also been considered. Coupling a bioactive compound to a biocompatiblepolymer offers, in general, many advantages such as better drug solubilization, betterstabilization, specific localization and controlled release. Hereafter the design, synthesisand applications of hyaluronic acid-paclitaxel bioconjugates are reviewed. An overview ofHA-paclitaxel combinations is also given.

  20. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial

    DEFF Research Database (Denmark)

    Crivellari, D.; Sun, Z.; Coates, A.S.

    2008-01-01

    PURPOSE: To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial. METHODS: This report includes the 4,922 patients allocated to 5 years...... of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were...... had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy Udgivelsesdato: 2008/4/20...

  1. The Head Injury Retrieval Trial (HIRT): a single-centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics only.

    Science.gov (United States)

    Garner, Alan A; Mann, Kristy P; Fearnside, Michael; Poynter, Elwyn; Gebski, Val

    2015-11-01

    Advanced prehospital interventions for severe brain injury remains controversial. No previous randomised trial has been conducted to evaluate additional physician intervention compared with paramedic only care. Participants in this prospective, randomised controlled trial were adult patients with blunt trauma with either a scene GCS score definition), or GCSdefinition). Patients were randomised to either standard ground paramedic treatment or standard treatment plus a physician arriving by helicopter. Patients were evaluated by 30-day mortality and 6-month Glasgow Outcome Scale (GOS) scores. Due to high non-compliance rates, both intention-to-treat and as-treated analyses were preplanned. 375 patients met the original definition, of which 197 was allocated to physician care. Differences in the 6-month GOS scores were not significant on intention-to-treat analysis (OR 1.11, 95% CI 0.74 to 1.66, p=0.62) nor was the 30-day mortality (OR 0.91, 95% CI 0.60 to 1.38, p=0.66). As-treated analysis showed a 16% reduction in 30-day mortality in those receiving additional physician care; 60/195 (29%) versus 81/180 (45%), pdefinition, of which 182 were allocated to physician care. The 6-month GOS scores were not significantly different on intention-to-treat analysis (OR 1.14, 95% CI 0.73 to 1.75, p=0.56) nor was the 30-day mortality (OR 1.05, 95% CI 0.66 to 1.66, p=0.84). As-treated analyses were also not significantly different. This trial suggests a potential mortality reduction in patients with blunt trauma with GCSdefinition only). Confirmatory studies which also address non-compliance issues are needed. NCT00112398. 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.

  2. Pretreatment Pokemon Level as a Predictor of Response to Cisplatin and Paclitaxel in Patients with Unresectable Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Zhang, Quan-Le; Xing, Xi-Zhi; Li, Feng-Yan; Xing, Ya-Juan; Li, Jing

    2015-01-01

    We firstly investigated the expression of Pokemon in patients with non-small cell lung cancer (NSCLC), then characterized the role of Pokemon in evaluating the response to combined cisplatin and paclitaxel chemotherapy and prognosis. In this study, 61 patients with previously untreated locally advanced or metastatic NSCLC were treated with a combination chemotherapy comprising cisplatin and paclitaxel. The correlation between serum expression of Pokemon and effectiveness of chemotherapy was assessed. The expression level of Pokemon in NSCLC patients was higher than that in healthy controls (p = 0.000), and was correlated with tumor size and TNM stage (p Pokemon levels in excess of 135.09 ng/ml compared to those with Pokemon levels below 135.09 ng/ml (p = 0.013). Pokemon ≥ 135.09 ng/ml was an independent risk factor for survival time in NSCLC patients undergoing combination chemotherapy (p = 0.018). The serum level of Pokemon correlated with efficacy of cisplatin and paclitaxel combination chemotherapy and survival time, which indicated that Pokemon may be a potentially useful biomarker for predicting treatment effectiveness of first-line chemotherapy and prognosis in NSCLC. © 2015 S. Karger GmbH, Freiburg.

  3. Dropout Rates in Randomized Clinical Trials of Antipsychotics: A Meta-analysis Comparing First- and Second-Generation Drugs and an Examination of the Role of Trial Design Features

    OpenAIRE

    Rabinowitz, Jonathan; Levine, Stephen Z.; Barkai, Orna; Davidov, Ori

    2008-01-01

    Dropout is often used as an outcome measure in clinical trials of antipsychotic medication. Previous research is inconclusive regarding (a) differences in dropout rates between first- and second-generation antipsychotic medications and (b) how trial design features reduce dropout. Meta-analysis of randomized controlled trials (RCTs) of antipsychotic medication was conducted to compare dropout rates for first- and second-generation antipsychotic drugs and to examine how a broad range of design...

  4. Impact of CYP2C8*3 on paclitaxel clearance in ovarian cancer patients

    OpenAIRE

    Bergmann, Troels Korshøj; Vach, Werner; Gréen, Henrik; Karlsson, Mats; Friberg, Lena; Nielsen, Flemming; Pedersen, Rasmus Steen; Mirza, Mansoor Raza; Andersen, Charlotte Brasch; Brøsen, Kim

    2009-01-01

    BackgroundToxicity and therapeutic effects of paclitaxel vary greatly between patients and remain a clinically relevant problem with regard to the handling of dose delay/reduction or termination of treatment. We investigated the notion that single nucleotide polymorphisms (SNPs) in CYP2C8 could be partly responsible for this variation. Paclitaxel is mainly metabolized by CYP2C8; SNPs have been investigated in this context before but conclusions are still lacking. We present a prospective stud...

