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Sample records for adjuvant tamoxifen therapy

  1. Virginal Breast Hypertrophy: Different Presentations of 2 Cases and the Role of Tamoxifen as an Adjuvant Therapy.

    Science.gov (United States)

    Karagüzel, Gülay; Bilen, Sevcan; Karaçal, Naci; Yıldız, Kadriye; Livaoğlu, Murat

    2016-10-01

    Virginal breast hypertrophy is a rapid and massive enlargement of one or both breasts. There are several proposed causes and treatment options for virginal breast hypertrophy, but the investigations to support these theories are lacking. We report two premenarchal girls with virginal breast hypertrophy who presented as different clinical cases. After their surgical interventions, their clinical courses were followed for more than 2 years with tamoxifen as an adjuvant therapy. Breast size and shape disorders can be a disturbing cosmetic problem for adolescents who worry about their body image. A combination treatment of breast reduction surgery and tamoxifen is reasonable and can eliminate the need for repeated surgeries for girls with virginal breast hypertrophy. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  2. Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer

    International Nuclear Information System (INIS)

    Andersson, M.; Storm, H.H.; Mouridsen, H.T.

    1991-01-01

    The incidence of new primary cancers was evaluated in 3538 postmenopausal patients who had received surgical treatment for primary breast cancer. Of these patients, 1828 with a low risk of recurrence received no further treatment. High-risk patients were randomly assigned to one of two groups. The first group (n = 846) received postoperative radiotherapy, while the second group (n = 864) received radiotherapy plus tamoxifen at a dose of 30 mg given daily for 48 weeks. The median observation time was 7.9 years. In comparison with the number of new cancers in the general population, the number of new cancers in the three groups was elevated mostly due to a high number of cancers of the contralateral breast and of colorectal cancers in the high-risk groups. The cumulative risk of nonlymphatic leukemia was increased among patients who received postoperative radiotherapy (P = .04). Cancer incidence in the high-risk tamoxifen-treated group relative to that in the high-risk group not treated with tamoxifen was not significant (1.3). No protective effect of tamoxifen on the opposite breast was seen (rate ratio for breast cancer = 1.1), but a tendency to an elevated risk of endometrial cancer was observed (rate ratio = 3.3; 95% confidence interval = 0.6-32.4). Continued and careful follow-up of women treated with tamoxifen is necessary to clarify the potential cancer-suppressive or cancer-promoting effects of this drug

  3. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer

    DEFF Research Database (Denmark)

    Jensen, Maj-Britt; Krarup, Jens Fabricius; Palshof, Torben

    2018-01-01

    randomly assigned to two years of daily placebo or tamoxifen. Survival statistics was collected from the Danish Civil Registration System. RESULTS: The five-year invasive breast cancer recurrence (BCR) rate was 43.2% in the placebo arm and 31.9% in the tamoxifen arm. Compared with the placebo arm...... the hazard ratio for a BCR event was 0.73 in the tamoxifen arm (p = .07). With an estimated median follow-up on overall survival of 40.9 years, 154 and 145 patients had died in the placebo and tamoxifen arm, respectively. After adjustment for baseline characteristics a significant reduction in mortality...

  4. Tamoxifen therapy in breast cancer control worldwide.

    OpenAIRE

    Love, R. R.; Koroltchouk, V.

    1993-01-01

    In most developed and many developing countries, breast cancer is the most frequent cancer and the leading cause of cancer death among women. At least 50% of all breast cancer patients worldwide would survive longer, however, if public awareness about and early detection of the condition were increased and greater use were made of efficient treatment of proven value. With early-stage, localized breast cancer, local treatment combined with adjuvant hormonal therapy with tamoxifen, a synthetic ...

  5. Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

    Science.gov (United States)

    Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

    2009-06-01

    Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years

  6. Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1-98 trial

    DEFF Research Database (Denmark)

    Ewertz, Marianne; Gray, Kathryn P; Regan, Meredith M

    2012-01-01

    To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up....

  7. Excellent outcomes with adjuvant toremifene or tamoxifen in early stage breast cancer

    Directory of Open Access Journals (Sweden)

    Jaime D. Lewis

    2014-01-01

    Full Text Available Fareston (toremifene and tamoxifen, both selective estrogen receptor modulators, are therapeutically equivalent treatments for metastatic breast cancer. We hypothesized that toremifene as compared with tamoxifen given as adjuvant therapy for early stage breast cancer would result in equivalent survival with an improved side effect profile, therefore, providing superior therapeutic efficacy.Subjects and methods. The North American Fareston versus Tamoxifen Adjuvant trial assigned 1813 perimenopausal or postmenopausal women with hormone receptor (HR – positive invasive breast cancer to adjuvant treatment with either tamoxifen or toremifene. The primary outcomes evaluated were disease-free survival (DFS and overall survival (OS.Results. Median follow-up was 59 months. The baseline characteristics of the 2 treatment groups were well-balanced. On the basis of intenttotreat, 5-year actuarial DFS was not significantly different between tamoxifen and toremifene (91.2 % (standard error of the mean (SE 1.2 % vs 91.2 % (SE 1.1 %, respectively. Similarly, 5-year actuarial OS was not significantly different between tamoxifen and toremifene (92.7 % (SE 1.1 % vs 93.7 % (SE 1.0 %, respectively. Controlling for patient age, tumor size, and tumor grade, a Cox multivariate survival analysis found no difference between patients randomized to toremifene versus tamoxifen in terms of OS (OR 0.951; 95 % confidence interval (CI, 0.623–1.451, p = 0.951 or DFS (OR 1.037; 95 % CI, 0.721–1.491, p = 0.846. Adverse events were similar in the 2 groups.Conclusions. Women treated with adjuvant hormonal therapy enjoyed excellent DFS and OS. No significant differences were found between treatment with either tamoxifen or toremifene. Treatment of HR-positive patients with either tamoxifen or toremifene is appropriate.

  8. Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in a randomized trial comparing adjuvant letrozole and tamoxifen therapy in postmenopausal breast cancer

    DEFF Research Database (Denmark)

    Alkner, S; Jensen, M-B; Rasmussen, B B

    2017-01-01

    PURPOSE: To evaluate the estrogen receptor coactivator amplified in breast cancer 1 (AIB1) as a prognostic marker, as well as a predictive marker for response to adjuvant tamoxifen and/or aromatase inhibitors, in early estrogen receptor-positive breast cancer. METHOD: AIB1 was analyzed...... with immunohistochemistry in tissue microarrays of the Danish subcohort (N = 1396) of the International Breast Cancer Study Group's trial BIG 1-98 (randomization between adjuvant tamoxifen versus letrozole versus the sequence of the two drugs). RESULTS: Forty-six percent of the tumors had a high AIB1 expression. In line...... with previous studies, AIB1 correlated to a more aggressive tumor-phenotype (HER2 amplification and a high malignancy grade). High AIB1 also correlated to higher estrogen receptor expression (80-100 vs. 1-79%), and ductal histological type. High AIB1 expression was associated with a poor disease-free survival...

  9. Meta-analysis of trials comparing anastrozole and tamoxifen for adjuvant treatment of postmenopausal women with early breast cancer

    Directory of Open Access Journals (Sweden)

    Tas Faruk

    2008-07-01

    Full Text Available Abstract Objective It was aimed to review the literature and make a meta-analysis of the trials on both upfront, switching, and sequencing anastrozole in the adjuvant treatment of early breast cancer. Methods The PubMed, ClinicalTrials.gov and Cochrane databases were systematically reviewed for randomized-controlled trials comparing anastrozole with tamoxifen in the adjuvant treatment of early breast cancer. Results The combined hazard rate of 4 trials for event-free survival (EFS was 0.77 (95%CI: 0.70–0.85 (P P P Conclusion Anastrozole appears to have superior efficacy than tamoxifen in the adjuvant hormonal treatment of early breast cancer. Until further clinical evidence comes up, aromatase inhibitors should be the initial hormonal therapy in postmenopausal early breast cancer patients and switching should only be considered for patients who are currently receiving tamoxifen.

  10. Ovarian hyperstimulation syndrome followed by ovarian torsion in premenopausal patient using adjuvant tamoxifen treatment for breast cancer

    Directory of Open Access Journals (Sweden)

    Behnaz Moradi

    2016-09-01

    Full Text Available Tamoxifen is a popular medication used in the adjuvant therapy of hormone sensitive breast cancer. In this case report we describe a 39 years old woman presented with ovarian hyperstimulation on the underlying thamoxifen treatment and consecutive ovarian torsion.

  11. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer: long-term follow-up of the Copenhagen breast cancer trial.

    Science.gov (United States)

    Jensen, Maj-Britt; Krarup, Jens Fabricius; Palshof, Torben; Mouridsen, Henning T; Ejlertsen, Bent

    2018-01-01

    The Copenhagen Breast Cancer Trial (CBCT) randomly assigned patients with early breast cancer to two years of tamoxifen or placebo and we evaluated the effect over the following four decades. Between 1975 and 1978, 327 patients with primary breast cancer were randomly assigned to two years of daily placebo or tamoxifen. Survival statistics was collected from the Danish Civil Registration System. The five-year invasive breast cancer recurrence (BCR) rate was 43.2% in the placebo arm and 31.9% in the tamoxifen arm. Compared with the placebo arm the hazard ratio for a BCR event was 0.73 in the tamoxifen arm (p = .07). With an estimated median follow-up on overall survival of 40.9 years, 154 and 145 patients had died in the placebo and tamoxifen arm, respectively. After adjustment for baseline characteristics a significant reduction in mortality was obtained from tamoxifen (HR 0.79; p = .04). Two years of adjuvant tamoxifen resulted in a sustained reduction in mortality in pre- and postmenopausal high-risk breast cancer patients with long-term follow-up data.

  12. Quality of life in relation to tamoxifen or exemestane treatment in postmenopausal breast cancer patients: a Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial side study

    NARCIS (Netherlands)

    van Nes, J. G. H.; Fontein, D. B. Y.; Hille, E. T. M.; Voskuil, D. W.; van Leeuwen, F. E.; de Haes, J. C. J. M.; Putter, H.; Seynaeve, C.; Nortier, J. W. R.; van de Velde, C. J. H.

    2012-01-01

    Tamoxifen and aromatase inhibitors are associated with side effects which can significantly impact quality of life (QoL). We assessed QoL in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial and compared these data with reported adverse events in the main database. 2,754 Dutch

  13. Quality of life in relation to tamoxifen or exemestane treatment in postmenopausal breast cancer patients : a Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial side study

    NARCIS (Netherlands)

    van Nes, J. G. H.; Fontein, D. B. Y.; Hille, E. T. M.; Voskuil, D. W.; van Leeuwen, F. E.; de Haes, J. C. J. M.; Putter, H.; Seynaeve, C.; Nortier, J. W. R.; van de Velde, C. J. H.

    Tamoxifen and aromatase inhibitors are associated with side effects which can significantly impact quality of life (QoL). We assessed QoL in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial and compared these data with reported adverse events in the main database. 2,754 Dutch

  14. Principles of management of recurrence of breast cancer after tamoxifen therapy (abstract)

    International Nuclear Information System (INIS)

    Rasool, I.

    1999-01-01

    The management of recurrence of breast cancer after Tamoxifen therapy needs special attention. The recurrence can be local or distant. The patient, should be thoroughly investigated to find out exact sites of recurrences. Local recurrence is managed by excision, skin grafting or various types of flaps. If extensive radiation is administrated or if not given previously. The distant recurrence in patients who have had adjuvant menopausal status, sites of recurrence while life threatening or not and previous response. The patients who are post menopausal have responded to previous Tamoxifen therapy, long DFI and soft tissues and bony metastasis are best managed by Aromatase inhibitors i.e. Letrozole. (author)

  15. Role of Ki67 in predicting resistance to adjuvant tamoxifen in postmenopausal breast cancer patients.

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    Elzawahry, Heba M; Saber, Magdy M; Mokhtar, Nadia M; Zeeneldin, Ahmed A; Ismail, Yahia M; Alieldin, Nelly H

    2013-12-01

    Breast cancer (BC) is a major health problem in Egypt and worldwide. Its prognosis depends not only on tumor stage but also on tumor biology. To correlate the expression of Ki67 with the clinical outcomes of early hormone-receptor positive postmenopausal BC patients who are receiving tamoxifen. This cohort study included 70 patients. They were followed up for a minimum of 2 years. Ki67 was assessed on paraffin-embedded blocks using immunohistochemistry methods. The median Ki67 value was 22.5% (IQR, 10%-50%). Ki67 was significantly higher in patients with HER2 positive tumors compared to HER2 negative tumors. After a median follow up period of 53 months, 22 patients (31%) developed disease recurrence either loco-regional or distant in 5.7% and 30%, respectively. Recurrent patients had significantly higher tumor stage, nodal stage and Ki67 values compared to non-recurrent cases. The 2-, 3- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 100% & 91%, 98% & 84% and 77% & 59%, respectively. DFS was significantly worse with higher TNM stage, lower ER expression and higher Ki67 values. OS was significantly worse in patients with Ki67 values ≥ 30%. Ki67 ≥ 30% was an independent predictor of recurrence, poor DFS and OS. High Ki67 expression is predictive of poor prognosis and of resistance to adjuvant tamoxifen therapy in postmenopausal BC. We recommend considering Ki67 as one of the risk factors that guide adjuvant treatment decisions. Copyright © 2013. Production and hosting by Elsevier B.V.

  16. Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

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    Dominick, Sally; Hickey, Martha; Chin, Jason; Su, H Irene

    2015-12-09

    Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or

  17. Luteininzing hormone releasing hormones analogs in combination with tamoxifen for the adjuvant treatment of premenopausal women with hormone receptor positive breast cancer.

    Science.gov (United States)

    Conte, Benedetta; Poggio, Francesca; Del Mastro, Lucia

    2017-09-01

    The role of ovarian function suppression (OFS) through luteinizing hormone-releasing hormone agonists (LHRHa) in addition to tamoxifen has been questioned until recently. In 2015, two large clinical trials led to a paradigm shift in the adjuvant endocrine treatment of premenopausal women, introducing the use of LHRHa plus tamoxifen (or aromatase inhibitor, AI) into current clinical practice. Areas covered: The present review aims to provide an in-depth overview of the role of LHRHa+tamoxifen for the adjuvant treatment of premenopausal women with hormone receptor positive breast cancer (HR+BC). Expert opinion: The addition of LHRHa to endocrine treatment (either tamoxifen or AI) is effective in premenopausal women who are at high risk of relapse. To date, no clear recommendations are available for the choice between LHRHa+tamoxifen and LHRH+AI. Although recent data showed better DFS with LHRHa+AI, other issues should be considered: 1) approximately 20 out of 100 women do not reach complete OFS with LHRHa+AI; 2) there is no extended endocrine therapy option that can be applied to women who received 5 years of LHRHa+AI and remained premenopausal at the end of the fifth year. Long-term results of the SOFT-TEXT study are needed to establish if LHRHa+AI is superior to LHRHa+tamoxifen.

  18. Tamoxifen

    Science.gov (United States)

    ... their age, personal medical history, and family medical history.Tamoxifen is in a class of medications known as antiestrogens. It blocks the activity of estrogen (a female hormone) in the breast. This may stop the growth ...

  19. Oxidative stress contributes to the tamoxifen-induced killing of breast cancer cells: implications for tamoxifen therapy and resistance.

    Science.gov (United States)

    Bekele, Raie T; Venkatraman, Ganesh; Liu, Rong-Zong; Tang, Xiaoyun; Mi, Si; Benesch, Matthew G K; Mackey, John R; Godbout, Roseline; Curtis, Jonathan M; McMullen, Todd P W; Brindley, David N

    2016-02-17

    Tamoxifen is the accepted therapy for patients with estrogen receptor-α (ERα)-positive breast cancer. However, clinical resistance to tamoxifen, as demonstrated by recurrence or progression on therapy, is frequent and precedes death from metastases. To improve breast cancer treatment it is vital to understand the mechanisms that result in tamoxifen resistance. This study shows that concentrations of tamoxifen and its metabolites, which accumulate in tumors of patients, killed both ERα-positive and ERα-negative breast cancer cells. This depended on oxidative damage and anti-oxidants rescued the cancer cells from tamoxifen-induced apoptosis. Breast cancer cells responded to tamoxifen-induced oxidation by increasing Nrf2 expression and subsequent activation of the anti-oxidant response element (ARE). This increased the transcription of anti-oxidant genes and multidrug resistance transporters. As a result, breast cancer cells are able to destroy or export toxic oxidation products leading to increased survival from tamoxifen-induced oxidative damage. These responses in cancer cells also occur in breast tumors of tamoxifen-treated mice. Additionally, high levels of expression of Nrf2, ABCC1, ABCC3 plus NAD(P)H dehydrogenase quinone-1 in breast tumors of patients at the time of diagnosis were prognostic of poor survival after tamoxifen therapy. Therefore, overcoming tamoxifen-induced activation of the ARE could increase the efficacy of tamoxifen in treating breast cancer.

  20. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.

    Science.gov (United States)

    Coombes, R Charles; Hall, Emma; Gibson, Lorna J; Paridaens, Robert; Jassem, Jacek; Delozier, Thierry; Jones, Stephen E; Alvarez, Isabel; Bertelli, Gianfilippo; Ortmann, Olaf; Coates, Alan S; Bajetta, Emilio; Dodwell, David; Coleman, Robert E; Fallowfield, Lesley J; Mickiewicz, Elizabeth; Andersen, Jorn; Lønning, Per E; Cocconi, Giorgio; Stewart, Alan; Stuart, Nick; Snowdon, Claire F; Carpentieri, Marina; Massimini, Giorgio; Bliss, Judith M; van de Velde, Cornelius

    2004-03-11

    Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor-positive breast cancer. Despite this treatment, however, some patients have a relapse. We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival. Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported--183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04). Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment. Copyright 2004 Massachusetts Medical Society

  1. Adjuvant Tamoxifen Plus Ovarian Function Suppression Versus Tamoxifen Alone in Premenopausal Women With Early Breast Cancer: Patient-Reported Outcomes in the Suppression of Ovarian Function Trial

    Science.gov (United States)

    Luo, Weixiu; Bernhard, Jürg; Francis, Prudence A.; Burstein, Harold J.; Ciruelos, Eva; Bellet, Meritxell; Pavesi, Lorenzo; Lluch, Ana; Visini, Marilena; Parmar, Vani; Tondini, Carlo; Kerbrat, Pierre; Perelló, Antonia; Neven, Patrick; Torres, Roberto; Lombardi, Davide; Puglisi, Fabio; Karlsson, Per; Ruhstaller, Thomas; Colleoni, Marco; Coates, Alan S.; Goldhirsch, Aron; Price, Karen N.; Gelber, Richard D.; Regan, Meredith M.; Fleming, Gini F.

    2016-01-01

    Purpose The Suppression of Ovarian Function trial showed improved disease control for tamoxifen plus ovarian function suppression (OFS) compared with tamoxifen alone for the cohort of premenopausal patients who received prior chemotherapy. We present the patient-reported outcomes. Patients and Methods The quality-of-life (QoL) analysis includes 1,722 of 2,045 premenopausal patients with hormone receptor–positive breast cancer randomly assigned to receive adjuvant treatment with 5 years of tamoxifen plus OFS or tamoxifen alone. Chemotherapy use before enrollment was optional. Patients completed a QoL form consisting of global and symptom indicators at baseline, every 6 months for 24 months, and annually during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6, 24, and 60 months with mixed models for repeated measures with and without chemotherapy and overall. Results Patients on tamoxifen plus OFS were more affected than patients on tamoxifen alone by hot flushes at 6 and 24 months, by loss of sexual interest and sleep disturbance at 6 months, and by vaginal dryness up to 60 months. Without prior chemotherapy, patients on tamoxifen alone reported more vaginal discharge over the 5 years than patients on tamoxifen plus OFS. Symptom-specific treatment differences at 6 months were less pronounced in patients with prior chemotherapy. Changes in global QoL indicators from baseline were small and similar between treatments over the whole treatment period. Conclusion Overall, OFS added to tamoxifen resulted in worse endocrine symptoms and sexual functioning during the first 2 years of treatment, with variable magnitudes of treatment differences. Short-term differences in symptom-specific QoL, treatment burden, and coping effort between treatment groups were less pronounced for patients with prior chemotherapy, the cohort that benefited most from OFS in terms of disease control. PMID:27022111

  2. Adjuvant therapy of prostate cancer

    International Nuclear Information System (INIS)

    Dubinsky, P.

    2009-01-01

    Outcomes of radical prostatectomy (RP) in high risk prostate cancer are suboptimal. Intensification of local therapy as well as early administration of systemic treatment adjuvant to RP is subject of clinical research. Results of randomised studies are presented. Improvement in overall survival has been reported in adjuvant radiotherapy (RT) in pT3 (extracapsular extension and seminal vesicles invasion) or positive resection margin (R1) and in adjuvant androgen deprivation therapy (ADT) in pN+ disease. (author)

  3. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Jensen, Maj-Britt; Elversang, Johanna

    2013-01-01

    We report the long-term results of a randomised trial comparing tamoxifen with tamoxifen plus cyclophosphamide, methotrexate and fluorouracil (CMF) in postmenopausal high-risk breast cancer patients. In addition, we analyse the prognostic and predictive value of centrally assessed subtypes....

  4. A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study

    International Nuclear Information System (INIS)

    Gu, Ran; Long, Meijun; Chen, Kai; Chen, Lili; Xiao, Qiaozhen; Wu, Mei; Song, Erwei; Su, Fengxi; Jia, Weijuan; Zeng, Yunjie; Rao, Nanyan; Hu, Yue; Li, Shunrong; Wu, Jiannan; Jin, Liang; Chen, Lijuan

    2012-01-01

    In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. Toremifene may be a valid and

  5. CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer

    DEFF Research Database (Denmark)

    Regan, Meredith M; Leyland-Jones, Brian; Bouzyk, Mark

    2012-01-01

    Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer. Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. In this study, we investigated...

  6. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer

    DEFF Research Database (Denmark)

    Mouridsen, H.; Giobbie-Hurder, A.; Goldhirsch, A.

    2009-01-01

    with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P=0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole...

  7. Tamoxifen and ovarian function.

    Directory of Open Access Journals (Sweden)

    Martine Berliere

    Full Text Available BACKGROUND: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy. MATERIALS AND METHODS: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II. All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol. Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year. All data were retrospectively evaluated in 2011. RESULTS: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year b: Oligomenorrhea (5 to 9 cycles/year c: Severe oligomenorrhea (1 to 4 cycles/year d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values. CONCLUSIONS: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status

  8. Risk of Parkinson's disease after tamoxifen treatment

    Directory of Open Access Journals (Sweden)

    Destefano Anita L

    2010-04-01

    Full Text Available Abstract Background Women have a reduced risk of developing Parkinson's disease (PD compared with age-matched men. Neuro-protective effects of estrogen potentially explain this difference. Tamoxifen, commonly used in breast cancer treatment, may interfere with the protective effects of estrogen and increase risk of PD. We compared the rate of PD in Danish breast cancer patients treated with tamoxifen to the rate among those not treated with tamoxifen. Methods A cohort of 15,419 breast cancer patients identified from the Danish Breast Cancer Collaborative Group database was linked to the National Registry of Patients to identify PD diagnoses. Overall risk and rate of PD following identification into the study was compared between patients treated with tamoxifen as adjuvant hormonal therapy and patients not receiving tamoxifen. Time-dependent effects of tamoxifen treatment on PD rate were examined to estimate the likely induction period for tamoxifen. Results In total, 35 cases of PD were identified among the 15,419 breast cancer patients. No overall effect of tamoxifen on rate of PD was observed (HR = 1.3, 95% CI: 0.64-2.5, but a PD hazard ratio of 5.1 (95% CI: 1.0-25 was seen four to six years following initiation of tamoxifen treatment. Conclusions These results provide evidence that the neuro-protective properties of estrogen against PD occurrence may be disrupted by tamoxifen therapy. Tamoxifen treatments may be associated with an increased rate of PD; however these effects act after four years, are of limited duration, and the adverse effect is overwhelmed by the protection against breast recurrence conferred by tamoxifen therapy.

  9. Extended Adjuvant Therapy for Breast Cancer

    Science.gov (United States)

    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  10. Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

    DEFF Research Database (Denmark)

    Joshi, Tejal; Elias, Daniel; Stenvang, Jan

    2016-01-01

    Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of mi......+ breast cancer patients receiving adjuvant tamoxifen mono-therapy. Our results provide new insight into the molecular mechanisms of tamoxifen resistance and may form the basis for future medical intervention for the large number of women with tamoxifen-resistant ER+ breast cancer.......RNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all Tam...

  11. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    International Nuclear Information System (INIS)

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-01-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer

  12. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    Science.gov (United States)

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  13. Overview from the International Conference on Long-Term Tamoxifen Therapy for Breast Cancer.

    Science.gov (United States)

    Jordan, V C

    1992-02-19

    The development of tamoxifen therapy to treat selected patients, with all stages of breast cancer, has provided the clinical community with an efficacious and safe drug for long-term therapy. Issues of safety are under constant review, but justified concerns about high doses of tamoxifen acting as a promoter of liver cancer in rats or as a promoter of endometrial cancer in women have not, as yet, proved to be of clinical relevance. The situation will continue to be reviewed during the development of the prevention studies in Europe and the United States because an improvement in women's health is the ultimate goal of these programs. The hallmark for the successful development of tamoxifen has been the close cooperation between the laboratory and the clinic. The clinical strategy of long-term tamoxifen therapy is a direct application of a laboratory concept. Furthermore, potential problems in the clinic have been identified in the laboratory, and the clinical community has responded quickly to evaluate the real risks to the patient population. This close cooperation will continue. Issues of drug resistance, new antiestrogen development, and the application of the knowledge about steroid receptors to develop targeted gene therapies are being addressed so that additional treatment approaches for breast cancer will be in place by the turn of the century.

  14. Synthesis and characterization of Tamoxifen citrate modified reduced graphene oxide nano sheets for breast cancer therapy.

    Science.gov (United States)

    Zhang, Yu-Jin; Li, Bao-An; Li, Zhao-Yuan; Xia, Ning; Yu, Hai-Ying; Zhang, Ya-Zhi

    2018-03-01

    Theranostic agents are of immense consideration in the current generation nanomedicine. In this study, we have developed a facile approach for the fabrication of Tamoxifen citrate modified nanosized reduced graphene oxide (nano-rGO) with more stability and low cytotoxicity. The prepared nano-rGO sheets were characterized using HR-TEM and AFM imaging techniques. Further, the cytotoxicity was assessed using MTT assay on female BALB/c nude mice MCF-7 cell lines. In addition, by means of continuous-wave near-infrared laser, cancer cells in vivo were significantly ablated because of the photothermal effect stimulated by tamoxifen modified nano-rGO. These results indicated that the prepared tamoxifen modified nano-rGO has the ability to apply in the photothermal therapy of breast cancers. Consequently, further exploration of photothermal therapeutics is desirable for the synthesis of novel nano materials with additional functionalities. Copyright © 2017. Published by Elsevier B.V.

  15. Tamoxifen for Breast Cancer

    Directory of Open Access Journals (Sweden)

    A Karn

    2010-03-01

    Full Text Available Breast cancer is one of the common cancers. Hormonal therapy along with surgery, chemotherapy, radiotherapy and targeted therapy are vital modalities for the management of breast cancer. Tamoxifen has been the most widely used hormonal therapy for more than two decades. In this article we review the benefits, dose, duration and timing of Tamoxifen therapy in patients with breast cancer. Keywords: breast cancer, hormonal therapy, tamoxifen.

  16. Synchronous uterine carcinosarcoma and contralateral breast cancer after tamoxifen therapy: a case report.

    Science.gov (United States)

    Shen, Ling; Hong, Liangli; Zhang, Guohong; Mai, Ruiqin

    2014-01-01

    Uterine carcinosarcoma (malignant mixed Müllerian tumor, MMMT) is a rare aggressive malignant tumor, which demonstrates both malignant epithelial (carcinoma) and mesenchymal (sarcoma) components. Synchronous uterine carcinosarcoma and contralateral breast cancer in patient received tamoxifen treatment had not been reported. We present a case of uterine carcinosarcoma co-occurrenced with contralateral breast cancer in a 56-year-old nulliparous, obese breast cancer patient, who had been treated with tamoxifen for 5 years. The patient presented with palpable pelvic mass and vaginal bleeding. Histopathological evidence revealed that the tumor was comprised of an admixture of malignant epithelial and mesenchymal components. The epithelial component was endometrioid type adenocarcinoma, while sarcomatous component had heterologous elements including fusiform cell sarcoma and a prominent component of cartilage. The infiltrating ductal carcinoma has been diagnosed on her right breast. The patient died of disease 8 months after diagnosis. Postmenopausal patients, with adjuvant tamoxifen treatment for breast cancer, are at increased risk for the development of uterine carcinosarcoma and less benefit for contralateral breast cancer.

  17. Postoperative adjuvant therapy of colorectal carcinoma

    International Nuclear Information System (INIS)

    Scheithauer, W.