  5. Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

    Science.gov (United States)

    Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

    2018-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Global Inhibition of Reactive Oxygen Species (ROS) Inhibits Paclitaxel-Induced Painful Peripheral Neuropathy

    OpenAIRE

    Fidanboylu, Mehmet; Griffiths, Lisa A.; Flatters, Sarah J. L.

    2011-01-01

    Paclitaxel (Taxol (R)) is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS...

  7. Genomic signatures for paclitaxel and gemcitabine resistance in breast cancer derived by machine learning.

    Science.gov (United States)

    Dorman, Stephanie N; Baranova, Katherina; Knoll, Joan H M; Urquhart, Brad L; Mariani, Gabriella; Carcangiu, Maria Luisa; Rogan, Peter K

    2016-01-01

    Increasingly, the effectiveness of adjuvant chemotherapy agents for breast cancer has been related to changes in the genomic profile of tumors. We investigated correspondence between growth inhibitory concentrations of paclitaxel and gemcitabine (GI50) and gene copy number, mutation, and expression first in breast cancer cell lines and then in patients. Genes encoding direct targets of these drugs, metabolizing enzymes, transporters, and those previously associated with chemoresistance to paclitaxel (n = 31 genes) or gemcitabine (n = 18) were analyzed. A multi-factorial, principal component analysis (MFA) indicated expression was the strongest indicator of sensitivity for paclitaxel, and copy number and expression were informative for gemcitabine. The factors were combined using support vector machines (SVM). Expression of 15 genes (ABCC10, BCL2, BCL2L1, BIRC5, BMF, FGF2, FN1, MAP4, MAPT, NFKB2, SLCO1B3, TLR6, TMEM243, TWIST1, and CSAG2) predicted cell line sensitivity to paclitaxel with 82% accuracy. Copy number profiles of 3 genes (ABCC10, NT5C, TYMS) together with expression of 7 genes (ABCB1, ABCC10, CMPK1, DCTD, NME1, RRM1, RRM2B), predicted gemcitabine response with 85% accuracy. Expression and copy number studies of two independent sets of patients with known responses were then analyzed with these models. These included tumor blocks from 21 patients that were treated with both paclitaxel and gemcitabine, and 319 patients on paclitaxel and anthracycline therapy. A new paclitaxel SVM was derived from an 11-gene subset since data for 4 of the original genes was unavailable. The accuracy of this SVM was similar in cell lines and tumor blocks (70-71%). The gemcitabine SVM exhibited 62% prediction accuracy for the tumor blocks due to the presence of samples with poor nucleic acid integrity. Nevertheless, the paclitaxel SVM predicted sensitivity in 84% of patients with no or minimal residual disease. Copyright © 2015 Federation of European Biochemical Societies

  8. LBA50 - Influence of concomitant clopidogrel consumption on development of paclitaxel-associated toxicity: A pharmacoepidemiological study

    DEFF Research Database (Denmark)

    K, Agergaard; Mau-Sørensen, M; Stage, Tore Bjerregaard

    clopidogrel to a metabolite, which is a strong inhibitor of CYP2C8. To determine if this interaction has clinical relevance, we investigated whether concomitant clopidogrel and paclitaxel was associated with severe paclitaxel toxicity, primarily peripheral sensory neuropathy. Methods Patients concomitantly...... from medical charts by reviewers partially blinded to clopidogrel exposure. The association of clopidogrel use and development of paclitaxel induced neuropathy was evaluated over accumulated paclitaxel dose with censoring after 1500 mg using Cox-regression analysis with adjustment for high intensity...... neuropathy or worse. Clopidogrel use was associated with increased risk of neuropathy with hazard ratios of 1.7 (95% CI 0.9-3.0), 2.0 (1.0-3.9) and 2.3 (1.1-4.5) in overall unadjusted, high intensity paclitaxel unadjusted and high intensity paclitaxel full adjusted analyses, respectively. Conclusions...

  9. Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60 year old Caucasian woman with ovarian carcinoma

    DEFF Research Database (Denmark)

    Bergmann, Troels K; Filppula, Anne M; Launiainen, Terhi

    2015-01-01

    % of the cohort geometric mean (385 L/h; range 176-726). She was hospitalised thrice, developed severe neuropathy and paclitaxel treatment was subsequently discontinued. In vitro, 30 min preincubation with 100 μM clopidogrel acyl-β-D-glucuronide inhibited the depletion rate of 0.5 μM paclitaxel by 51......AIM: The aim of this case report is to describe a novel pharmacokinetic drug-drug interaction between the antiplatelet agent clopidogrel and the antineoplastic agent paclitaxel. METHODS: The patient was identified in a previously described cohort of 93 patients with ovarian carcinoma treated...... with paclitaxel. The effect of clopidogrel acyl-β-D-glucuronide on the metabolism of paclitaxel was assessed in human liver microsomes. The analysis of clopidogrel in plasma and the quantification of paclitaxel and 6α-hydroxypaclitaxel in in vitro samples were performed by liquid chromatography tandem mass...