    1989-01-01

    Evaluating the results of controlled clinical trials, an attempt has been made to summarize the current status of adjuvant therapy in colorectal cancer. Several different adjuvant treatment approaches including immunotherapy, postoperative fibrinolysis, anticoagulation, pre- and postoperative radiotherapy when used as a single modality, have not resulted in any long-term survival benefit. Rather in contrast to previous experiences, recent prospective randomized trials have provided evidence for the efficacy of chemotherapy in the adjuvant treatment of colon and rectal cancer. Whereas its definitive role in the former disease remains somewhat controversial, for rectal cancer, it seems clear that combined modality therapy including polychemotherapy with or without radiation prolongs the disease-free interval, lowers the local recurrence rate, and may improve survival compared to surgery alone. Questions which remain to be answered by future clinical trials are related to the optimal duration and sequence of combined modality, to the role of different radiation sensitizers, and in both colon and rectal cancer, to the choice of the most effective systemtic chemotherapeutic drugs. (orig./MG) [de

  18. Long-term efficacy and safety of letrozole for the adjuvant treatment of early breast cancer in postmenopausal women: a review

    Directory of Open Access Journals (Sweden)

    Alain Monnier

    2009-09-01

    Full Text Available Alain MonnierInstitut Régional Fédératif du Cancer (IFRC, Centre Hospitalier Belfort-Montbéliard, Montbéliard, FranceAbstract: Aromatase inhibitors (AIs are becoming more widely used than tamoxifen as adjuvant hormonal therapy for postmenopausal women (PMW with early breast cancer (EBC. It is clear that these drugs offer important efficacy benefits over tamoxifen and differ from tamoxifen in their safety profile. The accepted strategies for adjuvant AI therapy include initial adjuvant treatment following surgery, switching and/or sequencing from prior tamoxifen, and extended adjuvant therapy following the full 5 years of tamoxifen treatment. Among the available AIs, letrozole has been evaluated in large, well-controlled, double-blind clinical trials in the initial adjuvant, extended adjuvant, and more recently, the sequential adjuvant settings. Letrozole is the most potent of the AIs and provides near complete suppression of plasma estrogens in PMW. Letrozole also significantly reduces the occurrence of early distant metastases, the most lethal type of recurrence event, which can lead to improved survival. Clinical comparisons of letrozole with both tamoxifen and placebo have also provided important long-term safety data on the use of AIs as adjuvant therapy in PMW with EBC. The weight of clinical evidence indicates that letrozole is a safe and effective option for adjuvant hormonal therapy across all three AI treatment settings.Keywords: aromatase inhibitor, breast cancer, hormonal therapy, letrozole, postmenopausal women, tamoxifen

  19. Combination of methylselenocysteine with tamoxifen inhibits MCF-7 breast cancer xenografts in nude mice through elevated apoptosis and reduced angiogenesis.

    Science.gov (United States)

    Li, Zengshan; Carrier, Latonya; Belame, Aditi; Thiyagarajah, Arunthavarani; Salvo, Virgilio A; Burow, Matthew E; Rowan, Brian G

    2009-11-01

    To investigate the therapeutic effect of methylselenocysteine (MSC) combined with tamoxifen in MCF-7 breast cancer xenograft and the underlying mechanisms. MCF-7 breast cancer xenograft was established in ovariectomized female athymic nude mice and treated with tamoxifen and/or MSC. Tumor size was measured twice a week. Immunohistochemistry and TUNEL assays were used to measure ERalpha expression, ERalpha target genes (progesterone receptor (PR) and cyclin D1 expression), Ki-67 index, apoptosis and microvessel density. Combined treatment with tamoxifen and MSC synergistically inhibited tumor growth compared to MSC alone and tamoxifen alone. MSC alone or MSC + tamoxifen significantly reduced ERalpha, PR and cyclin D1, Ki67 index and microvessel density while increasing apoptosis in tumor tissues. These findings demonstrate synergistic growth inhibition of ERalpha positive breast cancer xenografts by combination of tamoxifen with organic selenium compounds. Organic selenium may provide added benefit when combined with tamoxifen in adjuvant therapy or prevention.

  20. Long-term effects on the incidence of second primary cancers in a randomized trial of two and five years of adjuvant tamoxifen.

    Science.gov (United States)

    Rosell, Johan; Nordenskjöld, Bo; Bengtsson, Nils-Olof; Fornander, Tommy; Hatschek, Thomas; Lindman, Henrik; Malmström, Per-Olof; Wallgren, Arne; Stål, Olle; Carstensen, John

    2017-04-01

    Tamoxifen is a well established treatment for breast cancer, but its long-term effects on the incidence of secondary cancers are not fully evaluated. We have studied 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after two years of tamoxifen, and who were randomized to receive totally two or five years of therapy. Compared to patients randomized to two years of tamoxifen the incidence of contralateral breast cancer [hazard ratio (HR) 0.73; 95% CI 0.56-0.96] and of lung cancer (HR 0.45; 95% CI 0.27-0.77), especially squamous cell and small cell lung cancer, were reduced in the five-year group, and similar results were seen when restricting the analysis to the 10-year period after treatment stopped. An increased incidence of endometrial cancer was observed in the five-year group, but the excess risk decreased over time. Further studies of the effects of tamoxifen on the risk of different histological types of lung cancer are needed.

  1. Pierre Robin sequence associated with first trimester fetal tamoxifen exposure.

    Science.gov (United States)

    Berger, Joel C; Clericuzio, Carol L

    2008-08-15

    Tamoxifen is a nonsteroidal antiestrogen used as the current adjuvant endocrine treatment of choice for premenopausal women treated for breast cancer and its potential for causing fetal harm during pregnancy remains inconclusive. While the evidence of tamoxifen's effects on humans in utero is minimal, animal studies have shown evidence of teratogenicity, hence the FDA's class D categorization of the drug. In 1994 Cullins et al. published a case report entitled "Goldenhar's Syndrome Associated with Tamoxifen Given to the Mother During Gestation." At the time of publication, the authors noted that the manufacturer of tamoxifen knew of two cases associated with tamoxifen administration which resulted in congenital craniofacial defects. Cullins' case of Goldenhar syndrome is also a craniofacial disorder and thus represented the third such case. We report on the fourth case of a tamoxifen-associated craniofacial anomaly. The mother became pregnant while undergoing tamoxifen therapy for breast cancer. A child with severe micrognathia and cleft palate was born. It is noteworthy that the two patterns of craniofacial malformations in tamoxifen exposed infants--Goldenhar syndrome in Cullins' et al. case and Pierre Robin sequence reported here--have also both been observed in isotretinoin exposed infants. While a larger spectrum of anomalies is characteristic of retinoic acid embryopathy, the specific craniofacial anomalies include facial asymmetry, microtia, micrognatha and U-shaped cleft of the secondary palate, that is, malformations seen in the two tamoxifen exposed infants. Therefore, it is conceivable that these two agents could produce comparable embryotoxic effects if they function in a like way during embryogenesis. While the majority of tamoxifen exposed infants are normal, the ascertainment of teratogenic effects from tamoxifen will best be determined by data from teratogen registries. Copyright 2008 Wiley-Liss, Inc.

  2. [Novel Adjuvant Therapy for Ocular Melanoma].

    Science.gov (United States)

    Bosch, Jacobus J; Heindl, Ludwig M

    2017-05-01

    Background Malignant melanoma is the most common cancer of the eye in adults that originates either in the intra-ocular uveal tract or extra-ocular conjunctiva. Although the primary tumor can be treated successfully, no effective therapy for both metastatic conjunctival and uveal melanoma currently exits. Tumor-associated lymphangiogenesis and immune cell infiltration play a pivotal role in the development and therapeutic targeting of metastases. Project description Here, we provide an overview of current translational research on lymphangiogenesis and its therapeutic inhibition as well as modulation of immune cell infiltration by passive and active immunotherapy in melanoma of the eye. Specifically, our previous and ongoing work on lymphangiogenesis and immune cells in ocular melanoma within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye" is summarized. Conclusions Translational research on the modulation of tumor-associated lymphangiogenesis and immune cell infiltration could provide novel targets for adjuvant therapy in melanoma of the eye. Georg Thieme Verlag KG Stuttgart · New York.

  3. Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients

    DEFF Research Database (Denmark)

    Lyng, Maria B; Lænkholm, Anne-Vibeke; Tan, Qihua

    2013-01-01

    BACKGROUND: Tamoxifen significantly improves outcome for estrogen receptor-positive (ER+) breast cancer, but the 15-year recurrence rate remains 30%. The aim of this study was to identify gene profiles that accurately predicted the outcome of ER+ breast cancer patients who received adjuvant...... Tamoxifen mono-therapy. METHODOLOGY/PRINCIPAL FINDINGS: Post-menopausal breast cancer patients diagnosed no later than 2002, being ER+ as defined by >1% IHC staining and having a frozen tumor sample with >50% tumor content were included. Tumor samples from 108 patients treated with adjuvant Tamoxifen were...

  4. Evaluation of Tamoxifen and metabolites by LC-MS/MS and HPLC Methods

    OpenAIRE

    Heath, D.D.; Flatt, S.W.; Wu, A.H.B.; Pruitt, M.A.; Rock, C.L.

    2014-01-01

    Epidemiological and laboratory evidence suggests that quantification of serum or plasma levels of tamoxifen and the metabolites of tamoxifen, 4-hydroxy-N-desmethyl-tamoxifen (endoxifen), Z-4-hydroxy-tamoxifen (4HT), N-desmethyl-tamoxifen (ND-tam) is a clinically useful tool in the assessment and monitoring of breast cancer status in patients taking adjuvant tamoxifen. A liquid chromatographic mass spectrometric method (LC-MS/MS) was used to measure the blood levels of tamoxifen and the metabo...

  5. The relative benefits of tamoxifen in older women with T1 early-stage breast cancer treated with breast-conserving surgery and radiation therapy.

    Science.gov (United States)

    Khan, Atif J; Parikh, Rahul R; Neboori, Hanmanth J; Goyal, Sharad; Haffty, Bruce G; Moran, Meena S

    2013-01-01

    Small, hormone receptor-positive breast carcinomas in older women are associated with low local recurrence rates. The relative benefits of adjuvant hormonal therapy remain unclear in elderly women with small, node-negative breast cancer after breast-conserving surgery and adjuvant radiation therapy. From our institutional data base, 224 patients ≥65 years of age with T1N0M0 breast cancer treated with BCS+RT were identified. Of these, 102 patients (45.5%) received tamoxifen (TAM) and 122 patients (54.5%) did not (no-TAM). The median follow-up time was 62.6 months. The 10-year local relapse-free survival (LRFS) was 98% in both the TAM and no-TAM cohorts (p = 0.58); the 10-year DMFS was 83% TAM vs. 89% no-TAM (p = 0.91). There was no difference in 10-year contralateral breast relapse or overall survival (OS) between the two cohorts. In univariate and multivariate analysis, use of TAM was not associated with LRFS, distant metastases-free survival (DMFS), OS, or a reduction in contralateral breast cancers when compared with the no-TAM cohort. In this large cohort of T1N0 elderly breast cancer patients treated with CS+RT, the use of TAM did not appear to decrease ipsilateral breast relapse, contralateral breast relapse, distant metastasis, or OS. © 2013 Wiley Periodicals, Inc.

  6. Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat

    Directory of Open Access Journals (Sweden)

    Goldstein Irwin

    2006-09-01

    Full Text Available Abstract Background Tamoxifen, a selective estrogen receptor modulator with both estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in breast cancer patients. Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat. Methods Female Sprague-Dawley rats were subjected to sham surgery or bilateral ovariectomy. After 2 weeks, sham-operated rats were implanted with subcutaneous osmotic infusion pumps containing vehicle (control or tamoxifen (150 μg/day. Ovariectomized rats were similarly infused with vehicle. After an additional 2 weeks, vaginal blood flow responses to pelvic nerve stimulation were measured by laser Doppler flowmetry and vaginal tissue was collected for histological and biochemical assay. Results Tamoxifen treatment did not change plasma estradiol concentrations relative to control animals, while ovariectomized rats exhibited a 60% decrease in plasma estradiol. Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight. Vaginal blood flow was significantly decreased in tamoxifen-infused rats compared to controls. Similar to ovariectomized animals, estrogen receptor binding was increased and arginase enzyme activity was decreased in tamoxifen-infused rats. However, different from control and ovariectomized animals, the vaginal epithelium in tamoxifen-infused rats appeared highly mucified. Periodic acid-Schiff staining confirmed a greater production of carbohydrate-rich compounds (e.g. mucin, glycogen by the vaginal epithelium of tamoxifen-infused rats. Conclusion The observations suggest that tamoxifen exerts both anti-estrogenic and pro

  7. Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

    International Nuclear Information System (INIS)

    Bièche, Ivan; Girault, Igor; Urbain, Estelle; Tozlu, Sengül; Lidereau, Rosette

    2004-01-01

    Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability. To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. Relevant genes were further investigated in a well-defined cohort of 97 ERα-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. Seven of the 27 genes showed very weak or undetectable expression in both normal and tumoral breast tissues. Among the 20 remaining genes, seven genes (CYP2A6, CYP2B6, FMO5, NAT1, SULT2B1, GSTM3 and ABCC11) showed significantly higher mRNA levels in ERα-positive breast tumors than in normal breast tissue, or showed higher mRNA levels in ERα-positive breast tumors than in ERα-negative breast tumors. In the 97 ERα-positive breast tumor series, most alterations of these seven genes corresponded to upregulations as compared with normal breast tissue, with an incidence ranging from 25% (CYP2A6) to 79% (NAT1). Downregulation was rare. CYP2A6, CYP2B6, FMO5 and NAT1 emerged as new putative ERα-responsive genes in human breast cancer. Relapse-free survival was longer among patients with FMO5-overexpressing tumors or NAT1-overexpressing tumors (P = 0.0066 and P = 0.000052, respectively), but only NAT1 status retained prognostic significance in Cox multivariate regression analysis (P = 0.0013). Taken together, these data point to a role of genes coding for xenobiotic-metabolizing enzymes in breast tumorigenesis, NAT1 being an

  8. Tamoxifen- Induced Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Bandyopadhyay Debabrata

    1997-01-01

    Full Text Available A 38 year old woman developed dermatomyositis after radical mastectomy and tamoxifen therapy for metastatic breast carcinoma. The possibility of the drug as the underlying cause of the connective tissue disease is discussed.

  9. Role of chemoradiotherapy in oesophageal cancer -- adjuvant and neoadjuvant therapy

    NARCIS (Netherlands)

    Gwynne, S.; Wijnhoven, B. P. L.; Hulshof, M.; Bateman, A.

    2014-01-01

    Despite low postoperative mortality rates, the long-term outcomes from surgical-based treatment for oesophageal cancer remain poor. Chemoradiotherapy (CRT), either given before surgical resection as neoadjuvant therapy or after resection as adjuvant therapy, has been postulated to improve these

  10. Adjuvant Biological Therapies in Chronic Leg Ulcers

    Directory of Open Access Journals (Sweden)

    Natalia Burgos-Alonso

    2017-11-01

    Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.

  11. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    International Nuclear Information System (INIS)

    Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

    2006-01-01

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed

  12. Tamoxifen therapy for the management of pubertal gynecomastia: a systematic review

    NARCIS (Netherlands)

    Lapid, Oren; van Wingerden, Jan J.; Perlemuter, Leon

    2013-01-01

    Objective: A systematic review to assess the efficacy of tamoxifen in the management of idiopathic pubertal gynecomastia. Data sources: Searches were conducted using the databases of Medline (search engine PubMed) and Web of Science (R). Study selection: Studies reporting the use of Tamoxifen for

  13. Factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen - results from a prospective, single center, case control study.

    Science.gov (United States)

    Kovac, Mirjana; Kovac, Zeljko; Tomasevic, Zorica; Vucicevic, Slavko; Djordjevic, Valentina; Pruner, Iva; Radojkovic, Dragica

    2015-01-01

    Estimates of the risk ratio of tamoxifen-associated venous thromboembolism (VTE) in breast cancer patients range from 2.4 to 7.1. The occurrence of thrombosis in patients with breast cancer complicates the clinical condition and causes a change of treatment. Our study was conducted in order to investigate the influence of patient-related risk factors for thrombosis development in breast cancer patients whose treatment included adjuvant tamoxifen. The prospective, single center, case control study included 150 breast cancer women, 50 whom developed venous thrombosis during adjuvant tamoxifen and 100 whom did not have thrombosis, as a control group. Patient-related risk factors such as: age, body mass index, previous VTE, varicose veins, concomitant diseases, the presence of prothrombotic mutations (FV Leiden, FII G20210A) and FVIII activity were evaluated in both groups. In respect of prothrombotic mutations, the FV Leiden mutation was present in a higher number of women from the VTE group (10/50 vs 7/100; P=0.020). Additionally, FVIII activity was significantly higher in the VTE group; median (IQR), of 1.79 (0.69) vs 1.45 (0.55); P1.5IU/ml, who were carriers of prothrombotic mutations, an OR of 3.76 (CI 95% 1.276-11.096; P=0.016) was obtained for VTE. The results of our study showed that the factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen. Copyright © 2014. Published by Elsevier B.V.

  14. Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

    DEFF Research Database (Denmark)

    Joshi, Tejal; Elias, Daniel; Stenvang, Jan

    2016-01-01

    and 14-3-3 family genes. Integrating the inferred miRNA-target relationships, we investigated the functional importance of 2 central genes, SNAI2 and FYN, which showed increased expression in TamR cells, while their corresponding regulatory miRNA were downregulated. Using specific chemical inhibitors......+ breast cancer patients receiving adjuvant tamoxifen mono-therapy. Our results provide new insight into the molecular mechanisms of tamoxifen resistance and may form the basis for future medical intervention for the large number of women with tamoxifen-resistant ER+ breast cancer....

  15. Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial.

    Science.gov (United States)

    Higgins, Michaela J; Liedke, Pedro E R; Goss, Paul E

    2013-04-01

    Early hormone-receptor-positive breast cancer is a chronic relapsing disease that can remain clinically silent for many years. The NCIC-CTG MA.17/BIG 1-97 trial randomized disease-free early breast cancer patients who had received five years of adjuvant tamoxifen to either letrozole or placebo and was the first to demonstrate a benefit with extended endocrine therapy. MA.17/BIG 1-97 was stopped at the first interim analysis because disease free survival was strongly prolonged in the letrozole arm. Subsequent subset analyses and longer follow up have shown that this therapy improved survival across all groups, particularly among women with node-positive disease and those that were pre-menopausal at time of study enrolment. The MA.17/BIG 1-97 study should be considered a paradigm for extended adjuvant endocrine therapy in hormone-receptor-positive early breast cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial: advancing the science of recruitment and breast cancer risk assessment in minority communities.

    Science.gov (United States)

    McCaskill-Stevens, Worta; Wilson, John W; Cook, Elise D; Edwards, Cora L; Gibson, Regina V; McElwain, Diane L; Figueroa-Moseley, Colmar D; Paskett, Electra D; Roberson, Noma L; Wickerham, D Lawrence; Wolmark, Norman

    2013-04-01

    One of the first chemoprevention trials conducted in the western hemisphere, the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women. The purpose of this report is to review various patient recruitment efforts the NSABP developed to enhance the participation of racial and ethnic minority women in the Study of Tamoxifen and Raloxifene (STAR) trial and to describe the role that the recruitment process played in the implementation and understanding of breast cancer risk assessment in minority communities. The NSABP STAR trial was a randomized, double-blinded study comparing the use of tamoxifen 20 mg/day to raloxifene 60 mg/day, for a 5-year period, to reduce the risk of developing invasive breast cancer. Eligible postmenopausal women were required to have a 5-year predicted breast cancer risk of 1.66% based on the modified Gail Model. For the current report, eligibility and enrollment data were tabulated by race/ethnicity for women who submitted STAR risk assessment forms (RAFs). A total of 184,460 RAFs were received, 145,550 (78.9%) from white women and 38,910 (21.1%) from minority women. Of the latter group, 21,444 (11.6%) were from African Americans/blacks, 7913 (4.5%) from Hispanics/Latinas, and 9553 (5.2%) from other racial or ethnic groups. The percentages of risk-eligible women among African Americans, Hispanics/Latinas, others, and whites were 14.2%, 23.3%, 13.7%, and 57.4%, respectively. Programs targeting minority enrollment submitted large numbers of RAFs, but the eligibility rates of the women referred from those groups tended to be lower than the rates among women referred outside of those programs. The average number of completed risk assessments increased among minority women over the course of the recruitment period compared to those from whites. We have not

  17. Malignant mixed Mullerian tumour of uterus secondary to tamoxifen therapy for hormone responsive breast cancer.

    Science.gov (United States)

    Gupta, Mayank; Kiruthiga, Kala Gnanasekaran

    2015-06-29

    Tamoxifen is used in the treatment of hormone responsive breast cancer because of its antiestrogenic effect. However, it also has an estrogenic effect on the uterus, thereby increasing the risk of endometrial hyperplasia, endometrial polyp and endometrial neoplasms such as endometrial adenocarcinoma and malignant mixed Mullerian tumour (MMMT). This case describes the possible pathogenesis and risk of developing MMMT due to long-term tamoxifen intake in hormone responsive breast cancer. 2015 BMJ Publishing Group Ltd.

  18. Two Years of Adjuvant Tamoxifen Provides a Survival Benefit Compared With No Systemic Treatment in Premenopausal Patients With Primary Breast Cancer: Long-Term Follow-Up (> 25 years) of the Phase III SBII:2pre Trial.

    Science.gov (United States)

    Ekholm, Maria; Bendahl, Pär-Ola; Fernö, Mårten; Nordenskjöld, Bo; Stål, Olle; Rydén, Lisa

    2016-07-01

    The aim of this study was to evaluate the long-term effect of 2 years of adjuvant tamoxifen compared with no systemic treatment (control) in premenopausal patients with breast cancer over different time periods through long-term (> 25 years) follow-up. Premenopausal patients with primary breast cancer (N = 564) were randomly assigned to 2 years of tamoxifen (n = 276) or no systemic treatment (n = 288). Data regarding date and cause of death were obtained from the Swedish Cause of Death Register. End points were cumulative mortality (CM) and cumulative breast cancer-related mortality (CBCM). The median follow-up for the 250 patients still alive in April 2014 was 26.3 years (range, 22.7 to 29.7 years). In patients with estrogen receptor-positive tumors (n = 362), tamoxifen was associated with a marginal reduction in CM (hazard ratio [HR], 0.77; 95% CI, 0.58 to 1.03; P = .075) and a significant reduction in CBCM (HR, 0.73; 95% CI, 0.53 to 0.99; P = .046). The effect seemed to vary over time (CM years 0 to 5: HR, 1.05; 95% CI, 0.64 to 1.73; years > 5 to 15: HR, 0.58; 95% CI, 0.37 to 0.91; and after 15 years: HR, 0.82; 95% CI, 0.48 to 1.42; CBCM years 0 to 5: HR, 1.09; 95% CI, 0.65 to 1.82; years > 5 to 15: HR, 0.53; 95% CI, 0.33 to 0.86; and after 15 years: HR, 0.72; 95% CI, 0.36 to 1.44). Two years of adjuvant tamoxifen resulted in a long-term survival benefit in premenopausal patients with estrogen receptor-positive primary breast cancer. © 2016 by American Society of Clinical Oncology.

  19. Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: A Dutch TEAM trial analysis

    NARCIS (Netherlands)

    J.G.H. van Nes; L.V. Beex (Louk); C.M. Seynaeve (Caroline); H. Putter (Hein); A. Sramek (Alexandr); S. Lardenoije (Susanne); M.D.-D.E. Carpentier (Marjolijn Duijm-D.E.); I. Van Rongen (Inge); J.W.R. Nortier (Johan W. R.); H.M. Zonderland (Harmine); C.J.H. van de Velde (Cornelis)

    2015-01-01

    textabstractBackground. Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane

  20. Selective use of adjuvant radiation therapy in resectable colorectal adenocarcinoma

    International Nuclear Information System (INIS)

    Cohen, A.M.; Gunderson, L.L.; Welch, C.E.

    1981-01-01

    Colorectal cancer recurs within the operative field in 10-20 per cent of patients undergoing potentially curative surgery. In certain subgroups, the recurrence rate is 20-50 per cent. There are some data to suggest either preoperative or postoperative radiation therapy as an adjuvant to potentially curative surgery can reduce the local operative failure rate. However, since radiation therapy has significant side effects, patient selection to maximize the therapeutic ratio is important. This report defines the criteria at the Massachusetts General Hospital for selection of patients with colorectal cancer for adjuvant radiation therapy, defines radiation therapy-surgery sequencing alternatives used, and describes techniques to reduce radiation side effects. Over a period of three and a half years, 196 patients received adjuvant radiation therapy: 51 patients received either moderate or low dose preoperative radiation therapy to rectal or rectosigmoid cancers, and 161 patients received postoperative radiation therapy to the pelvis or extrapelvic colonic tumor-lymph node beds. Some patients who received low-dose preoperative radiation therapy also received moderate-dose postoperative radiation therapy. We prefer moderate-dose postoperative radiation therapy as the approach most likely to decrease the local recurrence rate with minimal interference with surgical procedures and late small-bowel complications. Patients who received postoperative radiation therapy were those without distant metastases, whose primary tumor pathology revealed macroscopic or extensive microscopic transmural tumor penetration into extraperitoneal tissues. Careful case selection, multiple field techniques, the use of reperitonealization, omental flaps, and retroversion of the uterus into the pelvis were combined with postoperative small-bowel x-rays, bladder distention, and lateral portals to minimize radiation damage to normal structures

  1. Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis.

    Science.gov (United States)

    Hurley, Matthew N; Forrester, Douglas L; Smyth, Alan R

    2013-06-05

    Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, are urgently needed. To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis. We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings.Date of most recent search: 26 July 2012.We also searched MEDLINE (all years) on 23 February 2013 and ongoing trials registers on 13 February 2013. Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis. The authors independently assessed and extracted data from identified studies. We identified eighteen studies of which four are included that examined antibiotic adjuvant therapies, three studies are ongoing. The included studies involve the assessment of β-carotene, garlic and zinc supplementation and KB001 (a biological agent). No therapy demonstrated a significant effect upon pulmonary function, pulmonary exacerbations or quality of life. The study of zinc supplementation reports a reduction in the requirement of oral antibiotics but not of intravenous antibiotics, an effect that is difficult to understand.  We could not identify an antibiotic adjuvant therapy that could be recommended for the

  2. The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor-positive early-stage breast cancer

    International Nuclear Information System (INIS)

    Fowble, Barbara; Fein, Douglas A.; Hanlon, Alexandra L.; Eisenberg, Burton L.; Hoffman, John P.; Sigurdson, Elin R.; Daly, Mary B.; Goldstein, Lori J.

    1996-01-01

    Purpose: To evaluate the impact of tamoxifen on breast recurrence, cosmesis, complications, overall and cause-specific survival in women with Stage I-II breast cancer and estrogen receptor positive tumors undergoing conservative surgery and radiation. Methods and Materials: From 1982 to 1991, 491 women with estrogen receptor positive Stage I-II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median age of the patient population was 60 years with 21% < 50 years of age. The median follow-up was 5.3 years (range 0.1 to 12.8). Sixty-nine percent had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49% and the final margin of resection was negative in 64%. One hundred fifty-four patients received tamoxifen and 337 patients received no adjuvant therapy. None of the patients received adjuvant chemotherapy. Results: There were no significant differences between the two groups for age, race, clinical tumor size, histology, the use of reexcision, or median total dose to the primary. Patients who received tamoxifen were more often axillary node positive (44% tamoxifen vs. 5% no tamoxifen), and, therefore, a greater percentage received treatment to the breast and regional nodes. The tamoxifen patients less often had unknown margins of resection (9% tamoxifen vs. 22% no tamoxifen). The 5-year actuarial breast recurrence rate was 4% for the tamoxifen patients compared to 7% for patients not receiving tamoxifen (p 0.21). Tamoxifen resulted in a modest decrease in the 5-year actuarial risk of a breast recurrence in axillary node-negative patients, in those with unknown or close margins of resection, and in those who underwent a single excision. Axillary node-positive patients had a clinically significant decrease in the 5-year actuarial breast recurrence rate (21 vs. 4%; p 0.08). The 5-year actuarial rate of distant metastasis was not significantly decreased by the addition of adjuvant tamoxifen in all

  3. Corticosteroids as adjuvant therapy for ocular toxoplasmosis.

    Science.gov (United States)

    Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

    2017-01-26

    Ocular infection caused by Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea, and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 December 2016. We had planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids. Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as 'unsure' or 'include' after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion. We identified no completed or ongoing trial that was eligible for this Cochrane review. Although research has identified a wide

  4. Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy.