  10. Rationale for a randomized controlled trial comparing two prophylaxis regimens in adults with severe hemophilia A: the Hemophilia Adult Prophylaxis Trial

    Science.gov (United States)

    Ragni, Margaret V

    2011-01-01

    A major goal of comprehensive hemophilia care is to prevent occurrence of bleeds by prophylaxis or regular preventive factor, one or more times weekly. Although prophylaxis is effective in reducing bleeding and joint damage in children, whether it is necessary to continue into adulthood is not known. The purpose of this article is to describe a Phase III randomized controlled trial to evaluate prophylaxis comparing two dose regimens in adults with severe hemophilia A. I hypothesize that adults with mature cartilage and joints are less susceptible to joint bleeds and joint damage, and that once-weekly recombinant factor VIII prophylaxis, with up to two rescue doses per week, is as effective as thrice-weekly prophylaxis in reducing bleeding frequency, but less costly and more acceptable, with higher quality of life. The ultimate goal of this project is to determine whether once-weekly prophylaxis is any worse than thrice-weekly prophylaxis in reducing joint bleeding frequency, while potentially utilizing less factor, at lower cost, leading to a better quality of life. This is an innovative concept, as it challenges the current paradigm of thrice-weekly prophylaxis in adults, which is based on dosing in children. Furthermore, this trial will assess interdose thrombin generation, a novel tissue factor-based assay of hemostasis, to determine if individualized thrombin generation can predict more individualized prophylaxis dosing, which would be practice changing. PMID:21939418

  11. Randomized clinical trial comparing an oral carbohydrate beverage with placebo before laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Bisgaard, T; Kristiansen, V B; Hjortsø, N C

    2004-01-01

    BACKGROUND: Preoperative oral carbohydrate can attenuate postoperative insulin resistance and catabolism, and may have the potential to improve postoperative recovery. There are no data from randomized studies on postoperative clinical outcome after specific surgical procedures. This study...... evaluated the clinical effects of a preoperative carbohydrate beverage in patients undergoing laparoscopic cholecystectomy. METHODS: Ninety-four patients undergoing laparoscopic cholecystectomy were included in a randomized clinical trial. Patients were randomized to receive 800 ml of an iso-osmolar 12.......5 per cent carbohydrate-rich beverage the evening before operation (100 g carbohydrate) and another 400 ml (50 g carbohydrate) 2 h before initiation of anaesthesia, or the same volume of a placebo beverage. The primary endpoint was general well-being the day after operation. Patients were evaluated from...

  12. Surgical site infection: an observer-blind, randomized trial comparing electrocautery and conventional scalpel.

    Science.gov (United States)

    Rongetti, Regiane Ladislau; Oliveira e Castro, Paulo de Tarso; Vieira, Renê Aloisio da Costa; Serrano, Sérgio Vicente; Mengatto, Mariana Fabro; Fregnani, José Humberto Tavares Guerreiro

    2014-01-01

    To evaluate the incidence of surgical site infection (SSI) based on the type of scalpel used for incisions in the skin and in subcutaneous tissues. Observer-blind, randomized equivalence clinical trial with two arms (electrocautery versus conventional scalpel) which evaluated 133 women undergoing elective abdominal gynecologic oncology surgery. A simple randomization stratified by body mass index (BMI: 30 kg/m(2)) was carried out. Women were evaluated at 14 and 30 days following the operation. A multivariate analysis was performed in order to check whether the type of scalpel would be a risk factor for SSI. Group arms were balanced for all variables, excepted for surgical time, which was significantly higher in the electrocautery group (mean: 161.1 versus 203.5 min, P = 0.029). The rates of SSI were 7.4% and 9.7%, respectively, for the conventional scalpel and electrocautery groups (P = 0.756). The exploratory multivariate model identified body mass index ≥30 kg/m(2) (OR = 24.2, 95% CI: 2.8-212.1) and transverse surgical incision (OR = 8.1, 95% CI: 1.5-42.6) as independent risk factors for SSI. The type of scalpel used in surgery, when adjusted for these variables and the surgery time, was not a risk factor for SSI. This study showed that the SSI rates for conventional scalpel and electrocautery were not significantly different. These results were consistent with others reported in the literature and would not allow a surgeon to justify scalpel choice based on SSI. NCT01410175 (Clinical Trials - NIH). Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  13. The Head Injury Retrieval Trial (HIRT): a single-centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics only

    Science.gov (United States)