    Science.gov (United States)

    Derzko, C; Elliott, S; Lam, W

    2007-12-01

    Treatment with aromatase inhibitors for postmenopausal women with breast cancer has been shown to reduce or obviate invasive procedures such as hysteroscopy or curettage associated with tamoxifen-induced endometrial abnormalities. The side effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar to that seen with the natural events of aging. The consequences often include vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn may result in cystitis and vaginitis. Not surprisingly, painful intercourse (dyspareunia) and loss of sexual interest (decreased libido) frequently occur as well. Various interventions, both non-hormonal and hormonal, are currently available to manage these problems. The purpose of the present review is to provide the practitioner with a wide array of management options to assist in treating the sexual consequences of aromatase inhibitors. The suggestions in this review are based on recent literature and on the recommendations set forth both by the North American Menopause Association and in the clinical practice guidelines of the Society of Gynaecologists and Obstetricians of Canada. The complexity of female sexual dysfunction necessitates a biopsychosocial approach to assessment and management alike, with interventions ranging from education and lifestyle changes to sexual counselling, pelvic floor therapies, sexual aids, medications, and dietary supplements-all of which have been reported to have a variable, but often successful, effect on symptom amelioration. Although the use of specific hormone replacement-most commonly local estrogen, and less commonly, systemic estrogen with or without an androgen, progesterone, or the additional of an androgen in an estrogenized woman (or a combination)-may be highly effective, the concern remains that in patients with estrogen-dependent breast cancer, including those receiving anti-estrogenic adjuvant therapies, the use of these hormones may be

  5. The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

    International Nuclear Information System (INIS)

    Kim, Hyun-Ah; Ahn, Sei Hyun; Nam, Seok Jin; Park, Seho; Ro, Jungsil

    2016-01-01

    Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy

  6. Long-Term Data from 20 Trials Confirm Tamoxifen's Long-Lasting Benefit

    Science.gov (United States)

    Women with estrogen receptor-positive breast cancer who received about 5 years of adjuvant tamoxifen had a lower risk of recurrence in the 15 years after treatment than women who did not receive tamoxifen.

  7. Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients

    NARCIS (Netherlands)

    Kool, M.; Fontein, D. B. Y.; Meershoek-Klein Kranenbarg, E.; Nortier, J. W. R.; Rutgers, E. J. T.; Marang-van de Mheen, P. J.; van de Velde, C. J. H.

    2015-01-01

    Objectives: The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for

  8. Tamoxifen induces a pluripotency signature in breast cancer cells and human tumors.

    Science.gov (United States)

    Notas, George; Pelekanou, Vassiliki; Kampa, Marilena; Alexakis, Konstantinos; Sfakianakis, Stelios; Laliotis, Aggelos; Askoxilakis, John; Tsentelierou, Eleftheria; Tzardi, Maria; Tsapis, Andreas; Castanas, Elias

    2015-11-01

    Tamoxifen is the treatment of choice in estrogen receptor alpha breast cancer patients that are eligible for adjuvant endocrine therapy. However, ∼50% of ERα-positive tumors exhibit intrinsic or rapidly acquire resistance to endocrine treatment. Unfortunately, prediction of de novo resistance to endocrine therapy and/or assessment of relapse likelihood remain difficult. While several mechanisms regulating the acquisition and the maintenance of endocrine resistance have been reported, there are several aspects of this phenomenon that need to be further elucidated. Altered metabolic fate of tamoxifen within patients and emergence of tamoxifen-resistant clones, driven by evolution of the disease phenotype during treatment, appear as the most compelling hypotheses so far. In addition, tamoxifen was reported to induce pluripotency in breast cancer cell lines, in vitro. In this context, we have performed a whole transcriptome analysis of an ERα-positive (T47D) and a triple-negative breast cancer cell line (MDA-MB-231), exposed to tamoxifen for a short time frame (hours), in order to identify how early pluripotency-related effects of tamoxifen may occur. Our ultimate goal was to identify whether the transcriptional actions of tamoxifen related to induction of pluripotency are mediated through specific ER-dependent or independent mechanisms. We report that even as early as 3 hours after the exposure of breast cancer cells to tamoxifen, a subset of ERα-dependent genes associated with developmental processes and pluripotency are induced and this is accompanied by specific phenotypic changes (expression of pluripotency-related proteins). Furthermore we report an association between the increased expression of pluripotency-related genes in ERα-positive breast cancer tissues samples and disease relapse after tamoxifen therapy. Finally we describe that in a small group of ERα-positive breast cancer patients, with disease relapse after surgery and tamoxifen treatment, ALDH

  9. Adjuvant radiation therapy versus surgery alone in operable breast cancer

    International Nuclear Information System (INIS)

    Rutqvist, L.E.; Pettersson, D.; Johansson, H.

    1993-01-01

    This paper presents long-term results from a randomized trial of pre- or postoperative megavoltage radiation therapy versus surgery alone in pre- and postmenopausal women with operable breast cancer. Treatment outcome after relapse among patients who developed loco-regional recurrences was also analyzed. A total of 960 patients were included in the trial. The mean follow-up was 16 years (range: 13-19 years). The radiation therapy was individually planned. It included the chest wall (and the breast in the preoperative cases) and the regional lymph nodes. The tumor dose was 45 Gy/5 weeks. No adjuvant systemic therapy was used. The results showed a significant benefit with radiation therapy in terms of recurrence-free survival during the entire follow-up period. There was also an overall survival difference - corresponding to 16% reduction of deaths - in favour of the irradiated patients which, however, was not statistically significant (p=0.09). Among those 169 patients who developed loco-regional recurrences long-term control was only achieved in about one-third of the cases. This figure was similar among those who had received adjuvant radiation therapy (34%) compared to those initially treated with surgery alone (32%). This implied that the overall proportion of patients who eventually developed uncontrolled local disease was significantly higher among those initially allocated to surgery alone (16%) compared to those allocated to pre- or postoperative radiation therapy (6%, p<0.01). These results suggest that local undertreatment may be deleterious in subgroups of patients. (author) 5 tabs

  10. Adjuvant radiation therapy for pancreatic cancer: a 15-year experience

    International Nuclear Information System (INIS)

    Dobelbower, Ralph R.; Merrick, Hollis W.; Khuder, Sadik; Battle, Joyce A.; Herron, Lisa M.; Pawlicki, Todd

    1997-01-01

    Purpose: A retrospective analysis to determine differences in survival of patients with pancreatic aden carcinoma treated by radical surgery with and without adjuvant radiation therapy. Methods and Materials: Between 1980 and 1995, 249 patients with pancreatic tumors were identified at the Medical College of Ohio. Forty-four of these patients underwent radical surgical procedures with curative intent. These patients were divided into four groups according to treatment: surgery alone (n = 14), surgery plus intraoperative radiation therapy (IORT) (n = 6), surgery plus external beam radiation therapy (EBRT) (n = 14), or surgery plus both IORT and EBRT (n = 10). Outcome and survival were analyzed among the four groups. Results: The median survival time of patients treated with radical surgery alone was 6.5 months. The median survival time for the surgery plus IORT group was 9 months; however, 33.3% (two of six) of these patients survived longer than 5 years. This survival pattern was borderline significantly better than that for the surgery alone group (p = 0.0765). The surgery plus EBRT and the surgery plus IORT and EBRT groups had median survival times of 14.5 and 17.5 months, respectively. These were significantly better than that of the surgery alone group (p = 0.0004 and p = 0.0002, respectively). The addition of radiation therapy did not affect the treatment complication rate. Conclusion: The survival of patients who were treated with radical surgery alone was significantly poorer than that of patients who received adjuvant radiation therapy. These results are consistent with other studies in the literature. Patients treated with all three modalities (surgery, IORT, and EBRT) displayed the best median survival time

  11. Detection of tamoxifen metabolites by GC-MSD.

    Science.gov (United States)

    Báez, H; Camargo, C; Osorio, H; Umpiérrez, F

    2004-01-01

    Tamoxifen is an antiestrogen used in the adjuvant endocrine therapy of early breast cancer and malignant breast disorders. It is also used in women with anovulatory infertility caused by its stimulating effect on the secretion of the pituitary gonadotrophic hormones. In males it could increase the endogenous production of androgens. Because of these properties tamoxifen may be misused in some sports to treat the androgens suppression caused by the extensive abuse of anabolic androgenic steroids. A method for identification and confirmation of tamoxifen metabolites is described. Hydroxymetoxytamoxifen is detected in urine by gas chromatography and mass spectrometry in a selective ion monitoring method followed by the routine postrun in the screening of anabolic steroids. Once the hydroxymetoxytamoxifen is detected, confirmation of reported metabolites could be performed with a 5973 mass selective detector in the scan mode after solid-phase extraction by cationic exchange. This study also reports an excretion profile for a single dose of tamoxifen equivalent to 40 mg administrated orally to two males volunteers.

  12. Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study

    DEFF Research Database (Denmark)

    Colleoni, Marco; Giobbie-Hurder, Anita; Regan, Meredith M

    2011-01-01

    Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged ov...

  13. Azithromycin as an adjuvant therapy in cryptogenic organizing pneumonia

    Directory of Open Access Journals (Sweden)

    A.P. Vaz

    2011-07-01

    Full Text Available There are data about the immunomodulatory properties of some macrolides in cryptogenic organizing pneumonia (COP as an alternative to corticosteroids in mild disease or as adjuvant to standard therapy.A sixty-year-old female, with a controlled intrinsic asthma, presented with COP and recurrent respiratory exacerbations despite corticosteroid and immunossupressant therapy. Azithromycin (500 mg, on alternate days as an adjuvant to steroids was then started, with clinical and functional improvement and regression of lung infiltrates. Withdrawal of steroids was possible in one year, without evidence of relapse in the next six months. Azithromycin was maintained (three times per week with no documentation of adverse side effects.This clinical case reinforces the potential role of macrolides anti-inflammatory properties in COP as corticosteroids adjuvant therapy. Resumo: Existem dados na literatura sobre o uso das propriedades imunomoduladoras de alguns macrólidos no tratamento da pneumonia organizativa criptogénica (COP como alternativa aos corticoesteróides na doença ligeira ou como adjuvantes da terapêutica padrão.Os autores descrevem o caso de uma mulher de 60 anos de idade, com asma intrínseca controlada, que apresentou uma COP e exacerbações respiratórias de repetição, apesar da corticoterapia e terapêutica imunossupressora instituídas. Após início de azitromicina (500 mg, dias alternados, como adjuvante da corticoterapia, verificou-se melhoria clínica e funcional e regressão dos infiltrados pulmonares. A suspensão dos corticoesteróides foi possível no período de um ano, sem evidência de recidiva nos seis meses seguintes. A azitromicina foi mantida (3 vezes/semana sem documentação de efeitos laterais adversos.Este caso clínico reforça o potencial papel das propriedades anti-inflamatórias dos macrólidos na COP, como terapêutica adjuvante dos corticoesteróides. Keywords: Cryptogenic organizing pneumonia, Macrolides

  14. Adjuvant Intraoperative Photodynamic Therapy in Head and Neck Cancer

    Science.gov (United States)

    Rigual, Nestor R.; Shafirstein, Gal; Frustino, Jennifer; Seshadri, Mukund; Cooper, Michele; Wilding, Gregory; Sullivan, Maureen A.; Henderson, Barbara

    2015-01-01

    IMPORTANCE There is an immediate need to develop local intraoperative adjuvant treatment strategies to improve outcomes in patients with cancer who undergo head and neck surgery. OBJECTIVES To determine the safety of photodynamic therapy with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with surgery in patients with head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS Nonrandomized, single-arm, single-site, phase 1 study at a comprehensive cancer center among 16 adult patients (median age, 65 years) with biopsy-proved primary or recurrent resectable head and neck squamous cell carcinoma. INTERVENTIONS Intravenous injection of HPPH (4.0 mg/m2), followed by activation with 665-nm laser light in the surgical bed immediately after tumor resection. MAIN OUTCOMES AND MEASURES Adverse events and highest laser light dose. RESULTS Fifteen patients received the full course of treatment, and 1 patient received HPPH without intraoperative laser light because of an unrelated myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6 patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient, who received HPPH only). The most frequent adverse events related to photodynamic therapy were mild to moderate edema (9 patients) and pain (3 patients). One patient developed a grade 3 fistula after salvage laryngectomy, and another patient developed a grade 3 wound infection and mandibular fracture. Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter). The highest laser light dose was 75 J/cm2. CONCLUSIONS AND RELEVANCE The adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous cell carcinoma seems safe and deserves further study. PMID:23868427

  15. The role of hormonal therapy in patients with relapsed high-grade ovarian carcinoma: a retrospective series of tamoxifen and letrozole.

    Science.gov (United States)

    George, Angela; McLachlan, Jennifer; Tunariu, Nina; Della Pepa, Chiara; Migali, Cristina; Gore, Martin; Kaye, Stan; Banerjee, Susana

    2017-06-30

    Hormonal therapy is used as a treatment option in high-grade ovarian carcinoma (HGOC), but the role and choice of treatment remains unclear. Agents used include tamoxifen and aromatase inhibitors. Our aim was to evaluate the efficacy of tamoxifen (T) and letrozole (L) in HGOC in clinical practice and investigate factors influencing clinical outcome. A retrospective review of patients with relapsed HGOC treated with either tamoxifen or letrozole at the Royal Marsden Hospital between 2007 and 2012 was performed. The primary endpoint of the study was objective response rate (ORR). Secondary endpoints included CA125 response, clinical benefit rate (CBR) and duration of response. Platinum-sensitivity and ER-status were evaluated as predictors of treatment response. 97 patients were included (43 T, 54 L); median age 63 years (20-92); 91% high-grade serous; median number of lines of prior chemotherapy 3 (1-8); 60% platinum-resistant, 40% platinum-sensitive; 52% ER + ve, 1% ER-ve, 47% unknown. 14 patients (6 T, 8 L) achieved a partial response, with ORR (RECIST) of 14% (T) and 15% (L). The CBR for ≥3 months was 65% (22/43) for tamoxifen and 56% (22/54) for letrozole. There was no significant difference in ORR (p = 0.99) or CBR (p = 0.14) between tamoxifen and letrozole. 22 patients (23%) had a CA-125 response with hormonal therapy (10 T - 23% and 12 L - 22%). ORR did not differ by platinum sensitivity (p = 0.42); or ER-status (positive vs unknown, p = 0.12). Responders to letrozole had longer durations of response than responders to tamoxifen (26 vs 11.5 months, p = 0.03), but equivalent disease stability duration (9.6 vs 7.2 months respectively, p = 0.11). Within the constraints of a retrospective study, we identified that patients treated with letrozole had a significantly longer duration of response than those treated with tamoxifen. Treatment with either tamoxifen or letrozole is a rational treatment option for patients with ER + ve HGOC

  16. Transcutaneous electrical nerve stimulation therapy: An adjuvant pain controlling modality in TMD patients - A clinical study

    Directory of Open Access Journals (Sweden)

    Muhammad Shanavas

    2014-01-01

    Conclusion: The observed data suggest that TENS therapy can be used as an adjuvant modality in the management of pain associated with TMDs. This study justifies the use of TENS therapy in the management of TMD.

  17. Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

    Science.gov (United States)

    Zhu, Xin Yan; Liu, Fei

    2017-04-01

    Over 80% of individuals infected with Helicobacter pylori (H. pylori) are asymptomatic. Increased resistance to antibiotics and decreased compliance to the therapeutic regimens have led to the failure of eradication therapy. Probiotics, with direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials, have recently been used as a supplementary treatment in H. pylori eradication therapy. Probiotics have been considered useful because of the improvements in H. pylori eradication rates and therapy-related side effects although treatment outcomes using probiotics are controversial due to the heterogeneity of species, strains, doses and therapeutic duration of probiotics. Thus, despite the positive role of probiotics, several factors need to be further considered during their applications. Moreover, adverse events of probiotic use need to be noted. Further investigations into the safety of adjuvant probiotics to H. pylori eradication therapy are required. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  18. A nanomedicine based combination therapy based on QLPVM peptide functionalized liposomal tamoxifen and doxorubicin against Luminal A breast cancer.

    Science.gov (United States)

    Wang, Xiaoyou; Chen, Xianhui; Yang, Xiucong; Gao, Wei; He, Bing; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Dai, Zhifei; Zhang, Qiang

    2016-02-01

    Though combination chemotherapy or antitumor nanomedicine is extensively investigated, their combining remains in infancy. Additionally, enhanced delivery of estrogen or its analogs to tumor with highly-expressed estrogen-receptor (ER) is seldom considered, despite its necessity for ER-positive breast cancer treatment. Here, nanomedicine based combination therapy using QLPVM conjugated liposomal tamoxifen (TAM) and doxorubicin (DOX) was designed and testified, where the penta-peptide was derived from Ku70 Bax-binding domain. Quantitative, semi-quantitative and qualitative approaches demonstrated the enhanced endocytosis and cytotoxicity of QLPVM conjugated sterically stabilized liposomes (QLPVM-SSLs) in vitro and in vivo. Mechanism studies of QLPVM excluded the possible electrostatic, hydrophobic or receptor-ligand interactions. However, as a weak cell-penetrating peptide, QLPVM significantly induced drug release from QLPVM-SSLs during their interaction with cells, which was favorable for drug internalization. These findings suggested that the nanomedicine based combination therapy using QLPVM-SSL-TAM and QLPVM-SSL-DOX might provide a rational strategy for Luminal A breast cancer. Breast cancer remains a leading cause of mortality in women worldwide. Although combined therapy using hormonal antagonist and chemotherapy is the norm nowadays, the use of these agents together in a single delivery system has not been tested. Here, the authors investigated this approach using QLPVM conjugated liposomes in in-vitro and in-vivo models. The positive findings may provide a novel direction for breast cancer treatment in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Endocrine therapy in premenopausal women with breast cancer: a critical appraisal of current evidence.

    Science.gov (United States)

    Montemurro, Filippo; Del Mastro, Lucia; De Laurentiis, Michele; Puglisi, Fabio

    2016-01-01

    Nearly 60% of all breast cancer premenopausal women are diagnosed with a hormone receptor positive tumor and, therefore, are candidates for adjuvant hormonal therapy. Treatment with tamoxifen for at least 5 years has been for a long time the standard of care, as it is associated with overall positive clinical outcomes. However, in the last decade, a number of studies on adjuvant endocrine therapy in premenopausal women with hormone receptor positive breast cancer have been published, adding a bulk of evidence to existing knowledge in this field. A critical appraisal of their results appears necessary in order to put the recently collected data into the current framework of treatment, and to discuss the several issues that remain open. Here, we review the most recent evidence on the following: the optimal duration of tamoxifen treatment, results of the studies comparing tamoxifen alone to tamoxifen plus ovarian function suppression (OFS), results of the studies comparing tamoxifen plus OFS to aromatase inhibitors plus OFS.

  20. Adjuvant photodynamic therapy in surgical management of cerebral tumors

    Science.gov (United States)

    Chen, Zong-Qian; Wu, Si-En; Zhu, Shu-Gan

    1993-03-01

    We have performed high dose photoradiation therapy in patients with cerebral tumors. Twenty-seven patients had gliomas, two had metastatic cancer of the brain, one had malignant meningioma. Hematoporphyrin derivative was administered intravenously. All patients underwent a craniotomy with a radical or partial excision of the tumor. There was no evidence of increased cerebral edema and other toxicity from the therapy, and all patients were discharged from the hospital within 15 days after surgery. On the basis of animal experiments our institute started using photodynamic therapy (PDT) as an adjuvant measure to the operative therapy in 30 cases of cerebral tumors. Ten of these patients were excluded from this group because of the short postoperative following time. Here, the details of our experiences are presented as follows: 106 of C6 type glioma cell strain were implanted into the frontal lobe of a Chinese hamster. Fourteen days later intracranial gliomas developed, which were larger than 4 mm in diameter, HpD in a dosage of 4 mg/kg was injected into the tail vein of the animals. The fluorescence was seen 5 minutes later. The diagnostic laser used was He-Ca (Hc-type 15A, made at Shanghai Laser Institute) with a wavelength of 441.6 nm, power of 30 mw. The fluorescence reached its peak point 24 hours later, and the normal tissue can be identified by the lack of fluorescence. Then, the tumor tissue was further radiated with an Ar laser (made in Nanjing Electronic Factory, type 360), pumped dye-laser (made in Changchun Optic Machinery Institute, type 901) with a wavelength of 630 nm, and an energy density of more than 200 Joules/cm2, which might get the tumor cells destroyed selectively. The effect of photoradiation may reach as deep as 4 - 7 mm into the brain tissue without cerebral edema or necrosis.

  1. Comparative effects of adjuvant cimetidine and omeprazole during pancreatic enzyme replacement therapy

    NARCIS (Netherlands)

    Bruno, M. J.; Rauws, E. A.; Hoek, F. J.; Tytgat, G. N.

    1994-01-01

    In a double-blind, randomized crossover study, the hypotheses were tested that more powerful inhibition of gastric acid secretion by adjuvant omeprazole further improves the efficacy of pancreatic enzyme replacement therapy compared to adjuvant cimetidine and that excluding the influence of

  2. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    International Nuclear Information System (INIS)

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    2013-01-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

  3. Physical activity for women with breast cancer after adjuvant therapy.

    Science.gov (United States)

    Lahart, Ian M; Metsios, George S; Nevill, Alan M; Carmichael, Amtul R

    2018-01-29

    Women with a diagnosis of breast cancer may experience short- and long-term disease and treatment-related adverse physiological and psychosocial outcomes. These outcomes can negatively impact prognosis, health-related quality of life (HRQoL), and psychosocial and physical function. Physical activity may help to improve prognosis and may alleviate the adverse effects of adjuvant therapy. To assess effects of physical activity interventions after adjuvant therapy for women with breast cancer. We searched the Cochrane Breast Cancer Group (CBCG) Specialised Registry, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Physiotherapy Evidence Database (PEDro), SPORTDiscus, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform, on 18 September 2015. We also searched OpenGrey and Healthcare Management Information Consortium databases. We searched for randomised and quasi-randomised trials comparing physical activity interventions versus control (e.g. usual or standard care, no physical activity, no exercise, attention control, placebo) after adjuvant therapy (i.e. after completion of chemotherapy and/or radiation therapy, but not hormone therapy) in women with breast cancer. Two review authors independently selected studies, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when needed. We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome and used GRADE to assess the quality of evidence for the most important outcomes. We included 63 trials that randomised 5761 women to a physical activity intervention (n = 3239) or to a control (n = 2524). The duration of interventions ranged from 4 to 24 months, with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included aerobic exercise only, 21 involved aerobic

  4. Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

    DEFF Research Database (Denmark)

    Phillips, Kelly-Anne; Milne, Roger L; Rookus, Matti A

    2013-01-01

    To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers.......To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers....

  5. Randomized controlled trial of adjuvant oral dexamethasone pulse therapy in pemphigus vulgaris - PEMPULS trial

    NARCIS (Netherlands)

    Mentink, LF; Mackenzie, MW; Toth, GG; Laseur, M; Lambert, FPG; Veeger, NJGM; Cianchini, G; Pavlovic, MD; Jonkman, MF

    Objective: To determine the therapeutic effect of adjuvant dexamethasone pulse therapy when given in addition to conventional treatment of pemphigus vulgaris. Design: A randomized, placebo-controlled trial. Setting: International European, multicenter outpatient and inpatient study. Patients: Of the

  6. [Adjuvant systemic antibiotic therapy for surgically treated spondylodiscitis].

    Science.gov (United States)

    Marmelstein, D; Homagk, N; Hofmann, G O; Röhl, K; Homagk, L

    2015-04-01

    Recognised methods for the treatment of spondylodiscitis in correspondence to the immobilisation are systemic antibiotic therapy. However, the available data for recommendations of specific antibiotic therapy are very heterogeneous. The aim of this study was to focus on the adjuvant antibiotic therapy in surgical treated cases of spondylodiscitis and to reach a guideline regarding its application in patients' spondylodiscitis. Between 01.10.1998 and 31.12.2011 276 inpatient cases of spondylodiscitis were surgically treated, documented and included in the study. The study involved medical history, germ status, localisation and extent of spondylodiscitis and antibiotic treatment. Between 01.01.2012 and 31.12.2013 a further 20 cases of spondylodiscitis were treated according to a standardised treatment regimen of antibiotic therapy and included in the study. The age distribution shows a marked prominence of 60 to 80 year-olds, with a leading localisation of spondylodiscitis in the lumbar spine with 55 % followed by the thoracic spine (33 %) and the cervical spine (12 %). A constant observation during the study periods was the delayed diagnosis of more than 1 month of spondylodiscitis, so that about 60 % of the patients were not receiving any treatment for their disease at the time of hospitalisation. The aetiology of spondylodiscitis is very heterogeneous and remained unknown in 34 % of cases. However, diabetes mellitus appeared as a disease favouring the occurrence of spondylodiscitis since it was concomitant with almost 50 % of patients with spondylodiscitis. The bacterial spectrum is limited in our area to staphylococci, with a predominance of Staphylococcus aureus. At least about 10 % of the germs are multi-drug resistant. In 45 % of cases, pathogen detection was unsuccessful. Clindamycin is the most commonly used antibiotic in the treatment of spondylodiscitis and is used in 26.8 % in combinations with other antibiotics. The antibiotic therapy

  7. Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy – A single-arm phase II study

    Directory of Open Access Journals (Sweden)

    Hanan Shawky

    2014-12-01

    Conclusion: One year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy.

  8. Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma

    International Nuclear Information System (INIS)

    Hamilton, Chad A.; Liou, W.-S.; Osann, Kathryn; Berman, Michael L.; Husain, Amreen; Teng, Nelson N.; Kapp, Daniel S.; Chan, John K.

    2005-01-01

    Purpose: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. Methods and Materials: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. Results: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. Conclusion: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma

  9. Women prefer adjuvant endocrine therapy to chemotherapy for breast cancer treatment.

    Science.gov (United States)

    Niikura, Naoki; Kimura, Morihiko; Iwamoto, Takayuki; Hayashi, Naoki; Shintoku, Junichi; Saito, Yuki; Suzuki, Yasuhiro; Tokuda, Yutaka

    2013-01-01

    We attempted to determine the preferences of women regarding the benefits they considered necessary to make adjuvant therapy worthwhile, and to compare preferences for adjuvant endocrine therapy, chemotherapy, and trastuzumab therapy. We also investigated the effect of information about cost on women's treatment preferences. Consecutive women who had a medical examination at the Breast Clinic, Ota General Hospital, were included in our study. We collected a questionnaire from a total of 365 women; 297 completed responses were included in the study. Among 297 women, 105 had breast cancer that had been treated and 192 did not have breast cancer; 38% of women judged that a 5% or less gain in the probability of survival was sufficient to make endocrine therapy worthwhile; 28% of participants judged that chemotherapy was worthwhile; 24% of participants judged that trastuzumab therapy was worthwhile. Women indicated that they were more likely to receive adjuvant endocrine therapy than chemotherapy or trastuzumab therapy, for the same gains in the probability of survival. Cost information about treatments did not affect women's treatment preferences. Younger women tended to judge improvements in survival sufficient to make adjuvant endocrine and chemotherapy worthwhile, as compared to older women. The comparisons were statistically significant in the 10 and 20% categories for endocrine therapy and chemotherapy. Women prefer endocrine therapy to chemotherapy or trastuzumab therapy, given the same projected treatment benefits. Younger women prefer both chemotherapy and endocrine therapy as compared with older woman.

  10. Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials.

    Science.gov (United States)

    Regan, Meredith M; Pagani, Olivia; Francis, Prudence A; Fleming, Gini F; Walley, Barbara A; Kammler, Roswitha; Dell'Orto, Patrizia; Russo, Leila; Szőke, János; Doimi, Franco; Villani, Laura; Pizzolitto, Stefano; Öhlschlegel, Christian; Sessa, Fausto; Peg Cámara, Vicente; Rodríguez Peralto, José Luis; MacGrogan, Gaëtan; Colleoni, Marco; Goldhirsch, Aron; Price, Karen N; Coates, Alan S; Gelber, Richard D; Viale, Giuseppe

    2015-11-01

    The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-negative disease. Of 5707 women enrolled, 4115 with HER2-negative (HR+/HER2-) disease had ER, PgR, and Ki-67 centrally assessed by immunohistochemistry. Breast cancer-free interval (BCFI) was defined from randomization to first invasive local, regional, or distant recurrence or contralateral breast cancer. The prognostic and predictive values of ER, PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology. In this HR+/HER2- population, the median ER, PgR, and Ki-67 expressions were 95, 90, and 18 % immunostained cells. As most patients had strongly ER-positive tumors, the predictive value of ER levels could not be investigated. Lower PgR and higher Ki-67 expression were associated with reduced BCFI. There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels, though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression (OFS) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67. Women with poor prognostic features of low PgR and/or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone, but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2- early breast cancer.

  11. Assessing Prescribing Trends of Adjuvant Medication Therapy in Outpatients With a Diagnosis of Noncancer Chronic Pain.

    Science.gov (United States)

    Rasu, Rafia S; Vossen, Rachel K; Knell, Maureen E

    2017-09-01

    Chronic pain affects over 100 million adults in the United States, yet continues to be difficult to treat. Concerns continue to mount over the use of opioids to treat noncancer chronic pain (NCCP). Guidelines support the use of adjuvant medications as one of the preferred options for treating chronic pain over opioids. To examine reported usage of adjuvants in the treatment of chronic pain via the National Ambulatory Medical Care Survey (NAMCS). A retrospective, cross-sectional study evaluating reported usage of adjuvant pain medications for the treatment of NCCP was conducted using NAMCS data from 2000 to 2007. Weighted samples were analyzed with regard to several patient variables. Logistic regression models provided 95% confidence intervals and an adjusted odds ratio to determine statistically significant differences in reported usage for the evaluated patient variables. In total, 244,797,406 weighted visits were included for analysis. The analysis showed an almost 2-fold increase in adjuvant use during the study period. Statistically significant differences were identified for several factors evaluated. Younger age, female sex, care from a nonprimary care physician, comorbidities with pain, and >5 current medications were associated with higher rates adjuvant therapy use. Overall adjuvant usage dramatically increased during the study period. Analysis of data demonstrated adjuvant use in chronic pain varied based patient-specific characteristics. These results may allow clinicians, policy makers, and medical educators to identify potential gaps in adjuvant use in certain populations and target areas for clinical, populations-based, and educational improvements in managing NCCP.