    Garner, Alan A; Mann, Kristy P; Fearnside, Michael; Poynter, Elwyn; Gebski, Val

    2015-01-01

    Background Advanced prehospital interventions for severe brain injury remains controversial. No previous randomised trial has been conducted to evaluate additional physician intervention compared with paramedic only care. Methods Participants in this prospective, randomised controlled trial were adult patients with blunt trauma with either a scene GCS score <9 (original definition), or GCS<13 and an Abbreviated Injury Scale score for the head region ≥3 (modified definition). Patients were randomised to either standard ground paramedic treatment or standard treatment plus a physician arriving by helicopter. Patients were evaluated by 30-day mortality and 6-month Glasgow Outcome Scale (GOS) scores. Due to high non-compliance rates, both intention-to-treat and as-treated analyses were preplanned. Results 375 patients met the original definition, of which 197 was allocated to physician care. Differences in the 6-month GOS scores were not significant on intention-to-treat analysis (OR 1.11, 95% CI 0.74 to 1.66, p=0.62) nor was the 30-day mortality (OR 0.91, 95% CI 0.60 to 1.38, p=0.66). As-treated analysis showed a 16% reduction in 30-day mortality in those receiving additional physician care; 60/195 (29%) versus 81/180 (45%), p<0.01, Number needed to treat =6. 338 patients met the modified definition, of which 182 were allocated to physician care. The 6-month GOS scores were not significantly different on intention-to-treat analysis (OR 1.14, 95% CI 0.73 to 1.75, p=0.56) nor was the 30-day mortality (OR 1.05, 95% CI 0.66 to 1.66, p=0.84). As-treated analyses were also not significantly different. Conclusions This trial suggests a potential mortality reduction in patients with blunt trauma with GCS<9 receiving additional physician care (original definition only). Confirmatory studies which also address non-compliance issues are needed. Trial registration number NCT00112398. PMID:25795741

  14. Construction of hydroxypropyl-{beta}-cyclodextrin copolymer nanoparticles and targeting delivery of paclitaxel

    Energy Technology Data Exchange (ETDEWEB)

    Miao Qinghua; Li Suping; Han Siyuan [National Center for Nanoscience and Technology of China, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety (China); Wang Zhi, E-mail: wangzhi@jlu.edu.cn [Jilin University, Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education (China); Wu Yan, E-mail: wuy@nanoctr.cn; Nie Guangjun, E-mail: niegj@nanoctr.cn [National Center for Nanoscience and Technology of China, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety (China)

    2012-08-15

    A novel amphiphilic copolymer with p-maleimidophenyl isocyanate-hydroxypropyl-{beta}-cyclodextrin-polylactide-1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine to generate copolymer nanoparticles (NPs) has been designed. In order to develop an active targeting system, integrin {alpha}{sub v}{beta}{sub 3}-specific targeting peptide cyclo(Arg-Gly-Asp-D-Phe-Cys), cRGD, was conjugated to the surface of NPs (NPs-RGD). These NPs were used to encapsulate anti-tumor drug, paclitaxel. The resulting NPs exhibited high drug-loading capacity and controlled drug release in vitro at acidic pH. In vitro cytotoxicity assay demonstrates that paclitaxel-loaded NPs-RGD significantly inhibited B16 tumor cell (high {alpha}{sub v}{beta}{sub 3}) proliferation relative to free paclitaxel and paclitaxel-loaded NPs at high concentrations. Paclitaxel-loaded NPs-RGD localized mainly in lysosomes in B16 cells as revealed by confocal microscopy. These results suggest a novel strategy for fabrication-functionalizing hydroxypropyl-{beta}-cyclodextrin copolymer nanoparticles for targeting delivery of paclitaxel to integrin {alpha}{sub v}{beta}{sub 3}-rich tumor cells. These nanocarriers can be readily extended to couple other bioactive molecules for active targeting and delivery of various chemotherapeutic drugs.

  15. A simple reduction-sensitive micelles co-delivery of paclitaxel and dasatinib to overcome tumor multidrug resistance

    Directory of Open Access Journals (Sweden)

    Li J

    2017-11-01

    Full Text Available Jun Li,1,* Ruitong Xu,2,* Xiao Lu,3 Jing He,1 Shidai Jin1 1Department of Medical Oncology, 2Department of General Practice, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 3Department of Medical Oncology, Changshu No 1 People’s Hospital, Changshu, People’s Republic of China *These authors contributed equally to this work Abstract: Multidrug resistance (MDR is one of the major obstacles in successful chemotherapy. The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating MDR tumor is a good strategy to overcome MDR. In this work, we prepared the simple redox-responsive micelles based on mPEG-SS-C18 as a co-delivery system to load the paclitaxel (PTX and dasatinib (DAS for treatment of MCF-7/ADR cells. The co-loaded micelles had a good dispersity and a spherical shape with a uniform size distribution, and they could quickly disassemble and rapidly release drugs under the reduction environment. Compared with MCF-7 cells, the DAS and PTX co-loaded redox-sensitive micelle (SS-PDNPs showed stronger cytotoxicity and a more improving intracellular drug concentration than other drug formulations in MCF-7/ADR cells. In summary, the results suggested that the simple co-delivery micelles of PTX and DAS possessed significant potential to overcome drug resistance in cancer therapy. Keywords: redox responsive, overcoming multidrug resistant, co-delivery, paclitaxel, dasatinib 

  16. Rethinking production of Taxol® (paclitaxel) using endophyte biotechnology.

    Science.gov (United States)

    Kusari, Souvik; Singh, Satpal; Jayabaskaran, Chelliah

    2014-06-01

    Taxol® (generic name paclitaxel) represents one of the most clinically valuable natural products known to mankind in the recent past. More than two decades have elapsed since the notable discovery of the first Taxol®-producing endophytic fungus, which was followed by a plethora of reports on other endophytes possessing similar biosynthetic potential. However, industrial-scale Taxol® production using fungal endophytes, although seemingly promising, has not seen the light of the day. In this opinion article, we embark on the current state of knowledge on Taxol® biosynthesis focusing on the chemical ecology of its producers, and ask whether it is actually possible to produce Taxol® using endophyte biotechnology. The key problems that have prevented the exploitation of potent endophytic fungi by industrial bioprocesses for sustained production of Taxol® are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Dendritic polyglycerol sulfate as a novel platform for paclitaxel delivery: pitfalls of ester linkage

    Science.gov (United States)

    Sousa-Herves, Ana; Würfel, Patrick; Wegner, Nicole; Khandare, Jayant; Licha, Kai; Haag, Rainer; Welker, Pia; Calderón, Marcelo

    2015-02-01

    In this study, dendritic polyglycerol sulfate (dPGS) is evaluated as a delivery platform for the anticancer, tubulin-binding drug paclitaxel (PTX). The conjugation of PTX to dPGS is conducted via a labile ester linkage. A non-sulfated dendritic polyglycerol (dPG) is used as a control, and the labeling with an indocarbocyanine dye (ICC) renders multifunctional conjugates that can be monitored by fluorescence microscopy. The conjugates are characterized by 1H NMR, UV-vis measurements, and RP-HPLC. In vitro cytotoxicity of PTX and dendritic conjugates is evaluated using A549 and A431 cell lines, showing a reduced cytotoxic efficacy of the conjugates compared to PTX. The study of uptake kinetics reveals a linear, non saturable uptake in tumor cells for dPGS-PTX-ICC, while dPG-PTX-ICC is hardly taken up. Despite the marginal uptake of dPG-PTX-ICC, it prompts tubulin polymerization to a comparable extent as PTX. These observations suggest a fast ester hydrolysis and premature drug release, as confirmed by HPLC measurements in the presence of plasma enzymes.In this study, dendritic polyglycerol sulfate (dPGS) is evaluated as a delivery platform for the anticancer, tubulin-binding drug paclitaxel (PTX). The conjugation of PTX to dPGS is conducted via a labile ester linkage. A non-sulfated dendritic polyglycerol (dPG) is used as a control, and the labeling with an indocarbocyanine dye (ICC) renders multifunctional conjugates that can be monitored by fluorescence microscopy. The conjugates are characterized by 1H NMR, UV-vis measurements, and RP-HPLC. In vitro cytotoxicity of PTX and dendritic conjugates is evaluated using A549 and A431 cell lines, showing a reduced cytotoxic efficacy of the conjugates compared to PTX. The study of uptake kinetics reveals a linear, non saturable uptake in tumor cells for dPGS-PTX-ICC, while dPG-PTX-ICC is hardly taken up. Despite the marginal uptake of dPG-PTX-ICC, it prompts tubulin polymerization to a comparable extent as PTX. These

  18. Cannabidiol Prevents the Development of Cold and Mechanical Allodynia in Paclitaxel-Treated Female C57Bl6 Mice

    OpenAIRE

    Ward, Sara Jane; Ramirez, Michael David; Neelakantan, Harshini; Walker, Ellen Ann

    2011-01-01

    The taxane chemotherapeutic paclitaxel frequently produces peripheral neuropathy in humans. Rodent models to investigate mechanisms and treatments are largely restricted to male rats, whereas female mouse studies are lacking. We characterized a range of paclitaxel doses on cold and mechanical allodynia in male and female C57Bl/6 mice. Because the nonpsycho-active phytocannabinoid cannabidiol attenuates other forms of neuropathic pain, we assessed its effect on paclitaxel-induced allodynia. Pa...

  19. Targeted sequencing reveals low-frequency variants in EPHA genes as markers of paclitaxel-induced peripheral neuropathy.

    OpenAIRE

    Apellániz-Ruiz, Maria; Tejero, Héctor; Inglada-Pérez, Lucía; Sánchez-Barroso, Lara; Gutiérrez-Gutiérrez, Gerardo; Calvo, Isabel; Castelo, Beatriz; Redondo, Andrés; García-Donás, Jesus; Romero-Laorden, Nuria; Sereno, Maria; Merino, María; Currás-Freixes, Maria; Montero-Conde, Cristina; Mancikova, Veronika

    2017-01-01

    PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes. EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes invo...

  20. A multicenter randomized controlled trial comparing pancreatic leaks after TissueLink versus SEAMGUARD after distal pancreatectomy (PLATS) NCT01051856.