  12. Endocrinology and hormone therapy in breast cancer: Endocrine therapy in premenopausal women

    International Nuclear Information System (INIS)

    Pritchard, Kathleen

    2005-01-01

    Endocrine therapy remains important in premenopausal women with hormone receptor positive breast cancer. Ovarian ablation, used alone, is effective in delaying recurrence and increasing survival in such women. When added to chemotherapy, it is less clear that it is effective perhaps because of the endocrine ablative effect of chemotherapy. Trials comparing ovarian ablation with or without tamoxifen to CMF-type chemotherapy suggest that the endocrine therapy is equivalent to or better than this chemotherapy in women whose tumors have estrogen and/or progesterone receptor. Tamoxifen is also effective in preventing recurrence and prolonging survival in the adjuvant setting in premenopausal women. While most of the available data deals with tamoxifen given alone, it appears to have a similar beneficial effect when added to chemotherapy in the premenopausal adjuvant setting. Adjuvant aromatase inhibitors should not be used in premenopausal women

  13. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  14. Clinical applications of post-surgical adjuvant radionuclide therapy in the treatment of serious hypertrophic scar

    International Nuclear Information System (INIS)

    Cao Weihong; Zhang Guixian

    2002-01-01

    Objective: To evaluate the efficacy of post-surgical adjuvant radionuclide therapy in treating patients with serious hypertrophic scars. Methods: Thirty-four cases of serious hypertrophic scars received surgical resection followed by 1 to 4 courses of topical contiguous 32 P and 90 Sr therapy. Results: The 34 cases were followed for 1 to 4 years after operation. Thirty cases reached the standard of cure and 4 cases relapsed. Conclusion: The efficacy of post-surgical adjuvant radionuclide therapy in severe hypertrophic scars is confirmed. The advantages of this treatment protocol include safe radiation dosage and convenience in wearing the radionuclide applicator

  15. MR imaging of the pelvis in the diagnosis of the endometrium in breast cancer patients in tamoxifen therapy

    International Nuclear Information System (INIS)

    Hauth, E.; Libera, H.; Forsting, M.; Kimmig, R.

    2006-01-01

    Purpose: The purpose of the study was to determine the value of MR imaging of the pelvis in the diagnostic work-up of the endometrium in breast cancer patients in tamoxifen therapy. Materials and methods: MR imaging of the pelvis was performed on 24 patients (mean: 62 years, range: 51-74 years) and 30 healthy women (mean: 65 years, range: 51-73 years). The volume of the uterus and cervix and the maximal thickness of the endometrium, junctional zone and myometrium of the uterus were determined and compared to the confidence interval of the parameters in healthy women. The Mann-Whitney U-test was used to identify differences in the volume of the uterus and cervix and in the thickness of the uterine wall layers in both groups. Results: A comparison of the volume of the uterus and cervix and the thickness of the uterine wall layers in the two groups yielded no significant differences. The volume of the uterus and cervix showed no statistical differences between the two groups. The maximal height of the endometrium in the patient group showed a mean of 0.6 cm (range: 0.1-2.2 cm), and a mean of 0.4 cm (range: 0.1-1.2 cm) in the group of healthy women. The differences were not statistically significant. In all healthy women the endometrium showed homogeneous signal intensity in the sagittal T2-weighted images. In 12 of the 24 breast cancer patients, the endometrium showed inhomogeneous signal intensity. In 9 of 12 patients with an inhomogeneous endometrium with a thickness equal to or greater than 0.6 cm, histopathology confirmed polyps. In 3 patients endometrium hyperplasia was found. In one patient histopathology revealed a polyp and an endometrium carcinoma in stage T1 a N0. The endometrium carcinoma was not able to be seen via MR imaging. (orig.)

  16. Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients.

    Science.gov (United States)

    Kool, M; Fontein, D B Y; Meershoek-Klein Kranenbarg, E; Nortier, J W R; Rutgers, E J T; Marang-van de Mheen, P J; van de Velde, C J H

    2015-06-01

    The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for its adverse events, which may negatively affect Quality of Life (QoL). The aim of this study is to assess the impact of extended adjuvant endocrine therapy on long-term QoL outcomes. 471 patients selected from the IDEAL trial were invited to complete a questionnaire 1-1.5 years after starting with extended therapy. The questionnaire consisted of the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Mean QoL outcomes were compared with EORTC reference values for stage I and II breast cancer patients and the general population. Furthermore, QoL outcomes were compared between different treatment regimens. A difference of eight points was considered clinically relevant. IDEAL patients receiving extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with reference values for stage I and II breast cancer patients (79.6 versus 64.6; p treatment regimens prior to extended adjuvant endocrine therapy, differences were only found on specific QoL domains (e.g. arm symptoms). Breast cancer patients on extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with other stage I-II breast cancer patients and the general population, 6-8.5 years after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I to IIIA Completely Resected Non-Small-Cell Lung Cancers: American Society of Clinical Oncology/Cancer Care Ontario Clinical Practice Guideline Update.

    Science.gov (United States)

    Kris, Mark G; Gaspar, Laurie E; Chaft, Jamie E; Kennedy, Erin B; Azzoli, Christopher G; Ellis, Peter M; Lin, Steven H; Pass, Harvey I; Seth, Rahul; Shepherd, Frances A; Spigel, David R; Strawn, John R; Ung, Yee C; Weyant, Michael

    2017-09-01

    Purpose The panel updated the American Society of Clinical Oncology (ASCO) adjuvant therapy guideline for resected non-small-cell lung cancers. Methods ASCO convened an update panel and conducted a systematic review of the literature, investigating adjuvant therapy in resected non-small-cell lung cancers. Results The updated evidence base covered questions related to adjuvant systemic therapy and included a systematic review conducted by Cancer Care Ontario current to January 2016. A recent American Society for Radiation Oncology guideline and systematic review, previously endorsed by ASCO, was used as the basis for recommendations for adjuvant radiation therapy. An update of these systematic reviews and a search for studies related to radiation therapy found no additional randomized controlled trials. Recommendations Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stage IIA, IIB, or IIIA disease who have undergone complete surgical resections. For individuals with stage IB, adjuvant cisplatin-based chemotherapy is not recommended for routine use. However, a postoperative multimodality evaluation, including a consultation with a medical oncologist, is recommended to assess benefits and risks of adjuvant chemotherapy for each patient. The guideline provides information on factors other than stage to consider when making a recommendation for adjuvant chemotherapy, including tumor size, histopathologic features, and genetic alterations. Adjuvant chemotherapy is not recommended for patients with stage IA disease. Adjuvant radiation therapy is not recommended for patients with resected stage I or II disease. In patients with stage IIIA N2 disease, adjuvant radiation therapy is not recommended for routine use. However, a postoperative multimodality evaluation, including a consultation with a radiation oncologist, is recommended to assess benefits and risks of adjuvant radiation therapy for each patient with N2 disease. Additional

  18. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    International Nuclear Information System (INIS)

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

    2011-01-01

    Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age ≥75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were ≥75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

  19. Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

    Science.gov (United States)

    Chung, Ki-Young Y; Kelsen, David

    2006-06-01

    The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

  20. Cost-effectiveness of anastrozole, in comparison with tamoxifen, in the adjuvant treatment of early breast cancer in Brazil Custo-efetividade do anastrozol em comparação com tamoxifeno no tratamento adjuvante do câncer de mama precoce no Brasil

    Directory of Open Access Journals (Sweden)

    Marcelo Fonseca

    2009-01-01

    Full Text Available OBJECTIVE: Breast cancer, a leading type of cancer in many developing countries, is the most frequent non-cutaneous tumor in Brazil. Hormone therapy is the standard of care in the adjuvant treatment of early-stage, hormone-receptor-positive disease, and both tamoxifen and third-generation aromatase inhibitors are options in postmenopausal women. The comparative cost-effectiveness of different treatment strategies is of considerable interest in societies facing limited resources. METHODS: In an attempt to compare cost-effectiveness of upfront treatment with tamoxifen or anastrozole, the medical and economic results in a hypothetical cohort of 64-year-old postmenopausal women, was analyzed considering the Brazilian healthcare system in 2005, the primary perspective of the private sector, and a lifetime horizon. Data from the ATAC Trial, Markov modeling, a modified Delphi panel, and microcosting (in Brazilian R$ were used to estimate costs and effectiveness of the two upfront strategies. RESULTS: The model estimated a gain of 0.55 discounted life-years for patients receiving anastrozole, relative to those treated with tamoxifen. With an incremental cost of R$ 15,141.15, the model estimated that the cost-effectiveness of anastrozole, in relation to tamoxifen, was R$ 27,326.80. Monte Carlo simulations showed that approximately 50% of the cases fell below the threshold of R$ 29,229.00 per life-year gained, which is recommended by the World Health Organization for Brazil. CONCLUSION: It was concluded that upfront anastrozole is a cost-effective option compared with tamoxifen in the adjuvant treatment of postmenopausal women with hormone-receptor-positive early breast cancer.RESUMO OBJETIVO: O câncer de mama, o mais comum em vários países desenvolvidos, é o tumor não cutâneo mais frequente no Brasil. A terapia hormonal é o tratamento adjuvante padrão para os estágios precoces, em doença com receptor hormonal positivo, e o tamoxifeno e os

  1. Examples of adjuvant treatment enhancing the antitumor effect of photodynamic therapy

    Science.gov (United States)

    Korbelik, Mladen; Cecic, Ivana; Sun, Jinghai; Chaplin, David J.

    1999-07-01

    Strategies for improving the clinical efficacy of photodynamic therapy (PDT) in treatment of solid cancers include applications of different types of adjuvant treatments in addition to this modality that may result in superior therapeutic outcome. Examples of such an approach investigated using mouse tumor models are presented in this report. It is shown that the cures of PDT treated subcutaneous tumors can be substantially improved by adjuvant therapy with: metoclopramide (enhancement of cancer cell apoptosis), combretastatin A-4 (selective destruction of tumor neovasculature), Roussin's Black Salt (light activated tumor localized release of nitric oxide), or dendritic cell-based adoptive immunotherapy (immune rejection of treated tumor).

  2. Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients

    OpenAIRE

    Maithili Karpaga Selvi, N.; Sridhar, M. G.; Swaminathan, R. P.; Sripradha, R.

    2014-01-01

    It is known that there is a significant interplay of insulin resistance, oxidative stress, dyslipidemia, and inflammation in type 2 diabetes mellitus (T2DM). The study was undertaken to investigate the effect of turmeric as an adjuvant to anti-diabetic therapy. Sixty diabetic subjects on metformin therapy were recruited and randomized into two groups (30 each). Group I received standard metformin treatment while group II was on standard metformin therapy with turmeric (2 g) supplements for 4 ...

  3. Depression related to (neo)adjuvant hormonal therapy for prostate cancer

    International Nuclear Information System (INIS)

    Tol-Geerdink, Julia J. van; Leer, Jan Willem; Lin, Emile N.J.T. van; Schimmel, Erik C.; Stalmeier, Peep F.M.

    2011-01-01

    Background: We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy. Methods: Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide + Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis. Results: During the course of hormonal therapy, depression was significantly heightened by both hormone use (p < 0.001) and poor prognosis (p < 0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p < 0.01). The increase was, however, small. Conclusions: Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

  4. Electrocardiography changes during adjuvant breast cancer therapy: incidence and risk factors.

    Science.gov (United States)

    Elme, Anneli; Saarto, Tiina; Tötterman, Karl Johan; Utrianen, Meri; Kautiainen, Hannu; Järvenpää, Salme; Tenhuen, Mikko; Blomqvist, Carl

    2013-11-01

    Breast cancer survivors have a higher cardiovascular morbidity/mortality rate, when compared with healthy age-matched general population. Electrocardiography (ECG) changes have been found to be associated with chemo- and radiation therapy. In the present study we investigated changes in ECG patterns following modern adjuvant therapy for breast cancer. A standard 12-lead electrocardiogram was recorded at rest three times (prior and after adjuvant therapy) and retrospectively analyzed in 414 breast cancer patients, who participated in the open prospective phase III randomized trial (BREX) of exercise training 2005-2007. New electrocardiographic changes in the T-wave or ST-segment (depression or elevation) after the adjuvant therapy were recorded in 49 patients (13%). In multivariate analyses, hypertension treated with anti-hypertensive medication was the only significant factor associated with irreversible ECG changes (OR=4.71; 95% CI=1.36-16.38; p=0.015). New irreversible pathological electrocardiographic changes, which acquired during the adjuvant therapy, had a clear relationship with hypertension This patients subgroup needs to be studied further.

  5. Therapeutic mammoplasty allows for clear surgical margins in large and multifocal tumours without delaying adjuvant therapy.

    Science.gov (United States)

    Bamford, Richard; Sutton, Richard; McIntosh, Jamie

    2015-04-01

    Therapeutic mammoplasty (TM) is suggested to have a number of advantages by comparison to standard breast conservation surgery in selected patients, however, data to support such assertions are sparse and outcomes remain uncertain. We assess the ability of TM to achieve some of its suggested benefits, specifically obtaining clear surgical margins (CSM) around large or multifocal tumours, and examine whether TM is associated with delay in administering adjuvant therapies. Data were extracted from a prospectively maintained database on all patients undergoing TM over 8 years. Key oncological outcomes and time to initiation of adjuvant therapies were recorded. Sixty eight patients underwent TM, sixty two for invasive disease and six for in-situ disease only. Tumour size ranged from 3 mm to 85 mm. Twenty-one (30.8%) patients received neo-adjuvant therapy, with 15 (22.0%) receiving chemotherapy and six (8.8%) receiving endocrine therapy prior to surgery. CSM were obtained in 65 patients (95.6%). Where margins were involved, two were due to Ductal Carcinoma in situ and one from undiagnosed invasive lobular cancer, resulting in one wider excision and two completion mastectomies. Radiotherapy was delayed in one patient with delayed wound healing. No local recurrence has been recorded. These data support the ability of TM to consistently achieve CSM around large and multifocal tumours in selected patients, with acceptable local control and minimal morbidity and delay in adjuvant therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Prevention of Gynecomastia and Breast Pain Caused by Androgen Deprivation Therapy in Prostate Cancer: Tamoxifen or Radiotherapy?

    Energy Technology Data Exchange (ETDEWEB)

    Arruda Viani, Gustavo, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil); Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil)

    2012-07-15

    Purpose: To determine, in a meta-analysis, whether gynecomastia and breast pain rates in men with prostate cancer treated with androgen deprivation therapy (ADT) are reduced if treated with prophylactic radiotherapy (RT) or tamoxifen (TMX). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing RT or TMX with observation for men with prostate cancer using ADT. Results: Six RCTs (three RT trials and three TMX trials, N = 777 patients total) were identified that met the study criteria. Pooled results from these RCTs comparing RT vs. observation showed a significant reduction in the incidence of gynecomastia and breast pain rates in patients treated with RT (odds ratio [OR] = 0.21, 95% confidence interval [CI] = 0.12-0.37, p < 0.0001, and OR = 0.34, 95% CI 0.20-0.57, p < 0.0001, respectively). Use of RT resulted in an absolute risk reduction (ARR) of 29.4% and 19.9%, with a number needed to treat (NNT) of 3.4 and 5 to avoid one case of gynecomastia and breast pain, respectively. Pooled results from trials comparing TMX vs. observation showed a statistical benefit for breast pain and gynecomastia in favor of TMX arms (OR = 0.04, 95% CI = 0.02-0.08, p < 0.0001 and OR = 0.07, 95% CI = 0.0-0.14, p < 0.00001). TMX resulted in an ARR = 64.1% and 47.6%, with an NNT of 1.56 and 2.1 to avoid one case of gynecomastia and breast pain, respectively. Considering adverse effects, TMX was 6 times more adverse effects than RT. Conclusions: Our data have shown that both TMX and RT prevented gynecomastia and breast pain in patients with prostate cancer receiving ADT for prostate cancer. Although TMX was two times more effective in preventing gynecomastia, RT should represent an effective and safe treatment option, to take into account mainly in patients with cardiovascular risk factors or thrombotic diathesis.

  7. Tabletted guar gum microspheres of piroxicam for targeted adjuvant therapy for colonic adenocarcinomas.

    Science.gov (United States)

    Vats, Anima; Pathak, Kamla

    2012-11-01

    In recent years, nonsteroidal anti-inflammatory drugs have been found to be cogent as an adjuvant therapeutic agent in mitigating colorectal cancer. Thus, this present investigation was aimed to formulate an oral, targeted tablet of piroxicam microspheres for sustained and targeted adjuvant therapy for colonic adenocarcinomas. Crosslinked guar gum microspheres of piroxicam were directly compressed into matrix tablet and coated with Eudragit S100. The optimized tablet that displayed 0% release in simulated gastric fluid, 15% in simulated intestinal fluid and 97.1% in simulated colonic fluid underwent roentgenographic study in rabbits to check its safe transit to the colon. x-ray images revealed intactness of the tablet until it reached the colon where the tablet matrix eroded. The designed, conceptual formulation emerged as potential carrier for targeted adjuvant therapy of piroxicam.

  8. “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice

    International Nuclear Information System (INIS)

    Sun, Xueying; Jiang, Ruohan; Przepiorski, Aneta; Reddy, Shiva; Palmano, Kate P; Krissansen, Geoffrey W

    2012-01-01

    Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers. In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg) were fed an Fe-Lf supplemented diet (5 g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed. Tamoxifen weakly (IC 50 ~ 8 μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations in vitro. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P < 0.001), respectively, compared to untreated controls. The combination therapy was significantly (all P < 0.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors. The results indicate that Fe-Lf is a potent

  9. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    International Nuclear Information System (INIS)

    McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A.; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

    2015-01-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered

  10. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    McMillan, Matthew T. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Ojerholm, Eric [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Roses, Robert E., E-mail: Robert.Roses@uphs.upenn.edu [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mamtani, Ronac [Department of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A. [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Stripp, Diana; Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Datta, Jashodeep [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  11. Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

    International Nuclear Information System (INIS)

    Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

  12. Clinical evidence on the magnitude of change in growth pathway activity in relation to Tamoxifen resistance is required.

    Science.gov (United States)

    Mansouri, Sepideh; Farahmand, Leila; Teymourzadeh, Azin; Majidzadeh-A, Keivan

    2017-08-08

    Despite prolonged disease-free survival and overall survival rates in estrogen receptor (ER)-positive patients undergoing adjuvant treatment, Tamoxifen therapy tends to fail due to eventual acquisition of resistance. Although numerous studies have emphasized the role of receptor tyrosine kinases (RTKs) in the development of Tamoxifen resistance, inadequate clinical evidence is available regarding the alteration of biomarker expression during acquired resistance, thus undermining the validity of the findings. Results of two meta-analyses investigating the effect of HER2 status on the prognosis of Tamoxifen-receiving patients have demonstrated that despite HER2-negative patients having longer disease-free survival; there is no difference in overhaul survival between the two groups. Furthermore, due to the intricate molecular interactions among estrogen receptors including ERα36, ERα66, and also RTKs, it is not surprising that RTK suppression does not restore Tamoxifen sensitivity. In considering such a complex network, we speculate that by the time HER2/EGFR is suppressed via targeted therapies, activation of ERα66 and ERα36 initiate molecular signaling pathways downstream of RTKs, thereby enhancing cell proliferation even in the presence of both Tamoxifen and RTK inhibitors. Although clinical findings regarding the molecular pathways downstream of RTKs have been thoroughly discussed in this review, further clinical studies are required in determining a consistency between preclinical and clinical findings. Discovering the best targets in preventing tumor progression requires thorough comprehension of estrogen-dependent and estrogen-independent pathways during Tamoxifen resistance development. Indeed, exploring additional clinically-proven targets would allow for better characterized treatments being available for breast cancer patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Combination treatment of tamoxifen with risperidone in breast cancer.

    Directory of Open Access Journals (Sweden)

    Wei-Lan Yeh

    Full Text Available Tamoxifen has long been used and still is the most commonly used endocrine therapy for treatment of both early and advanced estrogen receptor-positive breast cancer in pre- and post-menopause women. Tamoxifen exerts its cytotoxic effect primarily through cytostasis which is associated with the accumulation of cells in the G0/G1 phase of the cell cycle. Apoptotic activity can also be exerted by tamoxifen which involves cleavage of caspase 9, caspase 7, caspase 3, and poly-ADP-ribose polymerase (PARP. Down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulation of pro-apoptotic proteins Bax and Bak have also been observed. In addition, stress response protein of GRP 94 and GRP 78 have also been induced by tamoxifen in our study. However, side effects occur during tamoxifen treatment in breast cancer patients. Researching into combination regimen of tamoxifen and drug(s that relieves tamoxifen-induced hot flushes is important, because drug interactions may decrease tamoxifen efficacy. Risperidone has been shown to be effective in reducing or eliminating hot flushes on women with hormonal variations. In this present study, we demonstrated that combination of tamoxifen with risperidone did not interfered tamoxifen-induced cytotoxic effects in both in vitro and in vivo models, while fluoxetine abrogated the effects of tamoxifen. This is the first paper suggesting the possibility of combination treatment of tamoxifen with risperidone in breast cancer patients, providing a conceivable resolution of tamoxifen-induced side effects without interfering the efficacy of tamoxifen against breast cancer.

  14. Combination Treatment of Tamoxifen with Risperidone in Breast Cancer

    Science.gov (United States)

    Yeh, Wei-Lan; Lin, Hui-Yi; Wu, Hung-Ming; Chen, Dar-Ren

    2014-01-01

    Tamoxifen has long been used and still is the most commonly used endocrine therapy for treatment of both early and advanced estrogen receptor-positive breast cancer in pre- and post-menopause women. Tamoxifen exerts its cytotoxic effect primarily through cytostasis which is associated with the accumulation of cells in the G0/G1 phase of the cell cycle. Apoptotic activity can also be exerted by tamoxifen which involves cleavage of caspase 9, caspase 7, caspase 3, and poly-ADP-ribose polymerase (PARP). Down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulation of pro-apoptotic proteins Bax and Bak have also been observed. In addition, stress response protein of GRP 94 and GRP 78 have also been induced by tamoxifen in our study. However, side effects occur during tamoxifen treatment in breast cancer patients. Researching into combination regimen of tamoxifen and drug(s) that relieves tamoxifen-induced hot flushes is important, because drug interactions may decrease tamoxifen efficacy. Risperidone has been shown to be effective in reducing or eliminating hot flushes on women with hormonal variations. In this present study, we demonstrated that combination of tamoxifen with risperidone did not interfered tamoxifen-induced cytotoxic effects in both in vitro and in vivo models, while fluoxetine abrogated the effects of tamoxifen. This is the first paper suggesting the possibility of combination treatment of tamoxifen with risperidone in breast cancer patients, providing a conceivable resolution of tamoxifen-induced side effects without interfering the efficacy of tamoxifen against breast cancer. PMID:24886861

  15. New Techniques and Agents in the Adjuvant Therapy of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Raraty, Michael G.T.; Magee, Conor J.; Ghaneh, Paula; Neoptolemos, John P

    2002-11-01

    Pancreatic ductal adenocarcinoma represents a major oncological challenge. Despite improvements in surgical techniques, long-term survival after resection is poor, with few patients surviving after 5 years. Until recently, there have been no large randomized trials of adjuvant therapy in pancreatic ductal adenocarcinoma. However, major trials such as the European Study Group for Pancreatic Cancer (ESPAC-1) and ESPAC-3 trials have set new standards for patient recruitment and development in this field. Adjuvant therapy has the potential to improve both patient survival and quality of life after curative resection. Currently, the best treatment is with 5-fluorouracil with folinic acid, but in the light of ongoing clinical trials, this may be supplanted by gemcitabine as the treatment of choice. Chemoradiotherapy does not appear to be beneficial in the adjuvant setting, but trials of a wide variety of other techniques and agents in the treatment of advanced disease are being undertaken and some of these will almost certainly be extended into the adjuvant setting in time. Great progress has been made in the adjuvant treatment of pancreatic cancer in the past 10 years and similar advances are likely over the next decade.

  16. Endodontic treatment of teeth with periapical lesion in one session with photodynamic therapy as an adjuvant: study "in vivo"

    OpenAIRE

    Supercilio Barros Filho

    2012-01-01

    Hypothesis of the study: It is assumed that the use of photodynamic therapy (PDT) as an adjuvant in root canal therapy can promote the repair of teeth with periapical lesions treated in one session. Objectives: This in vivo study was to evaluate the effects of photodynamic therapy as an adjuvant in root canal therapy in one session for the repair of periapical lesions. Method: Fourteen human teeth with mortification pulp and periapical lesions were randomly divided into two groups (n=7): G1- ...

  17. Adjuvant Therapy for the Reduction of Postoperative Intra-abdominal Adhesion Formation

    Directory of Open Access Journals (Sweden)

    Jason PY Cheung

    2009-07-01

    Conclusions: Only a limited number of adjuvant treatment methods are currently available for the reduction of postoperative adhesions. Seprafilm has been proven to be the efficacious method to reduce adhesions. Investigations into the novel therapies are showing promising results in experimental studies and clinical studies before their wider application.

  18. Endoscopic Nd-YAG laser treatment and adjuvant therapy for metastatic lesions of airway

    International Nuclear Information System (INIS)

    Okitsu, Hiroshi; Oho, Kenkichi; Naitoh, Jun; Tajika, Eishiro; Amemiya, Ryuta; Hayata, Yoshihiro

    1989-01-01

    Endoscopic Nd-YAG laser treatment and adjuvant therapy were performed in 44 cases with metastatic lesions of airway. The best results were obtained in 31 cases (93.9%) out of 33 cases complaining of ventilatory disturbance in which endoscopic Nd-YAG laser treatment was indicated as an emergency procedure. In most of these cases with metastatic lesions of airway consisted of respiratory tract invasion from mediastinal lymph nodes in cases of esophageal cancer or lung cancer. In these cases, after laser treatment for ventilatory disturbance, the patients condition improved to the extent that adjuvant therapy could be performed. Adjuvant therapy was performed in 38 cases, there were 7 cases treated surgically (resection of the metastatic lesions of airway in 3 cases, tracheal tube stent operation in 4 cases 0, 28 radiotherapy in 28 cases (Linac irradiation in 24 cases, 60 Co intraluminal irradiation of the trachea in 4 cases 0, and 32 cases were treated with chemotherapy. Tracheal tube stent operation was useful for maintenance of the tracheal lumen following laser treatment, and 60 Co intraluminal irradiation was effective for the residual intratracheal tumor. The 1-year survival rate of 44 cases with metastatic lesions of airway was 42% and the 2-year survival rate was 22%, so this result suggested endoscopic Nd-YAG laser treatment and adjuvant therapy for metastatic lesions of airway was useful to prolong survival time. However the main value of this modality is for the rapid relief of severe ventilatory disturbance due to obstructive airway lesions. (author)

  19. Adjuvant electrochemotherapy in veterinary patients: a model for the planning of future therapies in humans

    OpenAIRE

    Spugnini, Enrico P; Citro, Gennaro; Baldi, Alfonso

    2009-01-01

    Abstract The treatment of soft tissue tumors needs the coordinated adoption of surgery with radiation therapy and eventually, chemotherapy. The radiation therapy (delivered with a linear accelerator) can be preoperative, intraoperative, or postoperative. In selected patients adjuvant brachytherapy can be adopted. The goal of these associations is to achieve tumor control while maximally preserving the normal tissues from side effects. Unfortunately, the occurrence of local and distant complic...

  20. Evaluation of Adjuvant Radiation Therapy for Resected Gallbladder Carcinoma: A Multi-institutional Experience.

    Science.gov (United States)

    Wang, Jingya; Narang, Amol K; Sugar, Elizabeth A; Luber, Brandon; Rosati, Lauren M; Hsu, Charles C; Fuller, Clifton D; Pawlik, Timothy M; Miller, Robert C; Czito, Brian G; Tuli, Richard; Crane, Christopher H; Ben-Josef, Edgar; Thomas, Charles R; Herman, Joseph M

    2015-12-01

    The role of adjuvant radiation for gallbladder carcinoma (GBC) is uncertain. We combine the experience of six National Cancer Institute-designated cancer centers to explore the impact of adjuvant radiation following oncologic resection of GBC. Patients who underwent extended surgery for GBC at Johns Hopkins, Mayo Clinic, Duke University, Oregon Health & Science University, University of Michigan, and University of Texas MD Anderson between 1985 and 2008 were reviewed. Patients with metastatic disease at surgery, gross residual disease, or missing pathologic information were excluded. Of the 112 patients identified, 61 % received adjuvant radiation, 93 % of whom received concurrent chemotherapy. Median follow-up of surviving patients was 47.3 (range 2.2-167.7) months. Patients who received adjuvant radiation had a higher rate of advanced T-stage (57 vs. 16 %, p < 0.01), lymph node involvement (63 vs. 18 %, p < 0.01), and positive microscopic margins (37 vs. 9 %, p < 0.01) compared with patients managed with surgery alone, but overall survival (OS) was comparable between the two cohorts (5-year OS: 49.7 vs. 52.5 %, p = 0.20). Lymph node involvement had the strongest association with poor OS (p < 0.01). Adjuvant radiation was associated with decreased isolated local failure (hazard ratio 0.17, 95 % confidence interval 0.05-0.63, p = 0.01). However, 71 % of recurrences included distant failure. Following oncologic resection for GBC, adjuvant radiation may offer improved local control compared with observation. The benefit of adjuvant radiation beyond chemotherapy alone should therefore be explored. Certainly, the high rate of distant failure highlights the need for more effective systemic therapy.