    Science.gov (United States)

    Shubert, Christopher R; Ferrone, Christina R; Fernandez-Del Castillo, Carlos; Kendrick, Michael L; Farnell, Michael B; Smoot, Rory L; Truty, Mark J; Que, Florencia G

    2016-11-01

    Pancreatic leak is common after distal pancreatectomy. This trial sought to compare TissueLink closure of the pancreatic stump to that of SEAMGUARD. A multicenter, prospective, trial of patients undergoing distal pancreatectomy randomized to either TissueLink or SEAMGUARD. Enrollment was closed early due to poor accrual. Overall, 67 patients were enrolled, 35 TissueLink and 32 SEAMGUARD. The two groups differed in American Society of Anesthesiologist class and diagnosis at baseline and were relatively balanced otherwise. Overall, 37 of 67 patients (55%) experienced a leak of any grade, 15 (46.9%) in the SEAMGUARD arm and 22 (62.9%) in the TissueLink arm (P = 0.19). The clinically significant leak rate was 17.9%; 22.9% for TissueLink and 12.5% for SEAMGUARD (P = 0.35). There were no statistically significant differences in major or any pancreatic fistula-related morbidity between the two groups. This is the first multicentered randomized trial evaluating leak rate after distal pancreatectomy between two common transection methods. Although a difference in leak rates was observed, it was not statistically significant and therefore does not provide evidence of the superiority of one technique over the other. Choice should remain based on surgeon comfort, experience, and pancreas characteristics. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Efficacy of electroacupuncture compared with transcutaneous electric nerve stimulation for functional constipation: Study protocol for a randomized, controlled trial.

    Science.gov (United States)

    Zeng, Yuxiao; Zhang, Xuecheng; Zhou, Jing; Wang, Xinwei; Jiao, Ruimin; Liu, Zhishun

    2018-05-01

    To treat functional constipation, both electroacupuncture (EA) therapy and transcutaneous electric nerve stimulation (TENS) are safe and effective. However, no head-to-head comparison trial has been conducted. This trial compares the efficacy of electroacupuncture relative to transcutaneous electric nerve stimulation for functional constipation. Individuals with functional constipation will be randomly allocated to receive either EA or TENS (n = 51, each), 3 times per week for 8 weeks. The primary outcome is the percentage of participants with an average increase from baseline of 1 or more complete spontaneous bowel movements at week 8. The secondary outcome measures are the following: at the time of visits, changes in the number of complete spontaneous bowel movements, number of spontaneous bowel movements, stool character, difficulty in defecation, patients' assessment of quality of life regarding constipation (self-report questionnaire), and use of auxiliary defecation methods. The results of this trial should verify whether EA is more efficacious than TENS for relieving symptoms of functional constipation. The major limitation of the study is the lack of blinding of the participants and acupuncturist.

  2. Trials

    Directory of Open Access Journals (Sweden)

    Michele Fornaro

    2010-01-01

    Full Text Available Mental Retardation (MR is a developmental disability characterized by impairments in adaptive daily life skills and difficulties in social and interpersonal functioning. Since multiple causes may contribute to MR, associated clinical pictures may vary accordingly. Nevertheless, when psychiatric disorders as Treatment Resistant Depression (TRD and/or alcohol abuse co-exist, their proper detection and management is often troublesome, essentially due to a limited vocabulary MR people could use to describe their symptoms, feelings and concerns, and the lack of reliable screening tools. Furthermore, MR people are among the most medicated subjects, with (over prescription of antidepressants and/or typical antipsychotics being the rule rather than exception. Thus, treatment resistance or even worsening of depression, constitute frequent occurrences. This report describes the case of a person with MR who failed to respond to repetitive trials of antidepressant monotherapies, finally recovering using aripiprazole to fluvoxamine augmentation upon consideration of a putative bipolar diathesis for “agitated” TRD. Although further controlled investigations are needed to assess a putative bipolar diathesis in some cases of MR associated to TRD, prudence is advised in the long-term prescription of antidepressant monotherapies in such conditions.

  3. Differential response of immunohistochemically defined breast cancer subtypes to anthracycline-based adjuvant chemotherapy with or without paclitaxel.

    Directory of Open Access Journals (Sweden)

    George Fountzilas

    Full Text Available BACKGROUND: The aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry (IHC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor (ER, progesterone receptor (PgR, HER2, Ki67, cytokeratin 5 (CK5, and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67(low; luminal B (ER/PgR-positive, HER2-negative, Ki67(high; luminal-HER2 (ER/PgR-positive, HER2-positive; HER2-enriched (ER-negative, PgR-negative, HER2-positive; triple-negative (TNBC (ER-negative, PgR-negative, HER2-negative; and basal core phenotype (BCP (TNBC, CK5-positive and/or EGFR-positive. RESULTS: After a median follow-up time of 105.4 months the 5-year disease-free survival (DFS and overall survival (OS rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS (log-rank test; p = 0.021 and p = 0.006, respectively for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 (95% CI: 1.31-2.80, Wald's p = 0.001 and for death 2.53 (95% CI: 1.62-3.60, p<0.001. Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2-enriched tumors

  4. Randomized, double-blinded, placebo-controlled trial comparing two multimodal opioid-minimizing pain management regimens following transsphenoidal surgery.