  1. A cost-effectiveness analysis of adjuvant therapies for resected adenocarcinoma of the rectum

    International Nuclear Information System (INIS)

    Lee, Jason H.

    1997-01-01

    PURPOSE: Several prospective randomized trials have shown a significant survival advantage with adjuvant chemotherapy and radiation therapy following surgical resection of adenocarcinoma of the rectum. Recent and ongoing trials are evaluating the role of modulated and/or protracted venous infusion [PVI] chemotherapy with pelvic irradiation [PRT]. The economic implications of additional therapies compared with their incremental benefits have not been rigorously analyzed. This study attempts to assess the incremental cost effectiveness of adjuvant therapy over surgery alone, and secondly, adjuvant therapy with PVI delivery systems versus rapid infusion. METHODS: A Markov model was constructed to describe the natural history of rectal carcinoma [stage B2, C] following surgical resection in a hypothetical cohort of 60 year old patients. This model was used to perform two sets of comparisons: [1] surgery alone versus adjuvant bolus fluorouracil [5-FU] with PRT, and [2] bolus 5-FU with PRT versus PVI 5-FU with PRT. Relapse rates and overall survival were derived from an early GITSG trial for the first comparison and from the NCCTG 86-47-51 trial for the second comparison. Medicare reimbursement rates and reports from health maintenance organizations were used to obtain net medical costs of adjuvant treatments, routine follow-up, advanced recurrent disease, and terminal illness as a result of rectal carcinoma. Total years of life and medical costs were projected over an 8-year time horizon for the first comparison [GITSG data] and over a 5-year time horizon for the second comparison [NCCTG data]. Monetary and nonmonetary benefits were discounted at 5% per year. Adjustments for quality of life, costs of adverse effects from treatment, and indirect costs of disease or treatment were not included in this current analysis. RESULTS: The main survival and economic outcomes for each treatment arm in the two comparisons are reported in the table below. For the first comparison

  2. Efficacy of systemic adjuvant therapies administered to dogs after excision of oral malignant melanomas: 151 cases (2001-2012).

    Science.gov (United States)

    Boston, Sarah E; Lu, Xiaomin; Culp, William T N; Montinaro, Vincenzo; Romanelli, Giorgio; Dudley, Robert M; Liptak, Julius M; Mestrinho, Lisa A; Buracco, Paolo

    2014-08-15

    To determine prognostic factors for and compare outcome among dogs with oral malignant melanoma following excision with or without various systemic adjuvant therapies. Retrospective case series. 151 dogs with naturally occurring oral malignant melanomas treated by excision with or without adjuvant therapies from 2001 to 2012. Case accrual was solicited from Veterinary Society of Surgical Oncology members via an email list service. Information collected from case records included signalment, tumor staging, tumor characteristics, type of surgical excision, histologic diagnosis, adjuvant therapy, and survival time. The overall median survival time was 346 days. Results of multivariate analysis indicated that tumor size, patient age, and intralesional excision (vs marginal, wide, or radical excision) were considered poor prognostic indicators. All other demographic and clinical variables were not significantly associated with survival time after adjusting for the aforementioned 3 variables. A clear survival benefit was not evident with any systemic adjuvant therapy, including vaccination against melanoma or chemotherapy; however, the number of dogs in each treatment group was small. Ninety-eight dogs received no postoperative adjuvant therapy, and there was no difference in survival time between dogs that did (335 days) and did not (352 days) receive systemic adjuvant therapy. For dogs with oral malignant melanoma, increasing tumor size and age were negative prognostic factors. Complete excision of all macroscopic tumor burden improved survival time. Long-term survival was possible following surgery alone. Although systemic adjuvant therapy was not found to improve survival time, this could have been due to type II error.

  3. An educational workshop program for rural practitioners to encourage best practice for delivery of systemic adjuvant therapy.

    Science.gov (United States)

    Dalton, Lauren; Luxford, Karen; Boyle, Fran; Goldstein, David; Underhill, Craig; Yates, Patsy

    2006-01-01

    The Rural Systemic Adjuvant Therapy Project was initiated to encourage best practice in the treatment of women from rural areas who have breast cancer. We developed an educational program, piloted it and conducted it in 5 regions. In a pre-evaluation/post-evaluation, we assessed participants' perceived knowledge about systemic adjuvant therapy. A statistically significant increase occurred in participants' reported knowledge about all program topics. Improved communication links with the local or visiting medical oncologist were planned. The workshop program was found to be a successful tool for delivering evidence-based information about the use of systemic adjuvant therapy.

  4. Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

    International Nuclear Information System (INIS)

    Condra, Kellie S.; Mendenhall, William M.; Morgan, Linda S.; Freeman, Debra E.; Marcus, Robert B.; Hagan, Michael P.

    1996-01-01

    Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

  5. Effect of adjuvant lithium on thyroxine (T4) concentration after radioactive iodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hammond, Emmanuel NiiBoye; Vangu, Mboyo-Di-Tamba Heben Willy [University of the Witwatersrand, Division of Nuclear Medicine and Molecular Imaging, Department of Radiation Sciences, Johannesburg (South Africa)

    2016-10-15

    To study the effect of adjuvant lithium on serum thyroxine (T4) concentrations in patients treated with radioactive iodine (RAI) therapy in our environment. This was a prospective simple randomized comparative, experimental cohort study of patients with hyperthyroidism referred for RAI ablation therapy in the two main academic hospitals in Johannesburg between February 2014 and September 2015. Amongst the 163 participants in the final analysis, 75 received RAI alone and 88 received RAI with lithium. The difference in mean T4 concentrations at 3 months between the RAI-only group (17.67 pmol/l) and the RAI with lithium group (11.55 pmol/l) was significant with a small effect size (U = 2328.5, Z = -2.700, p = 0.007, r = 0.01). Significant decreases in T4 concentrations were observed as early as 1 month after RAI (p = 0.0001) in the RAI with lithium group, but in the RAI-only group, significant decreases in T4 concentrations were observed only at 3 months after RAI therapy (p = 0.000). Women and patients with Graves' disease who received RAI with adjuvant lithium also showed significant decreases in T4 concentrations at 1 month (p = 0.002 and p = 0.003, respectively). Adjuvant lithium leads to an earlier and better response to RAI therapy with lower T4 concentrations that are achieved earlier. This earlier response and decrease in T4 concentrations were noted in patients with Graves' disease and nodular goitre, and in women with hyperthyroidism who received adjuvant lithium therapy. (orig.)

  6. Adjuvant Therapy for Thymic Carcinoma--A Decade of Experience in a Taiwan National Teaching Hospital.

    Directory of Open Access Journals (Sweden)

    Yen-Han Tseng

    Full Text Available Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma.To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014.Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS and overall survival (OS were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003. Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11. Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029. Among 30 patients (with stage I- IV carcinoma who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months than 2 patients who received adjuvant chemotherapy (5.9 months or 4 patients who received concurrent chemoradiotherapy (7.5 months after surgery (p = 0.003.Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection.

  7. Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

    Directory of Open Access Journals (Sweden)

    A.G.M. Mostofa

    2017-06-01

    Full Text Available Thymoquinone (TQ, the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of TQ as observed in various in vitro and in vivo animal models and discussed the pharmacological properties of TQ to rationalize its supplementary role in potentiating the efficacy of standard therapeutic modalities namely surgery, radiotherapy, chemotherapy, and immunotherapy. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical levels to delineate its implied utility as a novel complementary adjuvant therapy for cancer treatment.

  8. Oxygen carrying perfluorochemical emulsion as an adjuvant to radiation therapy

    International Nuclear Information System (INIS)

    Teicher, B.A.; Rose, C.M.

    1984-01-01

    The potential of a perfluorochemical emulsion which as an excellent carrying capacity for oxygen to enhance the ability of radiation therapy to delay the growth of Lewis lung tumor was examined. There was a highly significant effect produced by the addition of perfluorochemical emulsion and carbogen breathing in combination with irradiation. With single dose x-ray treatment the dose of perfluorochemical emulsion was varied from 0.05-0.6 ml addition to the blood volume of the animals. The dose response effect was very broad peaking at 0.3-0.4 ml which gave a dose modifying effect of 2.8 +- 0.6 with 1000 rad of x-rays. The addition of 0.3 ml of perfluorochemical free annex solution with carbogen breathing produced a small enhancement in tumor growth delay addition of the same volume of the complete emulsion increased the tumor growth delay time about 3-fold compared to the annex solution. When the perfluorochemical emulsion was added to a fractionated course of radiation therapy a dose modifying effect of 1.8 +- 0.3 was obtained. Oxygen carrying perfluorochemical emulsions may provide a nontoxic clinically useful means of increasing the effectiveness of radiation therapy and of certain chemotherapeutic agents

  9. Adjuvant Therapy for Revision Rhinoplasty of Contracted Nose Using Polydeoxyribonucleotide and Invasive Bipolar Radiofrequency

    Directory of Open Access Journals (Sweden)

    Tae Hwan Ahn, MD, PhD

    2018-01-01

    Full Text Available Summary:. Most cases of severely contracted nose require revision rhinoplasty and septoplasty, wherein preoperative and/or intraoperative expansion of nasal soft tissue is necessary for tension-free revision surgery. The present study aimed to evaluate the efficacy and safety of pre- and postoperative adjuvant therapy using polydeoxyribonucleotide (PDRN and invasive, pulsed-type, bipolar, alternating current radiofrequency (RF for revision surgery of a contracted nose. In total, 30 patients were treated with 16 sessions (8 preoperative sessions and 8 postoperative sessions of intralesional injection of PDRN and invasive RF treatment using microneedle electrodes at 1-week intervals. One week after the final combined pretreatment using PDRN and invasive bipolar RF, the skin of contracted noses was sufficiently softened, and nasal skin mobility was notably improved in all the patients. During revision rhinoplasty and septoplasty, the contracted nasal skin in each patient was adequately released for proper covering of the nasal tip without tension. Postoperatively, 8 sessions of adjuvant therapy elicited marked clinical improvements in persistent nasal tip dimpling and contracture, septal deviation, and warping from the incomplete recovery of nasal contracture after revision surgery. In conclusion, our pre- and postoperative adjuvant therapies using PDRN and invasive bipolar RF remarkably improved the therapeutic outcomes of revision rhinoplasty and septoplasty for contracted skin of the nose without major side effects.

  10. The role of adjuvant external beam radiation therapy for papillary thyroid carcinoma invading the trachea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Suk; Choi, Jae Hyuck; Kim, Kwang Sik [Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of); and others

    2017-06-15

    To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). The age range was 26–87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients.

  11. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial

    DEFF Research Database (Denmark)

    Regan, M.M.; Lykkesfeldt, A.E.; Dell'Orto, P.

    2008-01-01

    Background The Breast International Group (BIG) 1-98 trial (a randomised double-blind phase III trial) has shown that letrozole significantly improves disease-free survival (DFS) compared with tamoxifen in postmenopausal women with endocrine-responsive early breast cancer. Our aim was to establish...... over tamoxifen was noted, irrespective of ERBB2 status of the tumour, and, therefore, ERBB2 status does not seem to be a selection criterion for treatment with letrozole versus tamoxifen in postmenopausal women with endocrine-responsive early breast cancer Udgivelsesdato: 2008/1...... was the primary endpoint, and to assess treatment-by-covariate interactions. The BIG 1-98 trial is registered on the clinical trials site of the US National Cancer institute website http://www.clinicaltrials.gov/ct/show/NCT00004205. Findings By central assessment 7% (257 of 3650) of tumours were classified...

  12. Diagnostic and therapeutic approaches in Italian hospitals: adjuvant and metastatic therapy in melanoma.

    Science.gov (United States)

    Chiarion-Sileni, Vanna; Guida, Michele; Romanini, Antonella; Bernengo, Maria Grazia; Ascierto, Paolo; Queirolo, Paola; Mandalà, Mario; Maio, Michele; Ferraresi, Virginia; Stanganelli, Ignazio; Testori, Alessandro; Ridolfi, Ruggero

    2013-01-01

    Melanoma incidence and mortality rates are rising in Italy, indicating that more effective treatments are required both in the adjuvant and metastatic settings. We analyzed clinical practices in the adjuvant and metastatic settings by conducting a nationwide survey of clinicians responsible for managing melanoma treatment and follow-up in a representative sample of Italian hospitals. 95% of participating hospitals completed the panel of questions on adjuvant and metastatic treatment, making it likely that these results give a realistic picture of treatment and follow-up of melanoma patients in Italy. In low-volume hospitals (<25 new melanoma diagnoses yearly) adjuvant therapy was significantly more used than in large-volume hospitals for patients in stage III and IV (82 versus 66% and 56 versus 30%, respectively), and only 11% of patients were enrolled in clinical trials. In the metastatic setting dacarbazine was the preferred first-line treatment (32%) followed by polychemotherapy (23%); 12% of patients were enrolled in clinical trials and less than 10% received interleukin-2, usually subcutaneously. The information provided by this study was used by the Italian Melanoma Intergroup to improve the quality of care and to redirect financial resources. Copyright © 2013 S. Karger AG, Basel.

  13. Eluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital - Mayo Clinic collaborative study

    Directory of Open Access Journals (Sweden)

    Zhou Jessica

    2011-09-01

    Full Text Available Abstract Background The role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation. Methods Patients who underwent curative surgery for ampullary carcinoma at the Johns Hopkins Hospital (n = 290; 1992-2007 and at the Mayo Clinic (n = 130; 1977-2005 were reviewed. Patients with Results Median overall-survival was 39.9 months with 2- and 5-year survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic factors for overall survival included T3/T4 stage disease (RR = 1.86, p = 0.002, node positive status (RR = 3.18, p Conclusions Node-positive patients with resected ampullary adenocarcinoma may benefit from 5-FU based adjuvant chemoradiation. Since a significant proportion of patients develop metastatic disease, there is a need for more effective systemic treatment.

  14. Computational prediction of multidisciplinary team decision-making for adjuvant breast cancer drug therapies: a machine learning approach.

    Science.gov (United States)

    Lin, Frank P Y; Pokorny, Adrian; Teng, Christina; Dear, Rachel; Epstein, Richard J

    2016-12-01

    Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines. Machine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p machine learning models. A machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions regarding adjuvant chemotherapy implies that certain non-clincopathologic criteria, such as patient preference and resource availability, are factored into clinical decision-making by local experts but not captured by guidelines.

  15. Adjuvant therapy of patients with chronic dermatoses using Bedan cream

    Directory of Open Access Journals (Sweden)

    Y.F. Kutasevych

    2016-02-01

    Full Text Available The paper is devoted to the problem of treatment of chronic dermatopathies. There are demonstrated the data of study of therapeutic efficiency and tolerance of Bedan cream I patients with dermatopathies. Bedan cream used in a complex therapy of chronic dermatopathies was shown to lead to earlier reduction of objective and subjective signs of chronic dermatosis and clinical regression. It was found a good tolerance of Bedan cream: its application was not associated with deterioration of general condition of skin, its irritation and allergization.

  16. Use of propofol as adjuvant therapy in refractory delirium tremens

    Directory of Open Access Journals (Sweden)

    Rajiv Mahajan

    2010-01-01

    Full Text Available Delirium tremens is recognized as a potentially fatal and debilitating complication of alcohol withdrawal. Use of sedatives, particularly benzodiazepines, is the cornerstone of therapy for delirium tremens. But sometimes, very heavy doses of benzodiazepines are required to control delirious symptoms. We are reporting one such case of delirium tremens, which required very heavy doses of benzodiazepines and was ultimately controlled by using infusion of propofol. Thus propofol should always be considered as an option to treat patients with resistant delirium tremens.

  17. ATLAS: Adjuvant Tamoxifen Longer Against Shorter

    Science.gov (United States)

    1998-09-01

    Parma Hospital, Italy (G Cocconi, B di Blasio); Philadelphia Fox Chase G G Ribeiro, R Swindell); Coimbra Instituto de Oncologia , Portugal Cancer...van Leeuwenhoek Huis Oficina ATLAS (Espana) Inst. Portugues de Oncologia Antoninlvan Leeuwenhoek HuisCEPSS - FPT Av. Bissaia Barreto Plesmanlaan 121

  18. Adjuvant combined ozone therapy for extensive wound over tibia

    Directory of Open Access Journals (Sweden)

    Prasham Shah

    2011-01-01

    Full Text Available Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15th day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  19. Adenosarcoma of the uterus following tamoxifen treatment for breast cancer

    NARCIS (Netherlands)

    Mourits, MJE; Hollema, H; Willemse, PHB; De Vries, EGE; Aalders, JG; Van der Zee, AGJ

    1998-01-01

    A 71-year-old patient developed an uterine adenosarcoma two months after two years of tamoxifen adjuvant treatment for early breast cancer. After curettage for postmenopausal bleeding, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic

  20. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

    International Nuclear Information System (INIS)

    Pinkham, Mark B.; Foote, Matthew C.; Burmeister, Elizabeth; Thomas, Janine; Meakin, Janelle; Smithers, B. Mark; Burmeister, Bryan H.

    2013-01-01

    Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy

  1. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pinkham, Mark B., E-mail: mark.pinkham@health.qld.gov.au [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia); Foote, Matthew C. [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); Diamantina Institute, Brisbane (Australia); University of Queensland, Brisbane (Australia); Burmeister, Elizabeth [Nursing Practice Development Unit, Princess Alexandra Hospital, Brisbane (Australia); Research Centre for Clinical and Community Practice, Griffith University, Brisbane (Australia); Thomas, Janine [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); Meakin, Janelle [Clinical Trials Research Unit, Princess Alexandra Hospital, Brisbane (Australia); Smithers, B. Mark [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia); Burmeister, Bryan H. [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia)

    2013-07-15

    Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.

  2. Adjuvant therapy in patients with clear cell endometrial carcinoma: An analysis of the National Cancer Database.

    Science.gov (United States)

    Nieto, Karina; Adams, William; Pham, Nghia; Block, Alec M; Grover, Surbhi; Small, William; Harkenrider, Matthew M

    2018-01-01

    To assess the impact of adjuvant treatment, sociodemographic and tumor factors on the survival of patients with non-metastatic clear cell endometrial carcinoma (CCC). 4298 patients treated from 1998 to 2011 with Stage I-IVA CCC were identified within the National Cancer Database. FIGO 2009 staging system was used. Adjuvant groups included: hysterectomy (HYS); HYS+vaginal brachytherapy (VBT); HYS+chemotherapy (CT); HYS+external beam radiation therapy (EBRT); HYS+CT+EBRT; and HYS+CT+VBT. Univariable (UVA) and multivariable (MVA) frailty survival analyses were performed. On UVA, higher stage was associated with an increased risk of death. Compared to stage I-IA, the risk of death for stage IB was HR 1.75 (95% CI, 1.50-2.04; pgeographic education attainment (p=0.001), greater comorbidity score (p=0.001), increasing age (pNational Cancer Center Database. Given the aggressive nature of the disease, clinical trials are required to determine the optimal adjuvant therapy in patients with non-metastatic CCC to improve clinical outcomes. Published by Elsevier Inc.

  3. Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents.

    Science.gov (United States)

    Patel, Seema

    2016-01-01

    Propolis is a bee-metabolized resinous substance (bee glue) from plant sap and gums. It has been in usage as a healing agent since antiquity, yet has not garnered global popularity as a health promoter. Its biological effects, which range from antimicrobial, antioxidant, anti-inflammatory, antidiabetic, dermatoprotective, anti-allergic, laxative and immunomodulatory to anticancer, have been validated. Propolis has shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The inhibition of matrix metalloproteinases, anti-angiogenesis, prevention of metastasis, cell-cycle arrest, induction of apoptosis and moderation of the chemotherapy-induced deleterious side effects have been deduced as the key mechanisms of cancer manipulation. The components conferring antitumor potentials have been identified as caffeic acid phenethyl ester, chrysin, artepillin C, nemorosone, galangin, cardanol, etc. These compounds target various genetic and biochemical pathways of cancer progression. Depending on the botanical sources and the geographical origin, biological activities of propolis vary. Despite phenomenal development in cancer research, conventional therapy falls short in complete malignancy management. The findings obtained so far build hope that propolis as a complementary medicine may address the lacunae. This review documents the recent advances and scope of amendement in cancer remediation with adequate emphasis on the mechanistic aspect of propolis.

  4. Response to imatinib rechallenge in a patient with a recurrent gastrointestinal stromal tumor after adjuvant therapy: a case report

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    Kang Yoon-Koo

    2011-10-01

    Full Text Available Abstract Introduction Adjuvant imatinib improves recurrence-free survival of patients following resection of primary KIT-positive gastrointestinal stromal tumors. However, it is unknown whether patients who previously received adjuvant imatinib therapy will respond to imatinib rechallenge as treatment for recurrent disease. Here we present the first report documenting the benefits of imatinib rechallenge in a patient previously exposed to imatinib during adjuvant treatment. Case presentation A 51-year-old Asian woman with a wedge-resected primary gastric gastrointestinal stromal tumor at high risk of relapse underwent two years of adjuvant treatment with imatinib. Only 10 months after the completion of adjuvant imatinib treatment, a computed tomography scan revealed gastrointestinal stromal tumor recurrence in this patient, with multiple peritoneal nodules in the upper abdomen being detected. Our patient was rechallenged with imatinib 400 mg/day and had a partial response after one month of treatment. Imatinib rechallenge was well tolerated by our patient; the only adverse events she experienced were grade 1 edema, anemia and fatigue. Our patient maintained a partial response two years and six months after the imatinib rechallenge. However, computed tomography scans three months later showed that our patient had disease progression. Conclusions This case report demonstrates that a patient with a gastrointestinal stromal tumor who had previously received adjuvant imatinib therapy responded to imatinib rechallenge as treatment for her recurrent disease. These results indicate that imatinib sensitivity can be maintained in a patient with previous exposure to adjuvant imatinib therapy.

  5. Teriparatide Therapy as an Adjuvant for Tissue Engineering and Integration of Biomaterials

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    Robinder S. Dhillon

    2011-06-01

    Full Text Available Critically sized large bone defects commonly result from trauma, radical tumor resections or infections. Currently, massive allografting remain as the clinical standard to treat these critical defects. Unfortunately, allograft healing is limited by the lack of osteogenesis and bio-integration of the graft to the host bone. Based on its widely studied anabolic effects on the bone, we have proposed that teriparatide [recombinant parathyroid hormone (PTH1–34] could be an effective adjuvant for massive allograft healing. In support of this theory, here we review studies that have demonstrated that intermittent PTH1–34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms including: effects on mesenchymal stem cells (MSC, angiogenesis, chondrogenesis, bone formation and remodeling. We also review the current literature on the effects of PTH1–34 therapy on bone healing, and discuss this drug’s long term potential as an adjuvant for endogenous tissue engineering.

  6. CYP2D6 polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study

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    Wickramage I

    2017-03-01

    Full Text Available Ishani Wickramage,1 Kamani Hemamala Tennekoon,1 Merenchi Arachchige Yasantha Ariyaratne,2 Asanka Sudeshini Hewage,1 Tharmini Sundralingam,1 1Institute of Biochemistry, Molecular Biology and Biotechnology (IBMBB, University of Colombo, Colombo, Sri Lanka; 2National Cancer Institute, Maharagama, Sri Lanka Introduction and aims: Tamoxifen is an adjuvant drug effective in treating hormone ­receptor – positive breast cancer. However, 30%–50% of patients relapse and many develop adverse effects, such as hot flashes and fatty liver. Allelic variations altering the activity of cytochrome P450-2D6 enzyme affect response to tamoxifen by modulating metabolism of tamoxifen into its pharmacologically active metabolite endoxifen. Although association between CYP2D6 polymorphisms and recurrence of breast cancer in patients on tamoxifen had been reported, little evidence exists on association between these polymorphisms and adverse effects to tamoxifen. This study explored the association between CYP2D6 polymorphisms and tamoxifen effects, hitherto not studied in Sri Lanka. Methods: A retrospective preliminary study was carried out on 24 breast cancer patients on tamoxifen for minimally 3 months attending National Cancer Institute, Maharagama, Sri Lanka. They were not on CYP2D6-inhibiting drugs, chemotherapy or other endocrine therapy, and had no conditions that could occur as adverse effects to tamoxifen before starting the therapy. Their blood samples were collected, DNA was extracted and genotyped using SNaPshot Multiplex sequencing based single-nucleotide polymorphism (SNP assay. Results: SNP/allele frequencies detected: 1846G>A (confirmatory of *4 null allele=8.3%; 2549delA (confirmatory of *3 null allele=50%; 100C>T (suggestive of *10 reduced functional allele, in addition to other alleles=0%; combination of 2988G>A, -1584C and 2850C>T (strongly suggestive of *41 or other reduced functional allele=4.8%. Occurrence of heterozygous 2988G>A SNP with

  7. Enhancement of bone consolidation in mandibular distraction osteogenesis: a contemporary review of experimental studies involving adjuvant therapies.

    Science.gov (United States)

    Hong, Paul; Boyd, Daniel; Beyea, Steven D; Bezuhly, Michael

    2013-07-01

    One of the major disadvantages of mandibular distraction osteogenesis (MDO) is the prolonged time required for consolidation of the regenerate bone. The objective of the present study is to perform a contemporary review of various adjuvant therapies to enhance bone consolidation in MDO. A PubMed search for articles related to MDO, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to enhance bone consolidation. A total of 1414 titles and abstracts were initially reviewed; 61 studies were included for full review. Many studies involved growth factors, hormones, pharmacological agents, gene therapy, and stem cells. Other adjuvant therapies included mechanical stimulation, laser therapy, and hyperbaric oxygen. Majority of the studies demonstrated positive bone healing effects and thus adjuvant therapies remain a viable strategy to enhance and hasten the consolidation period. Although most studies have demonstrated promising results, many questions still remain, such as optimal amount, timing, and delivery methods required to stimulate the most favorable bone regeneration. As well, further studies comparing various adjuvant therapies and documentation of long-term adverse effects are required prior to clinical application. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy

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    Shibayama, Osamu; Yoshiuchi, Kazuhiro; Inagaki, Masatoshi; Matsuoka, Yutaka; Yoshikawa, Eisho; Sugawara, Yuriko; Akechi, Tatsuo; Wada, Noriaki; Imoto, Shigeru; Murakami, Koji; Ogawa, Asao; Akabayashi, Akira; Uchitomi, Yosuke

    2014-01-01

    Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = −2.6626 to −0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels. PMID:24756915

  9. Art therapy as an adjuvant treatment for depression in elderly women: a randomized controlled trial

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    Eliana C. Ciasca

    2018-02-01

    Full Text Available Objective: There are few quantitative studies on art therapy for the treatment of depression. The objective of this study was to evaluate if art therapy is beneficial as an adjuvant treatment for depression in the elderly. Methods: A randomized, controlled, single-blind study was carried out in a sample of elderly women with major depressive disorder (MDD stable on pharmacotherapy. The experimental group (EG was assigned to 20 weekly art therapy sessions (90 min/session. The control group (CG was not subjected to any adjuvant intervention. Patients were evaluated at baseline and after 20 weeks, using the Geriatric Depression Scale (GDS, Beck Depression Inventory (BDI, Beck Anxiety Inventory (BAI, and cognitive measures. Results: Logistic regression analysis adjusted for age revealed that women in EG (n=31 had significant improvement in GDS (p = 0.007, BDI (p = 0.025, and BAI (p = 0.032 scores as compared with controls (n=25. No difference was found in the cognitive measures. Conclusion: Art therapy as an adjunctive treatment for MDD in the elderly can improve depressive and anxiety symptoms. Clinical trial registration: RBR-2YXY7Z

  10. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy

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    Shibayama, Osamu; Yoshiuchi, Kazuhiro; Inagaki, Masatoshi; Matsuoka, Yutaka; Yoshikawa, Eisho; Sugawara, Yuriko; Akechi, Tatsuo; Wada, Noriaki; Imoto, Shigeru; Murakami, Koji; Ogawa, Asao; Akabayashi, Akira; Uchitomi, Yosuke

    2014-01-01

    Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = −2.6626 to −0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels

  11. Art therapy as an adjuvant treatment for depression in elderly women: a randomized controlled trial.

    Science.gov (United States)

    Ciasca, Eliana C; Ferreira, Rita C; Santana, Carmen L A; Forlenza, Orestes V; Dos Santos, Glenda D; Brum, Paula S; Nunes, Paula V

    2018-02-01

    There are few quantitative studies on art therapy for the treatment of depression. The objective of this study was to evaluate if art therapy is beneficial as an adjuvant treatment for depression in the elderly. A randomized, controlled, single-blind study was carried out in a sample of elderly women with major depressive disorder (MDD) stable on pharmacotherapy. The experimental group (EG) was assigned to 20 weekly art therapy sessions (90 min/session). The control group (CG) was not subjected to any adjuvant intervention. Patients were evaluated at baseline and after 20 weeks, using the Geriatric Depression Scale (GDS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and cognitive measures. Logistic regression analysis adjusted for age revealed that women in EG (n=31) had significant improvement in GDS (p = 0.007), BDI (p = 0.025), and BAI (p = 0.032) scores as compared with controls (n=25). No difference was found in the cognitive measures. Art therapy as an adjunctive treatment for MDD in the elderly can improve depressive and anxiety symptoms. RBR-2YXY7Z.

  12. Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

    Directory of Open Access Journals (Sweden)

    F.B. Silva

    2015-02-01

    Full Text Available The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF. Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23, a group that received chemotherapy + tamoxifen (n=21, and a group that received only tamoxifen (n=16. Plasma levels of NT-proBNP were assessed at 0 (T0, 6 (T6, and 12 (T12 months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

  13. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

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    Li Baoqing, E-mail: bal9018@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Margaret [Department of Surgery, Weill Cornell Medical College, New York, New York (United States); Nori, Dattatreyudu; Chao, K.S. Clifford [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Allen M. [Department of Radiation Oncology, University of California Davis Cancer Center, Sacramento, California (United States); Chen, Steven L. [Department of Surgery, University of California Davis Cancer Center, Sacramento, California (United States)

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

  14. Tamoxifen from Failed Contraceptive Pill to Best-Selling Breast Cancer Medicine: A Case-Study in Pharmaceutical Innovation.

    Science.gov (United States)

    Quirke, Viviane M

    2017-01-01

    Today, tamoxifen is one of the world's best-selling hormonal breast cancer drugs. However, it was not always so. Compound ICI 46,474 (as it was first known) was synthesized in 1962 within a project to develop a contraceptive pill in the pharmaceutical laboratories of ICI (now part of AstraZeneca). Although designed to act as an anti-estrogen, the compound stimulated, rather than suppressed ovulation in women. This, and the fact that it could not be patented in the USA, its largest potential market, meant that ICI nearly stopped the project. It was saved partly because the team's leader, Arthur Walpole, threatened to resign, and pressed on with another project: to develop tamoxifen as a treatment for breast cancer. Even then, its market appeared small, because at first it was mainly used as a palliative treatment for advanced breast cancer. An important turning point in tamoxifen's journey from orphan drug to best-selling medicine occurred in the 1980s, when clinical trials showed that it was also useful as an adjuvant to surgery and chemotherapy in the early stages of the disease. Later, trials demonstrated that it could prevent its occurrence or re-occurrence in women at high risk of breast cancer. Thus, it became the first preventive for any cancer, helping to establish the broader principles of chemoprevention, and extending the market for tamoxifen and similar drugs further still. Using tamoxifen as a case study, this paper discusses the limits of the rational approach to drug design, the role of human actors, and the series of feedback loops between bench and bedside that underpins pharmaceutical innovation. The paper also highlights the complex evaluation and management of risk that are involved in all therapies, but more especially perhaps in life-threatening and emotion-laden diseases like cancer.

  15. Survivin plays as a resistant factor against tamoxifen-induced apoptosis in human breast cancer cells.

    Science.gov (United States)

    Moriai, Ryosuke; Tsuji, Naoki; Moriai, Mikako; Kobayashi, Daisuke; Watanabe, Naoki

    2009-09-01

    Tamoxifen has been the mainstay of endocrine therapy for estrogen receptor-positive breast cancer. However, approximately 40% of breast cancer patients do not respond to tamoxifen treatment. Further, most tumors eventually acquire tamoxifen resistance. Therefore, it is necessary to develop effective modalities to enhance the efficacy of tamoxifen in breast cancer treatment. In this study, we investigated the mechanism by which breast cancer cells develop resistance against tamoxifen from the viewpoint of tamoxifen-induced apoptosis. Overexpression of the anti-apoptotic molecule survivin rendered the human breast cancer cells MCF-7 resistant to tamoxifen-induced apoptosis. To examine whether the down-regulation of survivin can enhance tamoxifen-induced apoptosis, we introduced siRNA targeting the survivin gene (survivin-siRNA) into MCF-7 cells. Survivin-siRNA transfection not only induced apoptosis without tamoxifen treatment but also augmented the tamoxifen-induced apoptosis. We have previously demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HRIs), which are widely used to reduce the serum cholesterol levels in hypercholesterolemia patients, decreases survivin expression in colon cancer cells. To develop a pharmacological approach for improving the efficacy of tamoxifen treatment, we determined whether HRIs can enhance tamoxifen-induced apoptosis. Lovastatin, an HRI, down-regulated the expression of survivin protein in MCF-7 cells in a dose-dependent manner. In addition, the proportion of apoptotic cells induced by the tamoxifen and lovastatin combination was greater than the theoretical additive effect. These results suggest that survivin may function as a factor inducing resistance against tamoxifen-induced apoptosis, and the combined use of tamoxifen and HRI may be a novel approach to overcome tamoxifen resistance in breast cancer.

  16. Clinical study of adjuvant therapy on ischemic stroke with salviae miltiorrhizae and ligustrazine

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    Jing-Qin Tian

    2017-01-01

    Full Text Available Objective: To study the effect of adjuvant therapy with salviae miltiorrhizae and ligustrazine injection on neural function injury, degree of oxidative stress reaction, chemotactic factor and adhesion molecule in patients with ischemic stroke. Methods: Patients with ischemic stroke admitted in our hospital from August 2013 to October 2015 were retrospectively analyzed and divided into conventional treatment (CT group receiving conventional treatment and traditional Chinese medicine auxiliary (TCMA group receiving adjuvant therapy with salviae miltiorrhizae and ligustrazine injection. After the treatment of the first month and the third month, serum was collected to detect the contents of nerve injury molecules, oxidative stress parameters, chemotactic factor and adhesion molecule. Results: After the 4-week treatment, the contents of serum neuron specific enolase, S100 calcium-binding protein B, heart-type fatty acid binding protein, malondialdehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine, monocyte chemoattractant protein-1, CD40, CD40 ligand, vascular endothelial cadherin, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1 in patients of TCMA group were all significantly lower than those of CT group, and the contents of superoxidase dismutase, glutathione peroxidase and catalase were significantly higher than those of CT group. After the 8-week treatment, the contents of serum neuron specific enolase, S100 calcium-binding protein B, heart-type fatty acid binding protein, malondialdehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine, monocyte chemoattractant protein-1, CD40, CD40 ligand, vascular endothelial cadherin, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1 in patients of TCMA group were all significantly lower than those of CT group and the contents of superoxidase dismutase, glutathione peroxidase and catalase were

  17. Adjuvant therapy of melanoma with interferon: lessons of the past decade

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    Kirkwood John M

    2008-10-01

    Full Text Available Abstract The effect of interferon alpha (IFNα2 given alone or in combination has been widely explored in clinical trials over the past 30 years. Despite the number of adjuvant studies that have been conducted, controversy remains in the oncology community regarding the role of this treatment. Recently an individual patient data (IPD meta-analysis at longer follow-up was reported, showing a statistically significant benefit for IFN in relation to relapse-free survival, without any difference according to dosage (p = 0.2 or duration of IFN therapy (p = 0.5. Most interestingly, there was a statistically significant benefit of IFN upon overall survival (OS that translates into an absolute benefit of at least 3% (CI 1–5% at 5 years. Thus, both the individual trials and this meta-analysis provide evidence that adjuvant IFNα2 significantly reduces the risk of relapse and mortality of high-risk melanoma, albeit with a relatively small absolute improvement in survival in the overall population. We have surveyed the international literature from the meta-analysis (2006 to summarize and assimilate current biological evidence that indicates a potent impact of this molecule upon the tumor microenvironment and STAT signaling, as well as the immunological polarization of the tumor tissue in vivo. In conclusion, we argue that there is a compelling rationale for new research upon IFN, especially in the adjuvant setting where the most pronounced effects of this agent have been discovered. These efforts have already shed light upon the immunological and proinflammatory predictors of therapeutic benefit from this agent – that may allow practitioners to determine which patients may benefit from IFN therapy, and approaches that may enable us to overcome resistance or enhance the efficacy of IFN. Future efforts may well build toward patient-oriented therapy based upon the knowledge of the unique molecular features of this disease and the immune system of each

  18. Neoadjuvant and adjuvant therapy for Stage III non-small cell lung cancer.

    Science.gov (United States)

    Watanabe, Shun-Ichi; Nakagawa, Kazuo; Suzuki, Kenji; Takamochi, Kazuya; Ito, Hiroyuki; Okami, Jiro; Aokage, Keiju; Saji, Hisashi; Yoshioka, Hiroshige; Zenke, Yoshitaka; Aoki, Tadashi; Tsutani, Yasuhiro; Okada, Morihito

    2017-12-01

    The treatments for advanced non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the 5-year survival of patients with Stage III NSCLC who underwent surgical resection alone has been dismal. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy is considered to be an appropriate treatment approach for Stage IIIA NSCLC patients; although, optimal treatment strategies are still evolving. When N2 nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy confers an overall survival benefit. The addition of postoperative radiotherapy might be considered for patients with nodal metastases. Although definitive chemoradiation remains a standard of care for cN2 NSCLC, alternative approaches such as induction chemotherapy or chemoradiotherapy and surgery can be considered for a selective group of patients. When surgical resection can be performed after induction therapy with low risk and a good chance of complete resection, the outcome may be optimal. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients.

    Science.gov (United States)

    Maithili Karpaga Selvi, N; Sridhar, M G; Swaminathan, R P; Sripradha, R

    2015-04-01

    It is known that there is a significant interplay of insulin resistance, oxidative stress, dyslipidemia, and inflammation in type 2 diabetes mellitus (T2DM). The study was undertaken to investigate the effect of turmeric as an adjuvant to anti-diabetic therapy. Sixty diabetic subjects on metformin therapy were recruited and randomized into two groups (30 each). Group I received standard metformin treatment while group II was on standard metformin therapy with turmeric (2 g) supplements for 4 weeks. The biochemical parameters were assessed at the time of recruitment for study and after 4 weeks of treatment. Turmeric supplementation in metformin treated type 2 diabetic patient significantly decreased fasting glucose (95 ± 11.4 mg/dl, P Turmeric administered group showed reduction in lipid peroxidation, MDA (0.51 ± 0.11 µmol/l, P Turmeric also exhibited beneficial effects on dyslipidemia LDL cholesterol (113.2 ± 15.3 mg/dl, P Turmeric supplementation as an adjuvant to T2DM on metformin treatment had a beneficial effect on blood glucose, oxidative stress and inflammation.

  20. Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

    Science.gov (United States)

    Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

    2017-08-01

    Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

  1. Mortality in experimental adjuvant intraoperative photodynamic therapy (AIOPDT) using ALA, Photofrin II, and mTHPC

    Science.gov (United States)

    Winkler, Steffi; Prosst, Ruediger L.; Stern, Josef; Rheinwald, Markus; Haase, Thomas; Herfarth, Christian; Gahlen, Johannes

    2001-01-01

    A clinical problem in the treatment of colorectal cancer is the high rate of local tumor recurrence. Adjuvant therapy methods are necessary to receive a better clinical outcome in minimizing local tumor relapse. Adjuvant intraoperative photodynamic therapy (AIOPDT) seems to be a promising alternative therapy in the treatment of malignant colorectal diseases. IN experimental settings the success of AIOPDT depends on the accumulation of the photosensitizer (PS) in tumor tissue and may be jeopardized by high mortality rates, due to inadequate energy doses. Our study evaluated mortality rates of nude mice after AIOPDT with ALA, Photofrin II and mTHPC using the following various light doses: ALA/Photofrin II: 100J, 50J, 25J; mTHPC: 30J, 15J, 5J generated by an Argon-Dye-laser system. There was a close correlation between laser energy applied for AIOPDT and postoperative mortality rate. Initial high mortality rates were lowered by stepwise reduction of the energy dose. Mortality rates reached a maximum 24 hours after AIOPDT in all groups.

  2. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Al-Tonbary, Youssef; Al-Haggar, Mohammad; EL-Ashry, Rasha; EL-Dakroory, Sahar; Azzam, Hanan; Fouda, Ashraf

    2009-01-01

    Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC) in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL) during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I) have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II) have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX) antioxidant enzyme, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), liver enzymes, and bone marrow picture). Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment. PMID:19960046

  3. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Youssef Al-Tonbary

    2009-01-01

    Full Text Available Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX antioxidant enzyme, malondialdehyde (MDA, tumor necrosis factor- (TNF-, liver enzymes, and bone marrow picture. Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

  4. Modern problems of treatment of Helicobacter-associated diseases in children: opportunities of adjuvant therapy

    Directory of Open Access Journals (Sweden)

    O.Yu. Belousova

    2017-03-01

    Full Text Available Background. The relevance of research is related to a significant spread of the pathology of the upper digestive tract in children, which in most cases is caused by the pathogenic effect of Helicobacter pylori (Hp. Modern eradication strategies require adjuvant therapy. The aim of the study was to evaluate the clinical effectiveness of the Lactiale symbiotic as an adjuvant therapy for eradication schemes in children of different ages with the pathology of the upper digestive canal. Materials and methods. Seventy children with Hp-associated pathology of the upper digestive tract aged 5 to 18 years were under observation. Patients were divided into 2 groups depending on the use of the symbiotic. The diagnosis was verified using fibrogastroscopy, endoscopic pH-metry, determination of Hp-infection, morphological examination. The results were statistically processed. Results. The results of using Lactiale symbiotic in patients of group 1 as an adjuvant therapy for standard pediatric Hp eradication schemes suggest the expediency and high effectiveness of such treatment. The dynamics of complaints, absence of side effects and good tolerabi-lity of drugs against the background of reception of a symbiotic were positive. The increase in eradication efficiency by 10 % compared with standard schemes corresponds to the results of other studies. The positive influence of the symbiotic on the processes of qualitative healing of ulcers and a significant increase in anti-inflammatory effect in patients of the main subgroup with peptic ulcer of the duodenum was determined. The low result of eradication, obtained in patients with functional disorders, can be considered predictable. This is evidenced by the latest conciliatory conclusions of experts: the effectiveness of eradication in patients with functional dyspepsia does not exceed 15–30 %. Conclusions. The use of the Lactiale symbio-tic as an adjuvant therapy for eradication schemes in children of different

  5. Estrogen receptor, Progesterone receptor, HER2 status and Ki67 index and responsiveness to adjuvant tamoxifen in postmenopausal high-risk breast cancer patients enrolled in the DBCG 77C trial

    DEFF Research Database (Denmark)

    Knoop, Ann; Lænkholm, Anne Vibeke; Jensen, M. B.

    2014-01-01

    BCRR and BCM in postmenopausal patients with ER positive breast cancers. The relative benefit from tamoxifen was not significantly different in luminal A and B subtypes. Funding: The Danish Breast Cancer Cooperative Group (DBCG) prepared the original protocol (DBCG 77C) and was the sponsor of the study....... Funding was not provided to the participating departments. The biomarker study was supported by grants from the Clinical Institute, Odense University. (C) 2014 Elsevier Ltd. All rights reserved....

  6. Tamoxifen induces resistance to activated protein C.

    Science.gov (United States)

    Rühl, Heiko; Schröder, Lars; Müller, Jens; Fimmers, Rolf; Sukhitashvili, Shorena; Welz, Julia; Kuhn, Walther C; Oldenburg, Johannes; Rudlowski, Christian; Pötzsch, Bernd

    2014-05-01

    The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet. Blood samples were collected prospectively from women with breast cancer before (n=25) and monthly after start of adjuvant TAM treatment (n=75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally. APC sensitivity decreased by 41% (p=0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p=0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed. This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Timing of radiotherapy in breast-conserving therapy: a large prospective cohort study of node-negative breast cancer patients without adjuvant systemic therapy

    NARCIS (Netherlands)

    Jobsen, J.J.; van der Palen, Jacobus Adrianus Maria; Baum, M.; Brinkhuis, M.; Struikmans, H.

    2013-01-01

    Background: To investigate the issue of timing of radiation therapy (RT) after lumpectomy in relation to recurrences and outcome. Methods: Analysis was done on 1107 breast-conserving therapies (BCT) with 1070 women, all without lymph node metastasis and without any adjuvant systemic therapy. Timing

  8. Impact of adjuvant therapy on recurrence patterns in stage I uterine carcinosarcoma.

    Science.gov (United States)

    Matsuo, Koji; Omatsu, Kohei; Ross, Malcolm S; Johnson, Marian S; Yunokawa, Mayu; Klobocista, Merieme M; Im, Dwight D; Bush, Stephen H; Ueda, Yutaka; Takano, Tadao; Blake, Erin A; Hasegawa, Kosei; Baba, Tsukasa; Shida, Masako; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Adachi, Sosuke; Ikeda, Yuji; Iwasaki, Keita; Miyake, Takahito M; Yanai, Shiori; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Takeuchi, Satoshi; Pejovic, Tanja; Shahzad, Mian Mk; Ueland, Frederick R; Kelley, Joseph L; Roman, Lynda D

    2017-04-01

    To examine recurrence patterns in women with stage I uterine carcinosarcoma (UCS) stratified by adjuvant therapy pattern. We examined 443 cases of stage I UCS derived from a retrospective cohort of 1192 UCS cases from 26 institutions. Adjuvant therapy patterns after primary hysterectomy-based surgery were correlated to recurrence patterns. The most common adjuvant therapy was chemotherapy alone (41.5%) followed by chemotherapy/radiotherapy (15.8%) and radiotherapy alone (8.4%). Distant-recurrence was the most common recurrence pattern (5-year cumulative rate, 28.1%) followed by local-recurrence (13.3%). On multivariate analysis, chemotherapy but not radiotherapy remained an independent prognostic factor for decreased risk of local-recurrence (5-year cumulative rates 8.7% versus 19.8%, adjusted-hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.83, P=0.01) and distant-recurrence (21.2% versus 38.0%, adjusted-HR 0.41, 95%CI 0.27-0.62, P<0.001). The chemotherapy/radiotherapy group had a lower 5-year cumulative local-recurrence rate compared to the chemotherapy alone group but it did not reach statistical significance (5.1% versus 10.1%, adjusted-HR 0.46, 95%CI 0.13-1.58, P=0.22). Radiotherapy significantly decreased local-recurrence when tumors had high-grade carcinoma, sarcoma component dominance, and deep myometrial tumor invasion (all, P<0.05); and combining radiotherapy with chemotherapy was significantly associated with decreased local-recurrence compared to chemotherapy alone in the presence of multiple risk factors (5-year cumulative rates, 2.5% versus 21.8%, HR 0.12, 95%CI 0.02-0.90; P=0.013) but not in none/single factor (P=0.36). Adjuvant chemotherapy appears to be effective to control both local- and distant-recurrences in stage I UCS; adding radiotherapy to chemotherapy may be effective to control local-recurrence when the tumor exhibits multiple risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Adherence to Needed Adjuvant Therapy Could Decrease Recurrence Rates for Rural Patients With Early Breast Cancer.

    Science.gov (United States)

    Xuan, Qijia; Gao, Kun; Song, Ying; Zhao, Shu; Dong, Lina; Zhang, Zhongbai; Zhang, Qingyuan; Wang, Jingxuan

    2016-12-01

    The purpose of this study was to evaluate the differences in stage upon diagnosis, adherence to adjuvant treatment, and recurrence between rural and urban patients with early breast cancer. This retrospective study included 3640 patients with primary breast cancer recruited from 2000 to 2009. Patients who developed recurrence or metastasis were verified by adequate diagnostic imaging modalities and pathology. The χ 2 test was used to compare groups with respect to variables (recurrence and clinicopathologic features). A multivariable Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for breast cancer recurrence risk. Compared with tumors in urban patients, those in rural patients showed higher histologic grade, larger size, more lymphatic metastasis, and higher Ki-67 index; therapy adherence was strongly associated with recurrence in both. Compared with urban patients, the female rural patients had a higher recurrence rate. However, no significant difference in recurrence rates was observed between urban and rural patients following guideline adherence. The results of our study suggest that the later stage upon diagnosis and nonadherence to treatment contribute toward worse breast cancer outcomes among rural patients with breast cancer. Adherence to needed adjuvant therapy could decrease recurrence rates for rural patients with early breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. [Value of adjuvant basic therapy in chronic recurrent skin diseases. Neurodermatitis atopica/psoriasis vulgaris].

    Science.gov (United States)

    Schöpf, E; Mueller, J M; Ostermann, T

    1995-07-01

    Atopic dermatitis and psoriasis vulgaris belong to the most common diseases in dermatology. Since these chronical diseases progress over years and decades, they may lead to restrictions in private and professional life as well as to psychological stress of concerned patients. Therefore, a lasting, stabilising, stage-adjusted topical treatment is necessary. Main component of this treatment in a complete therapeutical concept consists in an adjuvant basic therapy with oil baths and with emollients containing urea or no drug additives at all. Thus the vehicle itself is therapeutically effective. Altered structure and function of the skin measured by increased transepidermal water loss, dysfunction of skin lipid barrier, augmented skin permeability and skin roughness can be improved. Due to this treatment clinical symptoms can be diminished and relapses can be avoided. Corticosteroids and other specific medications can be reduced by using basic therapeutics with little side effects. This means economical benefit as well. So far adjuvant basic treatment is an essential part in the therapy of chronic inflammatory skin diseases.

  11. Assessment of adjuvant ademetionine therapy for the bilirubin metabolism and target organ function of neonatal jaundice

    Directory of Open Access Journals (Sweden)

    Fang Xu

    2017-11-01

    Full Text Available Objective: To study the effect of adjuvant ademetionine (SAMe therapy on the bilirubin metabolism and target organ function of neonatal jaundice. Methods: A total of 68 children who were diagnosed with neonatal jaundice in Hubei Jianghan Oilfield General Hospital between March 2015 and April 2017 were selected as the research subjects and randomly divided into the SAMe group who received ademetionine combined with blue ray irradiation and the control group who received blue ray irradiation. The serum contents of bilirubin metabolism indexes and target organ injury markers before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of both groups were lower than those before treatment, and serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of SAMe group were lower than those of control group. Conclusion: Adjuvant ademetionine therapy can improve the bilirubin metabolism of neonatal jaundice and reduce the central nerve, myocardial and liver injury.

  12. Postoperative radiation therapy and adjuvant chemoimmunotherapy in breast cancer. Aspects of timing and immune competence

    Energy Technology Data Exchange (ETDEWEB)

    Klefstroem, P.; Nuortio, L.; Taskinen, E.

    The effects of radiation therapy and adjuvant chemoimmunotherapy on the immune competence of patients with breast cancer were investigated. The tests performed included intradermal tuberculin tests, T- and B-lymphocyte counts, and lymphocyte blast transformation tests; phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PMW) were used as mitogens. Enhancement in lymphocyte proliferative response to mitogenic stimulation by PHA and PMW was seen in patients after 3 courses of chemotherapy + levamisole, whereas irradiation given after chemotherapy caused long-lasting depression in response to PHA and PWM (not significant). T-lymphocyte counts were also lower after irradiation than after chemoimmunotherapy. Clinically, the 16 patients treated with radiation therapy after chemotherapy exhibited a higher recurrence rate than the 24 patients treated first by irradiation. Enhanced reactivity to tuberculin tests occurred generally in patients receiving a planned treatment including irradiation, chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) and levamisole. Enhancement of reactivity was seen more often in patients who had not relapsed.

  13. Health promotion for young patients with haemophilia. Counselling, adjuvant exercise therapy and school sports.

    Science.gov (United States)

    Sondermann, Judith; Herbsleb, Marco; Stanek, Frank-Detlef; Gabriel, Holger; Kentouche, Karim

    2017-05-10

    The haemophilia treatment centre of the Clinic for Children and Youth Medicine in Jena extends medical care by health-promotion measures, namely: health counselling, adjuvant exercise therapy and school sports. In addition to the regular medical checks at the treatment centre patients are examined regarding physical fitness, joint situation, quality of life in general and disease-specific manner, as well as psycho-social and nutritional behaviour. Findings and medical results of the examinations are integrated into an individual advice on therapy, school sports, and health recommendations. This aimed at strengthening health-related resources and minimizing potential injuries. First long-term evaluation shows an increase of activity behaviour and physical fitness without increasing bleeding rate and maintained joint function. Combining functional prevention diagnostics and individual health counselling shows signs of improved patient's health knowledge, self-competence and physical fitness.

  14. Adjuvant electrochemotherapy in veterinary patients: a model for the planning of future therapies in humans

    Directory of Open Access Journals (Sweden)

    Baldi Alfonso

    2009-08-01

    Full Text Available Abstract The treatment of soft tissue tumors needs the coordinated adoption of surgery with radiation therapy and eventually, chemotherapy. The radiation therapy (delivered with a linear accelerator can be preoperative, intraoperative, or postoperative. In selected patients adjuvant brachytherapy can be adopted. The goal of these associations is to achieve tumor control while maximally preserving the normal tissues from side effects. Unfortunately, the occurrence of local and distant complications is still elevated. Electrochemotherapy is a novel technique that combines the administration of anticancer agents to the application of permeabilizing pulses in order to increase the uptake of antitumor molecules. While its use in humans is still confined to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, in veterinary oncology this approach is rapidly becoming a primary treatment. This review summarizes the recent progresses in preclinical oncology and their possible transfer to humans.

  15. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.

    Science.gov (United States)

    Pagani, Olivia; Regan, Meredith M; Walley, Barbara A; Fleming, Gini F; Colleoni, Marco; Láng, István; Gomez, Henry L; Tondini, Carlo; Burstein, Harold J; Perez, Edith A; Ciruelos, Eva; Stearns, Vered; Bonnefoi, Hervé R; Martino, Silvana; Geyer, Charles E; Pinotti, Graziella; Puglisi, Fabio; Crivellari, Diana; Ruhstaller, Thomas; Winer, Eric P; Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara; Giobbie-Hurder, Anita; Price, Karen N; Bernhard, Jürg; Luo, Weixiu; Ribi, Karin; Viale, Giuseppe; Coates, Alan S; Gelber, Richard D; Goldhirsch, Aron; Francis, Prudence A

    2014-07-10

    Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

  16. Acute treatment-related diarrhea during postoperative adjuvant therapy for high-risk rectal carcinoma

    International Nuclear Information System (INIS)

    Miller, Robert C.; Martenson, James A.; Sargent, Daniel J.; Kahn, Michael J.; Krook, James E.

    1998-01-01

    Purpose: The combination of pelvic radiotherapy and 5-fluorouracil-based chemotherapy is associated with an increase in acute gastrointestinal toxicity during rectal adjuvant therapy, most notably an increased incidence of diarrhea. Previous randomized, prospective studies have limited their analysis to presenting rates of severe and life-threatening diarrhea (Grade 3 or greater), and few data are available detailing the extent of mild to moderate diarrhea. To provide baseline data for future studies, we conducted a detailed analysis of diarrhea from a prior clinical trial of adjuvant therapy for rectal cancer. Methods and Materials: In a multiinstitutional clinical trial, 204 eligible patients with rectal carcinoma that either was deeply invasive (T3-T4) or involved regional lymph nodes were randomized to receive either postoperative pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherapy and bolus 5-fluorouracil-based chemotherapy. Toxicity was assessed prospectively. Results: For the 99 eligible patients who received pelvic radiotherapy alone, rates of Grades 0, 1, 2, 3, and 4 diarrhea during treatment were 59, 20, 17, 4, and 0%, respectively. For the 96 eligible patients who received radiotherapy and 5-fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34, 23, 20, and 2%, respectively. The increased rates of diarrhea during adjuvant rectal therapy were manifested across all toxicity levels for patients receiving chemotherapy and pelvic radiotherapy. Of primary clinical importance is the substantial increase in severe or life-threatening diarrhea (Grade 3 or more) (22 vs. 4%, p = 0.001) Additionally, increased rates of any diarrhea and also severe or life-threatening diarrhea were observed in patients who had a low anterior resection compared with those who had an abdominoperineal resection (p < 0.001 and p = 0.006, respectively). Conclusion: These results will be of value as a baseline for investigators who want to use

  17. Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

    International Nuclear Information System (INIS)

    Valicenti, Richard K.; Thompson, Ian; Albertsen, Peter; Davis, Brian J.; Goldenberg, S. Larry; Wolf, J. Stuart; Sartor, Oliver; Klein, Eric; Hahn, Carol; Michalski, Jeff; Roach, Mack; Faraday, Martha M.

    2013-01-01

    Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review

  18. Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Valicenti, Richard K., E-mail: Richard.valicenti@ucdmc.ucdavis.edu [Department of Radiation Oncology, University of California, Davis School of Medicine, Davis, California (United States); Thompson, Ian [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Albertsen, Peter [Division of Urology, University of Connecticut Health Center, Farmington, Connecticut (United States); Davis, Brian J. [Department of Radiation Oncology, Mayo Medical School, Rochester, Minnesota (United States); Goldenberg, S. Larry [Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia (Canada); Wolf, J. Stuart [Department of Urology, University of Michigan, Ann Arbor, Michigan (United States); Sartor, Oliver [Department of Medicine and Urology, Tulane Medical School, New Orleans, Louisiana (United States); Klein, Eric [Glickman Urological Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Hahn, Carol [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Michalski, Jeff [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Faraday, Martha M. [Four Oaks, Inc (United States)

    2013-08-01

    Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.