    Science.gov (United States)

    Shepherd, Deborah M; Jahnke, Heidi; White, William L; Little, Andrew S

    2018-02-01

    OBJECTIVE Pain control is an important clinical consideration and quality-of-care metric. No studies have examined postoperative pain control following transsphenoidal surgery for pituitary lesions. The study goals were to 1) report postoperative pain scores following transsphenoidal surgery, 2) determine if multimodal opioid-minimizing pain regimens yielded satisfactory postoperative pain control, and 3) determine if intravenous (IV) ibuprofen improved postoperative pain scores and reduced opioid use compared with placebo. METHODS This study was a single-center, randomized, double-blinded, placebo-controlled intervention trial involving adult patients with planned transsphenoidal surgery for pituitary tumors randomized into 2 groups. Group 1 patients were treated with scheduled IV ibuprofen, scheduled oral acetaminophen, and rescue opioids. Group 2 patients were treated with IV placebo, scheduled oral acetaminophen, and rescue opioids. The primary end point was patient pain scores (visual analog scale [VAS], rated 0-10) for 48 hours after surgery. The secondary end point was opioid use as estimated by oral morphine equivalents (OMEs). RESULTS Of 136 patients screened, 62 were enrolled (28 in Group 1, 34 in Group 2). The study was terminated early because the primary and secondary end points were reached. Baseline characteristics between groups were well matched except for age (Group 1, 59.3 ± 14.4 years; Group 2, 49.8 ± 16.2 years; p = 0.02). Mean VAS pain scores were significantly different, with a 43% reduction in Group 1 (1.7 ± 2.2) compared with Group 2 (3.0 ± 2.8; p transsphenoidal surgery. IV ibuprofen resulted in significantly improved pain scores and significantly decreased opioid use compared with placebo. Postoperative multimodal pain management, including a nonsteroidal antiinflammatory medication, should be considered after surgery to improve patient comfort and to limit opioid use. Clinical trial registration no.: NCT02351700 (clinicaltrials

  5. Focus on Function – a randomized controlled trial comparing two rehabilitation interventions for young children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Russell Dianne

    2007-09-01

    Full Text Available Abstract Background Children with cerebral palsy receive a variety of long-term physical and occupational therapy interventions to facilitate development and to enhance functional independence in movement, self-care, play, school activities and leisure. Considerable human and financial resources are directed at the "intervention" of the problems of cerebral palsy, although the available evidence supporting current interventions is inconclusive. A considerable degree of uncertainty remains about the appropriate therapeutic approaches to manage the habilitation of children with cerebral palsy. The primary objective of this project is to conduct a multi-site randomized clinical trial to evaluate the efficacy of a task/context-focused approach compared to a child-focused remediation approach in improving performance of functional tasks and mobility, increasing participation in everyday activities, and improving quality of life in children 12 months to 5 years of age who have cerebral palsy. Method/Design A multi-centred randomized controlled trial research design will be used. Children will be recruited from a representative sample of children attending publicly-funded regional children's rehabilitation centers serving children with disabilities in Ontario and Alberta in Canada. Target sample size is 220 children with cerebral palsy aged 12 months to 5 years at recruitment date. Therapists are randomly assigned to deliver either a context-focused approach or a child-focused approach. Children follow their therapist into their treatment arm. Outcomes will be evaluated at baseline, after 6 months of treatment and at a 3-month follow-up period. Outcomes represent the components of the International Classification of Functioning, Disability and Health, including body function and structure (range of motion, activities (performance of functional tasks, motor function, participation (involvement in formal and informal activities, and environment (parent

  6. Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Morris, David E; Lee, Carrie B; Moore, Dominic T; Hayes, D Neil; Halle, Jan S; Rivera, M Patricia; Rosenman, Julian G; Socinski, Mark A

    2008-03-01

    Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT). Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy. Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% > or =5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20 months), respectively. Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing.

  7. Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer

    DEFF Research Database (Denmark)

    Bergmann, Troels K; Gréen, Henrik; Andersen, Charlotte Brasch

    2011-01-01

    Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia, but the interindiv......Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia...

  8. Rationalization of paclitaxel insensitivity of yeast β-tubulin and human βIII-tubulin isotype using principal component analysis

    Directory of Open Access Journals (Sweden)

    Das Lalita

    2012-08-01

    Full Text Available Abstract Background The chemotherapeutic agent paclitaxel arrests cell division by binding to the hetero-dimeric protein tubulin. Subtle differences in tubulin sequences, across eukaryotes and among β-tubulin isotypes, can have profound impact on paclitaxel-tubulin binding. To capture the experimentally observed paclitaxel-resistance of human βIII tubulin isotype and yeast β-tubulin, within a common theoretical framework, we have performed structural principal component analyses of β-tubulin sequences across eukaryotes. Results The paclitaxel-resistance of human βIII tubulin isotype and yeast β-tubulin uniquely mapped on to the lowest two principal components, defining the paclitaxel-binding site residues of β-tubulin. The molecular mechanisms behind paclitaxel-resistance, mediated through key residues, were identified from structural consequences of characteristic mutations that confer paclitaxel-resistance. Specifically, Ala277 in βIII isotype was shown to be crucial for paclitaxel-resistance. Conclusions The present analysis captures the origin of two apparently unrelated events, paclitaxel-insensitivity of yeast tubulin and human βIII tubulin isotype, through two common collective sequence vectors.