  19. The occurrence of fractures after adjuvant treatment of breast cancer

    DEFF Research Database (Denmark)

    Kristensen, Bent; Ejlertsen, Bent; Jensen, Maj-Britt

    2018-01-01

    BACKGROUND: Adjuvant treatment in breast cancer patients especially with aromatase inhibitors (AIs) has adverse effects on bone metabolism resulting in an increased occurrence of fractures. In order to demonstrate this occurrence, long-term follow-up studies are necessary. From several national...... registries in Denmark, it is possible to link data from different sources and analyze this issue. METHODS: A study cohort of 68,842 breast cancer patients prospectively diagnosed and registered in the Danish Breast Cancer Cooperative Group's database during the period 1995-2012 formed the basis...... menopause and tamoxifen treatment were associated with a lower occurrence and AI treatment, age and CCI were associated with a higher occurrence of fractures. CONCLUSION: Before advising adjuvant therapy with AIs fragile patients with chronic diseases should receive special attention in order to reduce...

  20. Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Guo-Shiou Liao

    2013-01-01

    Full Text Available Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy.

  1. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    International Nuclear Information System (INIS)

    Sher, David J.; Thotakura, Vijaya; Balboni, Tracy A.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen; Goguen, Laura A.; Annino, Donald J.; Tishler, Roy B.

    2011-01-01

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1–3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  2. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: dsher@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Thotakura, Vijaya [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Balboni, Tracy A. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Goguen, Laura A.; Annino, Donald J. [Department of Surgery, Division of Otolaryngology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2011-11-15

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  3. Gene expression profiling identifies FYN as an important molecule in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy

    DEFF Research Database (Denmark)

    Elias, D; (Hansen) Vever, Henriette; Lænkholm, A-V

    2015-01-01

    To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer, we performed gene array analyses and identified 366 genes with altered expression in four unique tamoxifen-resistant (TamR) cell lines vs the parental tamoxifen-sensitive MCF-7/S0.5 cell line. Most of these genes were...... functionally linked to cell proliferation, death and control of gene expression, and include FYN, PRKCA, ITPR1, DPYD, DACH1, LYN, GBP1 and PRLR. Treatment with FYN-specific small interfering RNA or a SRC family kinase inhibitor reduced cell growth of TamR cell lines while exerting no significant effect on MCF...... in primary breast tumors from two cohorts of endocrine-treated ER+ breast cancer patients, one with advanced disease (N=47) and the other with early disease (N=76), showed that in the former, plasma membrane-associated FYN expression strongly correlated with longer progression-free survival (P

  4. Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: A pilot study

    Science.gov (United States)

    Kahn, S. Anthony; Mullin, Christine M.; de Lorimier, Louis-Philippe; Burgess, Kristine E.; Risbon, Rebecca E.; Fred, Rogers M.; Drobatz, Kenneth; Clifford, Craig A.

    2013-01-01

    Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA. PMID:23997259

  5. Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies

    Directory of Open Access Journals (Sweden)

    Guadalupe Veronica Suarez

    2015-01-01

    Full Text Available Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB and human immunodeficiency virus (HIV. In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients.

  6. Thymoma size significantly affects the survival, metastasis and effectiveness of adjuvant therapies: a population based study

    Science.gov (United States)

    Bian, Dongliang; Zhou, Feng; Yang, Weiguang; Zhang, Kaixuan; Chen, Linsong; Jiang, Gening; Zhang, Peng; Wu, Chunyan; Fei, Ke; Zhang, Lei

    2018-01-01

    Background Thymoma, though a rare tumor disease, is the most common tumor of the anterior mediastinum. However, tumor size, as a critical factor, has been underestimated. Results Age, advanced tumor stage, and preoperative radiotherapy were poor prognostic factors of overall survival (OS) and disease specific survival (DSS) (P thymoma patients were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Survival based on thymoma size and other characteristics of tumors were analyzed by univariate and multivariate analysis. Correlation between thymoma size and thymoma metastatic status was contributed by logistic regression analysis. The efficiency of adjuvant therapy was analysis by stratification analysis. Conclusions Thymoma size could predict postoperative survival and guide chemotherapeutic regimens of patients. Larger tumor size indicated worse survival and higher metastatic rate. If thymoma is smaller than 90mm, traditional chemotherapy should be prohibited. While chemotherapy could be performed moderately when thymoma larger than 90 mm. PMID:29552309

  7. Selective Thrombolysis in Acute Deep Vein Thrombosis: Evaluation of Adjuvant Therapy In Vivo

    International Nuclear Information System (INIS)

    Roy, Sumit; Brosstad, Frank; Sakariassen, Kjell S.

    1999-01-01

    Purpose: To evaluate in a porcine model of acute deep vein thrombosis (DVT) the efficacy of dalteparin and antithrombin with respect to heparin for local adjuvant therapy during selective thrombolysis, and the utility of nitroglycerin and iloprost as heparin supplements. Methods: DVT was induced in both hind limbs using a previously described technique (n = 20). Thirty minutes later, the animal was heparinized (2500 IU IV), and bilateral sequestrated thrombolysis was performed using 8 mg alteplase: both external iliac veins were endoluminally occluded with Swan-Ganz catheters, and a multi-sideport infusion wire coaxially introduced through each catheter and advanced into the ipsilateral popliteal vein. In the control limbs, tissue plasminogen activator (tPA) 8 mg was injected as 0.8-ml boluses at 3-min intervals for 2 hr as a 0.25-mg/ml solution containing heparin 50 IU/ml (n 20). On the contralateral side, heparin was substituted with either dalteparin 50 IU/ml (n = 5) or antithrombin 12.5 IU/ml (n = 5), or supplemented with either nitroglycerin 0.075 mg/ml (n = 5) or iloprost (150 ng/ml) (n = 5). Blood samples were taken at predetermined intervals to measure the activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen concentration. At autopsy, the thrombus mass in the iliofemoral veins was measured, and the extent of residual thrombosis in the venous tributaries graded at four sites. Results: Bilateral thrombolysis was successfully completed in all animals. The median thrombus mass in the iliofemoral veins after thrombolysis was 0.48 g (range 0.06-1.58 g), 0.95 g (0.59-1.29 g), 0.74 g (0.52-0.96 g), and 0.29 g (0.0-0.77 g) for dalteparin, antithrombin, iloprost, and nitroglycerin respectively, as compared with 0.53 g (0.18-0.88 g) (p = 0.69), 0.97 g (0.46-1.15 g) (p = 0.69), 0.53 g (0.48-1.10 g) (p = 0.69), and 0.18 g (0.13-1.04 g) (p = 0.5) for the respective controls. Likewise, the severity of residual thrombosis in the venous

  8. Tamoxifen-induced acute pancreatitis – a case report

    Directory of Open Access Journals (Sweden)

    Rafał Czyżykowski

    2014-03-01

    Full Text Available Tamoxifen is a selective estrogen receptor modulator used for the treatment of oestrogen/progesterone receptor positive breast cancer. It has antagonistic or agonistic activity depending on the tissue location. Generally it causes mild and reversible side effects, however more serious ones including cardiovascular and thromboembolic adverse events, uterine cancer or acute pancreatitis can also occur. Tamoxifen, like oestrogens, increases the plasma level of TG and liver secretion of VLDL. Moreover, it inhibits the key enzymes of triglyceride metabolism. In this report we present a case of a 55-year-old woman with a history of a poorly controlled hypertriglyceridaemia diagnosed with breast cancer. She was treated with surgery and adjuvant chemotherapy, radiotherapy and hormonotherapy with tamoxifen. About three months after hormonal treatment, her triglyceride level increased. Five months later she developed an acute necrotic pancreatitis that required hospitalization. Her serum samples on admission were highly lipemic. An abdominal ultrasound showed no evidence of gallstones or dilation of the bile ducts. There was no history of alcohol abuse or abdominal trauma. Tamoxifen was suspected as a trigger factor for pancreatitis. After the drug withdrawal and administration of the conservative management the patient’s medical condition improved. Due to a postmenopausal status of the patient and no harmful effect on serum lipids, an adjuvant hormonotherapy with aromatase inhibitor was started.

  9. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET)

    DEFF Research Database (Denmark)

    Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A

    2016-01-01

    BACKGROUND: Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients...

  10. Tissue-Doppler assessment of cardiac left ventricular function during short-term adjuvant epirubicin therapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Sogaard, Peter; Mortensen, Christiane E

    2011-01-01

    It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure. The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast...

  11. Adjuvant androgen deprivation therapy augments cure and long-term cancer control in men with poor prognosis, nonmetastatic prostate cancer.

    NARCIS (Netherlands)

    Fleshner, N.; Keane, T.E.; Lawton, C.A.; Mulders, P.F.A.; Payne, H.; Taneja, S.S.; Morris, T.

    2008-01-01

    Historically, adjuvant androgen deprivation therapy has been viewed as a palliative treatment option for patients with poor-prognosis non-metastatic prostate cancer. In addition, guidelines from bodies such as the European Association of Urology and American Society for Clinical Oncology do not

  12. Trade-off preferences regarding adjuvant endocrine therapy among women with estrogen receptor-positive breast cancer.

    NARCIS (Netherlands)

    Wouters, H.; Maatman, G.A.; Dijk, L. van; Bouvy, M.L.; Vree, R.; Geffen, E.C.G. van; Nortier, J.W.; Stiggelbout, A.M.

    2013-01-01

    Background: There is substantial nonadherence to effective adjuvant endocrine therapy for breast cancer prevention. We therefore examined patients' trade-offs between the efficacy, side-effects, and regimen duration, and whether trade-offs predicted nonadherence. Patients and methods: Trade-offs

  13. Trade-off preferences regarding adjuvant endocrine therapy among women with estrogen receptor-positive breast cancer

    NARCIS (Netherlands)

    Wouters, H; Maatman, G A; Van Dijk, L; Bouvy, M L; Vree, R; Van Geffen, E C G; Nortier, J W; Stiggelbout, A M

    BACKGROUND: There is substantial nonadherence to effective adjuvant endocrine therapy for breast cancer prevention. We therefore examined patients' trade-offs between the efficacy, side-effects, and regimen duration, and whether trade-offs predicted nonadherence. PATIENTS AND METHODS: Trade-offs

  14. Mapping the Decision-Making Process for Adjuvant Endocrine Therapy for Breast Cancer: The Role of Decisional Resolve.

    Science.gov (United States)

    Beryl, Louise L; Rendle, Katharine A S; Halley, Meghan C; Gillespie, Katherine A; May, Suepattra G; Glover, Jennifer; Yu, Peter; Chattopadhyay, Runi; Frosch, Dominick L

    2017-01-01

    Studies show adjuvant endocrine therapy increases survival and decreases risk of breast cancer recurrence for hormone receptor-positive tumors. Yet studies also suggest that adherence rates among women taking this therapy may be as low as 50% owing largely to adverse side effects. Despite these rates, research on longitudinal patient decision making regarding this therapy is scant. We sought to map the decision-making process for women considering and initiating adjuvant endocrine therapy, paying particular attention to patterns of uncertainty and decisional change over time. A longitudinal series of semistructured interviews conducted at a multispecialty health care organization in Northern California with 35 newly diagnosed patients eligible for adjuvant endocrine therapy were analyzed. Analysis led to the identification and indexing of 3 new decision-making constructs-decisional phase, decisional direction, and decisional resolve-which were then organized using a visual matrix and examined for patterns characterizing the decision-making process. Our data reveal that most patients do not make a single, discrete decision to take or not take hormone therapy but rather traverse multiple decisional states, characterized by 1) phase, 2) direction, and 3) strength of resolve. Our analysis tracks these decisional states longitudinally using a grayscale-coded matrix. Our data show that decisional resolve wavers not just when considering therapy, as the existing concept of decisional conflict suggests, but even after initiating it, which may signal future decisions to forgo therapy. Adjuvant endocrine therapy, like other chronic care decisions, has a longer decision-making process and implementation period. Thus, theoretical, empirical, and clinical approaches should consider further exploring the new concept and measurement of decisional resolve, as it may help to improve subsequent medication adherence. © The Author(s) 2016.

  15. Curative effect of ganglioside sodium for adjuvant therapy on acute severe craniocerebral injury

    Directory of Open Access Journals (Sweden)

    Yun-Liang Deng

    2017-01-01

    Full Text Available Objective: To study the effect of adjuvant therapy of ganglioside sodium on intracranial pressure (ICP, partial pressure of brain tissue oxygen (PbtO2, nerve injury molecules, nerve protection molecules and indexes of oxidative stress in patients with acute severe craniocerebral injury. Methods: Forty-seven patients with severe craniocerebral injury treated in the emergency department of our hospital during the period time from December 2012 to October 2015 were selected for retrospective analyses. They were divided into the ganglioside group and the normal treatment group according to the usage of ganglioside sodium in the process of the emergency treatment. At days 1, 3, 5 and 7 before and after treatment, the ICP and PbtO2 in patients of the two groups were measured. After 7 days of treatment, the nerve injury molecules, nerve protection molecules and the indexes of oxidative stress in serum of the patients of the two groups were determined. Results: At days 1, 3, 5 and 7 before and after treatment, the ICP in patients of the ganglioside group were all significantly lower than those of the normal treatment group, while the PbtO2 were all significantly higher than those of normal treatment group. After 7 days of treatment, the contents of serum methane dicarboxylic aldehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine urine, S100β, glial fibrillary acidic portein, neuron specific enolase, myelin basic protein, neuroglobin and ubiquitin carboxyl-terminal hydrolase L1 in patients of the ganglioside group were notably lower than those of the normal treatment group, while the contents of superoxidase dismutase, glutathione peroxidase, catalase, nerve growth factor and brain derived neurotrophic factor were significantly higher than those of the normal treatment group. Conclusions: The adjuvant therapy of ganglioside sodium in patients with severe craniocerebral injury can effectively reduce ICP, improve PbtO2 and alleviate

  16. Timing of Radiotherapy and Outcome in Patients Receiving Adjuvant Endocrine Therapy

    International Nuclear Information System (INIS)

    Karlsson, Per; Cole, Bernard F.; Colleoni, Marco; Roncadin, Mario; Chua, Boon H.; Murray, Elizabeth; Price, Karen N.; Castiglione-Gertsch, Monica; Goldhirsch, Aron; Gruber, Guenther

    2011-01-01

    Purpose: To evaluate the association between the interval from breast-conserving surgery (BCS) to radiotherapy (RT) and the clinical outcome among patients treated with adjuvant endocrine therapy. Patients and Methods: Patient information was obtained from three International Breast Cancer Study Group trials. The analysis was restricted to 964 patients treated with BCS and adjuvant endocrine therapy. The patients were divided into two groups according to the median number of days between BCS and RT and into four groups according to the quartile of time between BCS and RT. The endpoints were the interval to local recurrence, disease-free survival, and overall survival. Proportional hazards regression analysis was used to perform comparisons after adjustment for baseline factors. Results: The median interval between BCS and RT was 77 days. RT timing was significantly associated with age, menopausal status, and estrogen receptor status. After adjustment for these factors, no significant effect of a RT delay ≤20 weeks was found. The adjusted hazard ratio for RT within 77 days vs. after 77 days was 0.94 (95% confidence interval [CI], 0.47-1.87) for the interval to local recurrence, 1.05 (95% CI, 0.82-1.34) for disease-free survival, and 1.07 (95% CI, 0.77-1.49) for overall survival. For the interval to local recurrence the adjusted hazard ratio for ≤48, 49-77, and 78-112 days was 0.90 (95% CI, 0.34-2.37), 0.86 (95% CI, 0.33-2.25), and 0.89 (95% CI, 0.33-2.41), respectively, relative to ≥113 days. Conclusion: A RT delay of ≤20 weeks was significantly associated with baseline factors such as age, menopausal status, and estrogen-receptor status. After adjustment for these factors, the timing of RT was not significantly associated with the interval to local recurrence, disease-free survival, or overall survival.

  17. Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

    International Nuclear Information System (INIS)

    Atallah, Vincent; Honore, Charles; Orbach, Daniel; Helfre, Sylvie; Ducassou, Anne; Thomas, Laurence; Levitchi, Mihai-Barbu; Mervoyer, Augustin; Naji, Salem; Dupin, Charles; Bosco-Levy, Pauline J.; Philippe-Chomette, Pascale; Kantor, Guy; Henriques de Figueiredo, Benedicte; Sunyach, Marie-Pierre; Sargos, Paul

    2016-01-01

    Purpose: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. Methods and Materials: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). Results: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). Conclusions: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT

  18. Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Atallah, Vincent [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Honore, Charles [Department of Digestive Surgery, Gustave-Roussy Institute, Paris (France); Orbach, Daniel; Helfre, Sylvie [Department of Pediatric Oncology, Curie Institute, Paris (France); Ducassou, Anne [Department of Radiation Oncology, Universitary Cancer Institute, Toulouse (France); Thomas, Laurence [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Levitchi, Mihai-Barbu [Department of Radiation Oncology, Alexis-Vautrin Center, Nancy (France); Mervoyer, Augustin [Department of Radiation Oncology, Cancerologie de l' ouest Institute, Nantes (France); Naji, Salem [Department of Radiation Oncology, Paoli-Calmette Institute, Marseille (France); Dupin, Charles [Department of Radiation Oncology, Universitary Hospital, Bordeaux (France); Bosco-Levy, Pauline J. [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Philippe-Chomette, Pascale [Department of Pediatric Surgery, University Paris 7 Denis Diderot, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris (France); Kantor, Guy; Henriques de Figueiredo, Benedicte [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Sunyach, Marie-Pierre [Department of Radiation Oncology, Leon-Berard Center, Lyon (France); Sargos, Paul, E-mail: p.sargos@bordeaux.unicancer.fr [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France)

    2016-07-15

    Purpose: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. Methods and Materials: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). Results: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). Conclusions: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT

  19. The treatment outcomes and the use of adjuvant therapies in breast cancer patients with severe co-morbidities.

    Directory of Open Access Journals (Sweden)

    Jaihong Han

    Full Text Available Studies have suggested a potential role of patient's co-morbidity in determining the survival outcomes of breast cancer. In this study, we examined the long-term oncologic outcomes in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions and analyzed the association between the co-morbidity and the use of adjuvant therapies.The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups.There were 1,792 (71.6%, 665 (26.6%, and 44 (1.8% patients in ASA I, II, and III, respectively. Total 95 (3.8% deaths and 269 (10.8% recurrences (loco-regional and distant occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of deaths (51 (2.8%, 38 (5.7% and 6 (13.6% deaths in ASA I, II and III group, respectively, p<0.001. The ASA 3 patients also showed significantly higher rate of breast cancer recurrence when compared to other groups (180 (10.0%, 80 (12.0% and 9 (20.5% in ASA I, II, and III, respectively, p = 0.041. Significantly fewer patients in the high co-morbidity group received adjuvant therapies (77 (4.3%, 44 (6.6% and 8 (18.2% in ASA I, II, and III, respectively, p<0.001. The increased recurrence of breast cancer in the high morbidity group was mostly seen in patients who did not receive adjuvant therapies. The incidence of serious adverse effect during the adjuvant therapy did not differ according to the co-morbidity conditions.In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high co-morbidity group was mostly seen in

  20. [Quality of life in primary and adjuvant veterinary radiation therapy. An owner survey].

    Science.gov (United States)

    Hill, M; Hirschberger, J; Zimmermann, K; Dörfelt, R; Reese, S; Wergin, M

    2014-01-01

    External radiation therapy has been available since 2011 for small animals at the University of Munich. The aim of the study was to evaluate the quality of life of treated pets and the satisfaction of their owners. The questionnaire was sent to the owners of all the pets (n = 91) that had undergone primary or adjuvant radiotherapy at the Clinic of Small Animal Medicine, University of Munich, since April 2011. The questionnaire was returned by 68 (74.7%) owners. According to their assessment, the quality of life improved in 41 cases (60.3%) after treatment where- as in 13 patients (19.1%) a decline was described. The majority of owners (88.2%) would have decided for repeated radiation therapy. Improvement of the animals' quality of life is related to a high satisfaction (83.8%) of the owners (p = 0.003) and their positive attitude towards radiotherapy (p = 0.027). Analyses showed that for these owners, the treatment was a worthwhile therapy despite it requiring much time and money.

  1. The effects of adjuvant therapies for sepsis on hepatic and renal function: a retrospective analysis of 108 ICU patients

    OpenAIRE

    CEYLAN, Berit Gökçe; YAVUZ, Lütfi; EROĞLU, Füsun; GÜLMEN, Şenol; TARHAN, Ömer Rıdvan; ALACA, Adnan

    2014-01-01

    As liver and kidney failure have a direct effect on mortality, morbidity, and intensive care unit (ICU) length of stay in sepsis patients, maintaining their functions or minimizing the degree of failure should be one of the most important goals of therapy. In this retrospective study we investigated the effects of recently introduced adjuvant therapies on hepatorenal functions in septic ICU patients. Materials and methods: We conducted comparative and retrospective data analysis of 108 pati...

  2. Use of Adjuvant Chemotherapy, Radiation Therapy, or Combined Modality Therapy and the Impact on Survival for Uterine Carcinosarcoma Limited to the Pelvis.

    Science.gov (United States)

    Wong, Andrew T; Lee, Yi-Chun; Schwartz, David; Lee, Anna; Shao, Meng; Han, Peter; Choi, Kwang; Schreiber, David

    2017-07-01

    Clinical outcomes for patients with uterine carcinosarcoma are poor after surgical management alone. Adjuvant therapies including chemotherapy (CT) and/or radiation therapy (RT) have been previously investigated, but the optimal management of this disease remains controversial. The purposes of this study were to analyze the patterns of use of adjuvant CT and RT and to assess the impact on survival of each of these treatment regimens using the National Cancer Data Base. The National Cancer Data Base was queried for patients given a diagnosis of uterine carcinosarcoma confined to the pelvis who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011. Patients were excluded if they survived less than 4 months after diagnosis. Data regarding CT and RT use were collected. Overall survival (OS) was analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to evaluate the effect of covariates on OS. A total of 4906 patients were included in this study. Median age was 67 years (interquartile range, 60-75 years). Median follow-up was 28.9 months (interquartile range, 15.4-52.9 months). There were 1777 patients (36.2%) who received no adjuvant treatment, 971 (19.8%) who received CT alone, 1060 (21.6%) who received RT alone, and 1098 (22.4%) who received both RT and CT. The 5-year OS for patients receiving no adjuvant therapy, adjuvant RT alone, adjuvant CT alone, and combined CT and RT were 44.9%, 47.1%, 47.5%, and 62.9%, respectively. On pairwise analysis, combined CT and RT was associated with improved survival compared with all other subgroups (P combined CT and RT (hazard ratio, 0.50; 95% confidence interval, 0.44-0.57; P Combination therapy with CT and RT was associated with significantly improved 5-year OS compared with no further therapy, RT alone, or CT alone.

  3. Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma

    International Nuclear Information System (INIS)

    Ma, Ji; Zhang, Jian; Liu, Wenchao; Guo, Yan; Chen, Suning; Zhong, Cuiping; Xue, Yan; Zhang, Yuan; Lai, Xiaofeng; Wei, Yifang; Yu, Shentong

    2014-01-01

    Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). However, many ER-positive patients are low reactive or resistant to tamoxifen. Metformin is a widely used anti-diabetic drug with noteworthy anti-cancer effects. We investigated whether metformin has the additive effects with tamoxifen in ER-positive breast cancer therapy. The efficacy of metformin alone and in combination with tamoxifen against ER-positive breast cancer was analyzed by cell survival, DNA replication activity, plate colony formation, soft-agar, flow cytometry, immunohistochemistry, and nude mice model assays. The involved signaling pathways were detected by western blot assay. When metformin was combined with tamoxifen, the concentration of tamoxifen required for growth inhibition was substantially reduced. Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells. In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Finally, two-drug combination therapy significantly inhibited tumor growth in vivo. The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer

  4. Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation.

    Directory of Open Access Journals (Sweden)

    Austin K Ederer

    Full Text Available The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i would have decreased resting endothelial function; and ii altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT on a cycle ergometer during which pulmonary V̇O2 and changes in near-infrared spectroscopy (NIRS-derived microvascular tissue oxygenation (TOI, total hemoglobin concentration ([Hb]total, and muscle deoxygenation ([HHb] ≈ fractional O2 extraction were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98. During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01 The rate of change for TOI (ΔTOIΔ/V̇O2 and [HHb] (Δ[HHb]/ΔV̇O2 relative to ΔV̇O2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively. In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V̇O2 and O2 delivery during exercise.

  5. Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)--a randomised controlled trial of exemestane versus continued tamoxifen after 2-3 years tamoxifen.

    Science.gov (United States)

    Bertelli, G; Hall, E; Ireland, E; Snowdon, C F; Jassem, J; Drosik, K; Karnicka-Mlodkowska, H; Coombes, R C; Bliss, J M

    2010-03-01

    The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen. Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the Intergroup Exemestane Study: a large trial in postmenopausal women with estrogen receptor-positive (or unknown) early breast cancer, disease free after 2-3 years of tamoxifen, randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment. The primary end point was the proportion of patients with abnormal (> or =5 mm) endometrial thickness (ET) on transvaginal ultrasound 24 months after randomisation. The analysis included 183 patients. Two years after randomisation, the proportion of patients with abnormal ET was significantly lower in the exemestane compared with tamoxifen arm (36% versus 62%, respectively; P = 0.004). This difference emerged within 6 months of switching treatment (43.5% versus 65.2%, respectively; P = 0.01) and disappeared within 12 months of treatment completion (30.8% versus 34.7%, respectively; P = 0.67). Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen.

  6. Hyperbaric Oxygen Therapy as an Adjuvant Therapy for Comprehensive Treatment of Fournier's Gangrene.

    Science.gov (United States)

    Li, Chao; Zhou, Xu; Liu, Long-Fei; Qi, Fan; Chen, Jin-Bo; Zu, Xiong-Bing

    2015-01-01

    To compare simple conventional treatment with the addition of hyperbaric oxygen therapy (HBOT) to conventional therapies in the treatment of Fournier's gangrene (FG). A retrospective study of clinical data was performed by reviewing 28 cases of FG from January 2004 to December 2013 at Xiangya Hospital, Central South University. Among them, 12 patients were treated with the conventional therapy (non-HBOT group) and the other 16 cases were combined with hyperbaric oxygen therapy besides conventional therapy (HBOT group). All patients were followed up for 2 months to assess the therapeutic effect. The analyzed data included age, Fournier gangrene severity index (FGSI) score, number of surgical debridement, indwelling drainage tube time, length of stay (LOS), effective time, and curative time. The mortality rate was lower in the HBOT group at 12.5% (2/16) compared to the non-HBOT group, which was 33.3% (4/12). The difference in the number of surgical debridement, indwelling drainage tube time, and curative time between were significantly lower in the HBOT group compared to the non-HBOT group. Our preliminary research suggests that the effect of combining hyperbaric oxygen therapy with conventional therapy offers considerable advantage in the management of Fournier's gangrene. Multicenter studies with a larger sample size are required to confirm these observations. © 2015 S. Karger AG, Basel.

  7. Brain Function, Structure, and Neurochemistry After Tamoxifen/Chemotherapy Assessed by Neuropsychologic Testing and 1H Magnetic Resonance Spectroscopy

    National Research Council Canada - National Science Library

    Ernst, Thomas

    2001-01-01

    .... Most recently, several reports have used a sensitive method (neuropsychological testing) to evaluate younger women with breast cancer after chemotherapy and hormonal modifying therapy (with tamoxifen...

  8. Traditional molecular markers and response to adjuvant endocrine or trastuzumab-based therapies.

    Science.gov (United States)

    Viale, Giuseppe; Ghioni, Mariacristina; Mastropasqua, Mauro G

    2010-11-01

    The accurate assessment of traditional molecular markers is essential to inform the choice of the adjuvant systemic treatments for patients with breast cancer. Extensive research efforts have been made to explore whether it is also possible to predict the actual response to the different therapeutic options based on the expression of these markers. Endocrine responsiveness of breast cancer has been eventually defined according to the expression of estrogen receptors in at least 1% of invasive tumor cells. The quantitative evaluation of estrogen receptors, progesterone receptors (PgR) and Ki-67 labeling index may help in selecting patients with estrogen receptor-positive and HER2-negative tumors who can be spared or may benefit from the addition of chemotherapy to endocrine therapy. Guideline recommendations for an optimal testing of estrogen receptors and PgR have been issued to assist pathologists in the accurate assessment of these markers. Progress has also been made in the identification of candidate patients to HER2-targeted therapies and in the prediction of response to trastuzumab. Traditional molecular markers play a major role in the selection of candidate patients to systemic interventions, but they are of limited value in predicting their actual response to the different treatments, especially when the markers are evaluated individually.