  9. A randomized single blind crossover trial comparing leather and commercial wrist splints for treating chronic wrist pain in adults

    Science.gov (United States)

    Thiele, Jill; Nimmo, Rachel; Rowell, Wendy; Quinn, Stephen; Jones, Graeme

    2009-01-01

    Background To compare the effectiveness of a custom-made leather wrist splint (LS) with a commercially available fabric splint (FS) in adults with chronic wrist pain. Methods Participants (N = 25, mean age = 54) were randomly assigned to treatment order in a 2-phase crossover trial. Splints were worn for 2 weeks, separated by a one-week washout period. Outcomes were assessed at baseline and after each splint phase using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Canadian Occupational Performance Measure (COPM) and Jamar dynamometer by an observer blinded to treatment allocation. Results Both styles of wrist splint significantly reduced pain (effect size LS 0.79, FS 0.43), improved hand function and increased grip strength compared to baseline (all p leather splint compared to the commercially available splint. Conclusion Leather wrist splints were superior to a commercially available fabric splint for the short-term relief of pain and dysfunction. PMID:19843345

  10. Report of a randomized trial of d(15)+Be neutrons compared with megavoltage X ray therapy of bladder cancer

    International Nuclear Information System (INIS)

    Duncan, W.; Arnott, S.J.; Jack, W.J.; MacDougall, R.H.; Quilty, P.M.; Rodger, A.; Kerr, G.R.; Williams, J.R.

    1985-01-01

    The results of a randomized trial of d(15)+Be neutrons compared with 4 or 6 MV photons for the treatment of transitional cell carcinoma of the bladder. Between December 1978 and December 1981, 113 patients were accrued, 53 allocated to be treated by neutrons and 60 by photons. Complete local tumor regression was observed in 64% of patients treated by neutrons and 62% treated by photons. Recurrent cancer was subsequently confirmed in 31% of patients, similar in both treatment groups. There was no significant difference in the control rates by T stage between the two treatment groups. Late morbidity was significantly worse in patients treated by neutrons. Following neutron therapy, 78% of patients had serious late morbidity in at least one tissue compared with 38% in the group treated by photons. Survival was significantly better in the photon treated group 45.3% (+/- 11%) at 5 years compared with 12% (+/- 6%) after neutron therapy

  11. Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial

    DEFF Research Database (Denmark)

    Metzger Filho, Otto; Giobbie-Hurder, Anita; Mallon, Elizabeth

    2015-01-01

    assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity......PURPOSE: To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma. PATIENTS AND METHODS: Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly...

  12. At what price? A cost-effectiveness analysis comparing trial of labour after previous Caesarean versus elective repeat Caesarean delivery.

    LENUS (Irish Health Repository)

    Fawsitt, Christopher G

    2013-01-01

    Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland.

  13. A Randomized, Controlled Trial of Meditation Compared to Exposure Therapy and Education Control on PTSD in Veterans

    Science.gov (United States)

    2015-10-01

    score >45. Exclusion criteria: Service related trauma within last 3 months, history of schizophrenia, bipolar disorder , dementia, moderate or severe...7.7% 0.0% 8.3% 0.191 Bipolar disorder , % 7.7% 10.3% 13.9% 0.681 Substance use disorder , % 30.8% 43.6% 41.7% 0.458 Major depressive disorder ...Award Number: W81XWH-12-1-0576 TITLE: A Randomized, Controlled Trial of Meditation Compared to Exposure Therapy and Education Control on PTSD in

  14. A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D.

    Science.gov (United States)

    Eswaran, Shanti L; Chey, William D; Han-Markey, Theresa; Ball, Sarah; Jackson, Kenya

    2016-12-01

    There has been an increasing interest in the role of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) in irritable bowel syndrome (IBS). We report results from the first randomized controlled trial of the low FODMAP diet in US adults with IBS and diarrhea (IBS-D). The objectives were to compare the efficacy of the low FODMAP diet vs. a diet based upon modified National Institute for Health and Care Excellence guidelines (mNICE) on overall and individual symptoms in IBS-D patients. This was a single-center, randomized-controlled trial of adult patients with IBS-D (Rome III) which compared 2 diet interventions. After a 2-week screening period, eligible patients were randomized to a low FODMAP or mNICE diet for 4 weeks. The primary end point was the proportion of patients reporting adequate relief of IBS-D symptoms ≥50% of intervention weeks 3-4. Secondary outcomes included a composite end point which required response in both abdominal pain (≥30% reduction in mean daily pain score compared with baseline) and stool consistency (decrease in mean daily Bristol Stool Form of ≥1 compared with baseline), abdominal pain and stool consistency responders, and other key individual IBS symptoms assessed using daily questionnaires. After screening, 92 subjects (65 women, median age 42.6 years) were randomized. Eighty-four patients completed the study (45 low FODMAP, 39 mNICE). Baseline dem