  9. Gait analysis in children treated by surgery followed by adjuvant therapy for posterior fossa tumors.

    Science.gov (United States)

    Fiorillo, Amedeo; Rinaldi, Manuela; Foggia, Luigi

    2010-12-01

    Children affected by posterior fossa tumors show signs and symptoms of neurological dysfunction, associated both to cancer itself and to cancer therapies. Abnormal gait and coordination difficulties are frequent presenting features. Radiation therapy represents the main adjuvant treatment for these patients. However it can produce significant neurologic injury, also manifested as gait disturbance months after treatment. We have analyzed temporo-spatial parameters of gait in sixteen children treated for posterior fossa tumors, mainly medulloblastomas. In all children we found a typical gait pattern of cerebellar ataxia. There were no significant differences between data obtained in children affected by severe neurological impairment and those having slight or even hardly recognizable physical signs. Although the number of patients studied is not large enough to allow definitive conclusions and gait analyses were performed after treatment, our results suggest that most children treated for posterior fossa tumors have gait disturbances and in some of them these are subclinical. Standard gait analysis laboratory methods can thus be a valuable tool for the careful assessment and follow-up of these patients.

  10. Clinical impact of PET/CT imaging after adjuvant therapy in patients with oral cavity squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Huan-Chun [Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Molecular Imaging Center, Taoyuan (China); Kang, Chung-Jan; Huang, Shiang-Fu; Liao, Chun-Ta [Chang Gung Memorial Hospital and Chang Gung University, Department of Otorhinolaryngology, Head and Neck Surgery, Taoyuan (China); Wang, Hung-Ming [Chang Gung Memorial Hospital and Chang Gung University, Department of Medical Oncology, Taoyuan (China); Lin, Chien-Yu [Chang Gung Memorial Hospital and Chang Gung University, Department of Radiation Oncology, Taoyuan (China); Lee, Li-Yu [Chang Gung Memorial Hospital and Chang Gung University, Department of Pathology, Taoyuan (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Molecular Imaging Center, Taoyuan (China); Chang Gung Memorial Hospital at Linkou, Department of Nuclear Medicine, Taoyuan (China)

    2017-09-15

    This single-center retrospective study of prospectively collected data was aimed at comparing the clinical outcomes of positron emission tomography/computed tomography (PET/CT) for patients with oral cavity squamous cell carcinoma (OSCC) with symptomatic recurrences identified by PET/CT imaging following adjuvant therapy (Group A) versus those of cases with asymptomatic recurrences diagnosed through periodic post-adjuvant therapy PET/CT surveillance (Group B). We also sought to establish the priority of salvage therapy in the two study groups. We identified 111 patients with advanced resected OSCC who developed recurrences following adjuvant therapy (51 in Group A and 60 in Group B). Histopathology served as the gold standard for recurrent lesions. The impact of post-adjuvant therapy PET/CT surveillance was examined with Kaplan-Meier curves and Cox proportional hazards regression models. The 2-year DSS and OS rates were marginally or significantly higher in Group B than in Group A (P = 0.073 and P = 0.025, respectively). Time-dependent ROC curve analysis demonstrated that the optimal cutoff values for time to positive PET/CT findings in relation to OS were 12 months for Group A and 9 months for Group B, respectively. Independent risk factors identified in multivariate analyses were used to devise two prognostic scoring systems for 2-year DSS and OS in each study group (all P < 0.001). Scheduled periodic PET/CT surveillance is a valuable tool for early detection of recurrent lesion(s) in asymptomatic OSCC patients who bear risk factors for disease recurrence. The presence of clinical symptoms and a short time to positive PET/CT findings were adverse prognostic factors for clinical outcome in patients with advanced OSCC. The priority of salvage therapy is discussed in each patient subgroup according to the devised prognostic scoring systems. (orig.)

  11. Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy

    DEFF Research Database (Denmark)

    Cronin-Fenton, D. P.; Damkier, P.; Lash, T. L.

    2014-01-01

    Tamoxifen reduces the rate of breast cancer recurrence by approximately a half. Tamoxifen is metabolized to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6). Tamoxifen is a substrate for ATP-binding cassette transporter proteins. We review...... is likely to be null or small, or at most moderate in subjects carrying two reduced function alleles. Future research should examine the effect of polymorphisms in genes encoding enzymes in tamoxifen's complete metabolic pathway, should comprehensively evaluate other biomarkers that affect tamoxifen...... effectiveness, such as the transport enzymes, and focus on subgroups of patients, such as premenopausal breast cancer patients, for whom tamoxifen is the only guideline endocrine therapy....

  12. The effects of population-based mammography screening starting between age 40 and 50 in the presence of adjuvant systemic therapy.

    Science.gov (United States)

    de Gelder, Rianne; Heijnsdijk, Eveline A M; Fracheboud, Jacques; Draisma, Gerrit; de Koning, Harry J

    2015-07-01

    Adjuvant systemic therapy has been shown to be effective in reducing breast cancer mortality. The additional effect of mammography screening remains uncertain, in particular for women aged 40-49 years. We therefore assessed the effects of screening starting between age 40 and 50, as compared to the effects of adjuvant systemic therapy. The use of adjuvant endocrine therapy, chemotherapy and the combination of endocrine- and chemotherapy, as well as the uptake of mammography screening in the Netherlands was modeled using micro-simulation. The effects of screening and treatment were modeled based on randomized controlled trials. The effects of adjuvant therapy, biennial screening between age 50 and 74 in the presence of adjuvant therapy, and extending the screening programme by starting at age 40 were assessed by comparing breast cancer mortality in women aged 0-100 years in scenarios with and without these interventions. In 2008, adjuvant treatment was estimated to have reduced the breast cancer mortality rate in the simulated population by 13.9%, compared to a situation without treatment. Biennial screening between age 50 and 74 further reduced the mortality rate by 15.7%. Extending screening to age 48 would lower the mortality rate by 1.0% compared to screening from age 50; 10 additional screening rounds between age 40 and 49 would reduce this rate by 5.1%. Adjuvant systemic therapy and screening reduced breast cancer mortality in similar amounts. Expanding the lower age limit of screening would further reduce breast cancer mortality. © 2014 UICC.

  13. Adjuvant Proton Beam Therapy in the Management of Thymoma: A Dosimetric Comparison and Acute Toxicities.

    Science.gov (United States)

    Parikh, Rahul R; Rhome, Ryan; Hug, Eugen; Tsai, Henry; Cahlon, Oren; Chon, Brian; Goenka, Anuj

    2016-09-01

    We evaluated the dosimetric differences between proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) for resected thymoma. We simultaneously report our early clinical experience with PBT in this cohort. We identified 4 patients with thymoma or thymic carcinoma treated at our center from 2012 to 2014 who completed adjuvant PBT to a median dose of 57.0 cobalt Gy equivalents (CGE; range, 50.4-66.6 CGE) after definitive resection. Adjuvant radiation was indicated for positive (n = 3) or close margin (n = 1). Median age was 45 (range, 32-70) years. Stages included II (n = 2), III (n = 1), and IVA (n = 1). Analogous IMRT plans were generated for each patient for comparison, and preset dosimetric endpoints were evaluated. Early toxicities were assessed according to retrospective chart review. Compared with IMRT, PBT was associated with lower mean doses to the lung (4.6 vs. 8.1 Gy; P = .02), esophagus (5.4 vs. 20.6 Gy; P = .003), and heart (6.0 vs. 10.4 Gy; P = .007). Percentages of lung, esophagus, and heart receiving radiation were consistently lower in the PBT plans over a wide range of radiation doses. There was no difference in mean breast dose (2.68 vs. 3.01 Gy; P = .37). Of the 4 patients treated with PBT, 3 patients experienced Grade 1 radiation dermatitis, and 1 patient experienced Grade 2 dermatitis, which resolved after treatment. With a median follow-up of 5.5 months, there were no additional Grade ≥ 2 acute or subacute toxicities, including radiation pneumonitis. PBT is clinically well tolerated after surgical resection of thymoma, and is associated with a significant reduction in dose to critical structures without compromising coverage of the target volume. Prospective evaluation and longer follow-up is needed to assess clinical outcomes and late toxicities. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy

    OpenAIRE

    Derzko, C.; Elliott, S.; Lam, W.

    2007-01-01

    Treatment with aromatase inhibitors for postmenopausal women with breast cancer has been shown to reduce or obviate invasive procedures such as hysteroscopy or curettage associated with tamoxifen-induced endometrial abnormalities. The side effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar to that seen with the natural events of aging. The consequences often include vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn may result in cys...

  15. Efficacy of prostaglandin E1 as adjuvant therapy for mild to moderate acute pancreatitis

    Directory of Open Access Journals (Sweden)

    JI Bai

    2016-01-01

    Full Text Available ObjectiveTo observe the clinical effect and efficacy of prostaglandin E1 (PGE1, the drug for microcirculation improvement, in the treatment of acute pancreatitis (AP. MethodsA total of 80 patients with mild-to-moderate AP who were hospitalized and treated in Second Department of Hepatobiliary and Pancreatic Surgery of the First Hospital of Jilin University from May 2014 to January 2015 were enrolled and randomized into two groups. Forty-four patients in control group received the conventional comprehensive therapy for AP, and 36 patients in experiment group received PGE1 in addition to the conventional therapy. The time to disappearance of abdominal symptoms and the time for serum and urine levels of amylase and serum levels of lipase, C-reactive protein (CRP, and procalcitonin (PCT to return to normal were compared between the two groups. The independent-samples t-test was applied for comparison of continuous data between the two groups, and the chi-square test or Fisher′s exact test was applied for comparison of categorical data between the two groups. ResultsThe two groups had significant differences in the time for serum levels of amylase and CRP and percentage of neutrophils to return to normal and hospital costs (P=0.041, 0.030, 0.012, and 0.026, respectively. PGE1 quickly relieved abdominal pain and distention, reduced the serum level of amylase, shortened the length of hospital stay, and reduced hospital costs. ConclusionPGE1 has good clinical effect and safety in the treatment of AP, and can be applied as an adjuvant drug in the comprehensive therapy for AP.

  16. An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

    Directory of Open Access Journals (Sweden)

    Felicity C. Stark

    2017-10-01

    Full Text Available Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1 compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18, significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies.

  17. Absent progesterone receptor expression in the lymph node metastases of ER-positive, HER2-negative breast cancer is associated with relapse on tamoxifen.

    Science.gov (United States)

    Snell, Cameron E; Gough, Madeline; Middleton, Kathryn; Hsieh, Michael; Furnas, Lauren; Seidl, Brenton; Gibbons, Kristen; Pyke, Christopher; Shannon, Catherine; Woodward, Natasha; Armes, Jane E

    2017-11-01

    Progesterone receptor (PR) expression is prognostic in early stage breast cancer. There are several reports of discordant expression between primary tumour and axillary lymph node (ALN) metastasis expression of oestrogen receptor (ER) and PR. We sought to determine whether expression of these biomarkers in the synchronous ALN metastases of ER positive (+), HER2 negative (-) breast cancer could provide more accurate prognostic information. The retrospective cohort included 229 patients from a single institution with ER+, HER2- breast cancer who had synchronous ALN metastatic disease (2005-2014). PR expression was correlated with relapse-free survival, and subset analysis was performed for patients who received adjuvant tamoxifen or an aromatase inhibitor. One patient had an ER+ primary tumour, which was ER- in the ALN metastasis. 27 (11.3%) were PR- in the primary tumour and 56 (23.6%) in the ALN metastasis. The predominant change was from PR+ in the primary tumour to PR- in the lymph node. Absence of PR expression in the ALN was significantly associated with relapse; however, this was not the case in the primary tumour. In a subset analysis of patients taking adjuvant endocrine therapy, poorer prognosis was limited to those with PR- metastases on tamoxifen (HR=5.203, 95% CI 1.649 to 16.416, p=0.005). No significant prognostic effect of PR- metastases in patients taking aromatase inhibitors was seen (HR=1.519, 95% CI 0.675 to 3.418, p=0.312). Evaluation of PR expression in ALN metastasis may enable prediction of patients who are less likely to benefit from adjuvant tamoxifen. This study should be replicated in other cohorts. 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/.

  18. Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

    Science.gov (United States)

    Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

    2017-07-01

    Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  19. Mitotically Active Leiomyoma of the Uterus in a Postmenopausal Breast Cancer Patient Receiving Tamoxifen

    Directory of Open Access Journals (Sweden)

    I-Feng Liu

    2006-06-01

    Conclusion: Endometrial cancer is rarely noted in breast cancer patients taking tamoxifen. Further, none have reported mitotically active leiomyoma of the uterus. From this case, endometrial proliferation and mitotically active leiomyoma of the uterus may be related to tamoxifen therapy, and should not be neglected in breast cancer patients.

  20. Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.

    Science.gov (United States)

    Toyoshima, Masafumi; Iwahashi, Hideki; Shima, Takashi; Hayasaka, Atsushi; Kudo, Takako; Makino, Hiromitsu; Igeta, Saori; Matsuura, Rui; Ishigaki, Nobuko; Akagi, Kozo; Sakurada, Junko; Suzuki, Hiroyoshi; Yoshinaga, Kosuke

    2015-02-14

    Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma. A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue. We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.

  1. Sibutramine as an adjuvant therapy in adolescents suffering from morbid obesity.

    Science.gov (United States)

    Reisler, Gad; Tauber, Tzvia; Afriat, Rachel; Bortnik, Oxana; Goldman, Michael

    2006-01-01

    The prevalence of morbid obesity is increasing rapidly. Weight reduction is very difficult using diet restriction and physical activity alone. Sibutramine has been shown to be effective and safe as an adjuvant therapy to diet restrictions. To describe our experience using sibutramine in weight reduction treatment of adolescents suffering from morbid obesity. The study group comprised 20 young persons (13 females, mean age 15 years 4 months, range 13-18 years) with morbid obesity (body mass index above the 95th percentile for age and/or > or =30 kg/m2) who were treated with sibutramine 10 mg once a day for 1 year. Mean BMI was 40 +/- 5.6 kg/m2 (range 30.1 - 49.5 kg/m2) at the beginning of treatment. Most patients showed an early weight reduction to mean BMI 39.3 +/- 4.9 and 35.9 +/- 5.7 at 3 and 6 months respectively, but stopped losing weight over the next 6 months. During the follow-up period 17 patients discontinued the treatment. The main reason for dropout was the slow rate of weight reduction after 6 months. Patients suffering from concomitant disorders (severe asthma, hypertension, sleep obstructive apnea) showed improvement after weight reduction. Adverse reactions from the treatment were transient, mild and well tolerated. Sibutramine may help in achieving weight reduction for a short period and in improving concomitant health problems, however its long-term effect is limited.

  2. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    Science.gov (United States)

    Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

  3. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism.

    Science.gov (United States)

    Allen, Bryan G; Bhatia, Sudershan K; Anderson, Carryn M; Eichenberger-Gilmore, Julie M; Sibenaller, Zita A; Mapuskar, Kranti A; Schoenfeld, Joshua D; Buatti, John M; Spitz, Douglas R; Fath, Melissa A

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2(•-)and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. © 2014 Published by Elsevier Ltd.

  4. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    Directory of Open Access Journals (Sweden)

    Bryan G. Allen

    2014-01-01

    Full Text Available Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses.

  5. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

    OpenAIRE

    Lesiuk, Teresa

    2016-01-01

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attent...

  6. Postoperative adjuvant radio(chemo)therapy for rectal cancer: an appraisal.

    Science.gov (United States)

    Scandolaro, Luciano; Cazzaniga, Luigi Franco; Bianchi, Ernestina; Cagna, Emanuela; Prina, Morena; Valli, Maria Carla; Barsacchi, Lucia; Frigerio, Milena

    2004-01-01

    Rectal cancer can be considered a broad-spectrum disease, where the surgeon, radiation oncologist and medical oncologist have a peculiar and specific place in order to work harmoniously as a good orchestra. The reality in common general hospitals is far from that of comprehensive cancer centers, particularly for postoperative approaches. The adjuvant therapy of rectal cancer is not codified worldwide, and it is strongly dependent on preoperative staging procedures, surgeon's acts and pathologist's decisions. Starting from our 10-year experience, we analyzed the various steps of postoperative approaches, defining possible decision errors, the incongruity of some attitudes, and the lack of knowledge of recent achievements of science in this disease. A total of 194 patients with advanced surgically removed rectal cancer (pT3-4 pN0-any pT pN+) treated with postoperative radio(chemo)therapy was reviewed retrospectively. Anterior resection was performed in 126, abdominoperineal resection in 48, and other surgical procedures in 20 patients. Irradiation was conducted with a single daily fraction of 1.8 Gy until 45 Gy, and chemotherapy consisted of the combination of 5-fluorouracil and folinic acid (Machover schedule): 47% of patients with positive nodes did not receive chemotherapy. Five-year overall survival was 60.6% and relapse-free survival was 55.5%. The main prognostic factors were pathological T and N stages. The principal route of progression was distant metastases. Acute toxicity was severe in 1 case (drug toxic hepatitis) and very severe in 16 patients, and late severe sequelae appeared in 13 patients. The outcome of rectal cancer patients has not changed during the last decade, and this was confirmed in our study. The improvement of radiotherapy techniques has reduced the adverse acute and late toxicity. The best postsurgical approach for pT3pN0 cancer remains unsolved, as the good chemotherapy combination and the real solution could be the application of a new

  7. Bladder Cancer Patterns of Pelvic Failure: Implications for Adjuvant Radiation Therapy

    International Nuclear Information System (INIS)

    Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Vaughn, David J.; Keefe, Stephen M.; Vapiwala, Neha; Deville, Curtiland; Bekelman, Justin E.; Tucker, Kai; Hwang, Wei-Ting; Malkowicz, S. Bruce; Christodouleas, John P.

    2013-01-01

    Purpose: Local-regional failures (LFs) after cystectomy with or without chemotherapy are common in locally advanced disease. Adjuvant radiation therapy (RT) could reduce LFs, but toxicity has discouraged its use. Modern RT techniques with improved normal tissue sparing have rekindled interest but require knowledge of pelvic failure patterns to design treatment volumes. Methods and Materials: Five-year LF rates after radical cystectomy plus pelvic node dissection with or without chemotherapy were determined for 8 pelvic sites among 442 urothelial bladder carcinoma patients. The impact of pathologic stage, margin status, nodal involvement, and extent of node dissection on failure patterns was assessed using competing risk analysis. We calculated the percentage of patients whose sites of LF would have been completely encompassed within various hypothetical clinical target volumes (CTVs) for postoperative radiation. Results: Compared with stage ≤pT2, stage ≥pT3 patients had higher 5-year LF rates in virtually all pelvic sites. Among stage ≥pT3 patients, margin status significantly altered the failure pattern whereas extent of node dissection and nodal positivity did not. In stage ≥pT3 patients with negative margins, failure occurred predominantly in the iliac/obturator nodes and uncommonly in the cystectomy bed and/or presacral nodes. Of these patients in whom failure subsequently occurred, 76% would have had all LF sites encompassed within CTVs covering only the iliac/obturator nodes. In stage ≥pT3 with positive margins, cystectomy bed and/or presacral nodal failures increased significantly. Only 57% of such patients had all LF sites within CTVs limited to the iliac/obturator nodes, but including the cystectomy bed and presacral nodes in the CTV when margins were positive increased the percentage of LFs encompassed to 91%. Conclusions: Patterns of failure within the pelvis are summarized to facilitate design of adjuvant RT protocols. These data suggest that

  8. Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Jin-Hyeok Hwang

    2010-05-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52 showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR for death (HR = 0.316; 95%CI = 0.166-0.600; P = 0.0004 and recurrence (HR = 0.521; 95%CI = 0.280-0.967; P = 0.04. MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC.

  9. Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

    International Nuclear Information System (INIS)

    Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.; Simeone, Diane; Greenson, Joel K.; Francis, Isaac R.; Hampton, Janet; Colletti, Lisa; Chang, Alfred E.; Lawrence, Theodore S.; Zalupski, Mark M.

    2009-01-01

    Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m 2 intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m 2 intravenously on Days 1 and 8 or capecitabine 1500 mg/m 2 orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m 2 orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of ≥180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

  10. Limited Advantages of Intensity-Modulated Radiotherapy Over 3D Conformal Radiation Therapy in the Adjuvant Management of Gastric Cancer

    International Nuclear Information System (INIS)

    Alani, Shlomo; Soyfer, Viacheslav; Strauss, Natan; Schifter, Dan; Corn, Benjamin W.

    2009-01-01

    Purpose: Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. Methods and Materials: Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 deg., 53 deg., 107 deg., 158 deg., 204 deg., 255 deg., and 306 deg.. Beam arrangement 2 consisted of gantry angles of 30 deg., 90 deg., 315 deg., and 345 deg.; a gantry angle of 320 deg./couch, 30 deg.; and a gantry angle of 35 o /couch, 312 o . Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. Results: Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. Conclusions: IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

  11. Limited advantages of intensity-modulated radiotherapy over 3D conformal radiation therapy in the adjuvant management of gastric cancer.

    Science.gov (United States)

    Alani, Shlomo; Soyfer, Viacheslav; Strauss, Natan; Schifter, Dan; Corn, Benjamin W

    2009-06-01

    Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 degrees , 53 degrees , 107 degrees , 158 degrees , 204 degrees , 255 degrees , and 306 degrees . Beam arrangement 2 consisted of gantry angles of 30 degrees , 90 degrees , 315 degrees , and 345 degrees ; a gantry angle of 320 degrees /couch, 30 degrees ; and a gantry angle of 35 degrees /couch, 312 degrees . Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

  12. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    K.-A. Phillips (Kelly-Anne); R.L. Milne (Roger); M.A. Rookus (Matti); M.J. Daly (Mark); A.C. Antoniou (Antonis C.); S. Peock (Susan); D. Frost (Debra); D.F. Easton (Douglas); S.D. Ellis (Steve); M. Friedlander (Michael); S.S. Buys (Saundra); N. Andrieu (Nadine); C. Nogues (Catherine); D. Stoppa-Lyonnet (Dominique); V. Bonadona (Valérie); P. Pujol (Pascal); S.-A. McLachlan (Sue-Anne); E.M. John (Esther); M.J. Hooning (Maartje); C.M. Seynaeve (Caroline); R.A.E.M. Tollenaar (Rob); D. Goldgar (David); M.B. Terry (Mary Beth); T. Caldes (Trinidad); P.C. Weideman (Prue C.); I.L. Andrulis (Irene); C.F. Singer (Christian); K. Birch (Kate); J. Simard (Jacques); M.C. Southey (Melissa); H.L. Olsson (Håkan L.); A. Jakubowska (Anna); E. Olah; A-M. Gerdes (Anne-Marie); L. Foretova (Lenka); J.L. Hopper (John)

    2013-01-01

    textabstractPurpose To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Methods Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up

  13. Prognostic Factors and Patterns of Locoregional Failure After Surgical Resection in Patients With Cholangiocarcinoma Without Adjuvant Radiation Therapy: Optimal Field Design for Adjuvant Radiation Therapy.

    Science.gov (United States)

    Ghiassi-Nejad, Zahra; Tarchi, Paola; Moshier, Erin; Ru, Meng; Tabrizian, Parissa; Schwartz, Myron; Buckstein, Michael

    2017-11-15

    To identify prognostic factors and patterns of local failure in patients with cholangiocarcinoma (CCA), after surgical resection in the absence of adjuvant radiation, for optimal definition of target volumes encompassing the majority of local recurrences. A chart review was performed in patients who underwent resection for primary CCA (intrahepatic, hilar, and distal) between 1999 and 2014. Local failure was defined as recurrence in a theoretical reasonable postoperative radiation volume. This includes the cut surface of liver, biliary anastomosis, hilum, portal nodes, celiac nodes, peri-pancreatic nodes, gastro-hepatic nodes, and retroperitoneal nodes. Patients who received adjuvant radiation were excluded. A total of 189 patients underwent surgical resection for CCA, of whom 145 patients had sufficient follow-up. Median follow-up was 41.6 months (95% confidence interval 35.4-48.7 months). Of the 145 cases, 102 were intrahepatic and 43 were hilar/distal CCA. Adjuvant chemotherapy was given in 38 cases (26%), of which 20 (54%) were gemcitabine-based. Eighty-six patients (59%) had a documented recurrence, of whom 44 (51%) had a locoregional component. Among patients who had a recurrence, 23 (27%) had a recurrence at the biliary anastomosis and/or cut liver surface. Twenty-eight patients (32.6%) had a recurrence in the regional lymph nodes, most prevalent in the portal (16.3%) and retroperitoneal (17.4%) lymph nodes. Univariable analysis identified tumor size, any vascular invasion, presence of satellites, stage/nodal status, and receipt of chemotherapy as significant prognostic factors of overall recurrence among intrahepatic patients. Presence of satellites, and stage 3/Nx status remained statistically significant in multivariable modeling. The areas at highest risk for locoregional recurrence after surgical resection for primary CCA are the biliary anastomosis/cut liver surface, portal lymph nodes, and retroperitoneal lymph nodes. Although these results need to

  14. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

    International Nuclear Information System (INIS)

    Sabolch, Aaron; Else, Tobias; Griffith, Kent A.; Ben-Josef, Edgar; Williams, Andrew; Miller, Barbra S.; Worden, Francis; Hammer, Gary D.; Jolly, Shruti

    2015-01-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed

  15. Effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Li Lei

    2017-11-01

    Full Text Available Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart failure who were treated in the hospital between March 2014 and March 2017 were divided into control group and levosimendan group by random number table, each with 50 cases. Control group received clinical routine therapy for chronic heart failure, and levosimendan group received routine therapy combined with adjuvant levosimendan therapy. The differences in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes were compared between the two groups before and after treatment. Results: At T0, there was no statistically significant difference in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes between the two groups. At T1, serum RAAS indexes PRA, AngⅡ and ALD levels of levosimendan group were lower than those of control group; serum thyroid hormones TT3, TT4, FT3 and FT4 levels of levosimendan group were higher than those of control group; serum myocardial damage indexes cTnⅠ, H-FABP and NT-proBNP levels of levosimendan group were lower than those of control group; serum endothelial function index NO level of levosimendan group was higher than that of control group while ET-1 level was lower than that of control group. Conclusion: Adjuvant levosimendan therapy for elderly patients with chronic heart failure can effectively adjust the secretion of neuroendocrine hormones and reduce the myocardial and vascular endothelial damage.

  16. Effect of salvianolate injection adjuvant therapy on patients with cerebral infarction

    Directory of Open Access Journals (Sweden)

    Hong-Mei Liu

    2016-03-01

    Full Text Available Objective: To discuss the effect of salvianolate injection on related indexes of patients with cerebral infarction. Methods: 84 cases of patients with cerebral infarction from October 2013 to October 2014 were selected and all patients suffered from thrombosis cerebral infarction. All patients were divided into control group and study group according to digital table method (n=42. Patients in control group were given individualized treatment, like nutrition, encephaledema elimination, thrombolytic treatment, according to their staging and individual actual situations. On the basis of control group, patients in study group were given salvianolate injection treatment. Endothelin-1 (ET-1, thrombomodulin (TM, blood platelet count, TXB2, 6-ketone-PGF1 α, antithrombin-Ⅲ (AT-Ⅲ, protein C, protein S, coagulation time, APTT , fibrinolysis activity: plasminogen activity loss: t-PA and PAI, plasma viscosity (ηb in both groups before and after treatment were compared. Results: 2 weeks after treatment, ET-1, TM, blood platelet count, TXB2, PAI-1, η b, whole blood viscosity in both groups were decreased, and compared with before treatment, difference had statistical significance (P<0.05; while 6-ketone-PGF1 α, coagulation time, APTT, antithrombin-Ⅲ, protein C, protein S, plasma t-PA in both groups were increased, and compared with before treatment, difference had statistical significance (P<0.05. After treatment, ET-1, TM, TXB2, η b in study group were obviously lower than that in control group, and comparison between groups had statistical significance (P<0.05, 6-ketone-PGF1α, antithrombin-Ⅲ, protein C, t-PA in study group were obviously higher than that in control group, and comparison between groups had statistical significance (P<0.05. Conclusions: Salvianolate injection adjuvant therapy in patients with thrombosis cerebral infarction could improve the related indexes of thrombus and had positive significance to the follow-up recovery of

  17. Provider perspectives on patient-provider communication for adjuvant endocrine therapy symptom management.

    Science.gov (United States)

    Turner, Kea; Samuel, Cleo A; Donovan, Heidi As; Beckjord, Ellen; Cardy, Alexandra; Dew, Mary Amanda; van Londen, G J

    2017-04-01

    Providers' communication skills play a key role in encouraging breast cancer survivors to report symptoms and adhere to long-term treatments such as adjuvant endocrine therapy (AET). The purpose of this study was to examine provider perspectives on patient-provider communication regarding AET symptom management and to explore whether provider perspectives vary across the multi-disciplinary team of providers involved in survivorship care. We conducted three one-hour focus groups with a multi-disciplinary group of health care providers including oncology specialists, primary care physicians, and non-physician providers experienced in caring for breast cancer survivors undergoing AET (n = 13). Themes were organized using Epstein and Street's (2007) Framework for Patient-Centered Communication in Cancer Care. The findings of this study suggest providers' communication behaviors including managing survivors' uncertainty, responding to survivors' emotions, exchanging information, and enabling self-management influences the quality of patient-provider communication about AET symptoms. Additionally, lack of systematic symptom assessment tools for AET requires providers to use discretion in determining which symptoms to discuss with survivors resulting in approaches that vary based on providers' discipline. There may be AET-specific provider communication skills and behaviors that promote effective patient-provider communication but additional research is needed to identify practices and policies that encourage these skills and behaviors among the many providers involved in survivorship care. Efforts are also needed to coordinate AET symptom assessment across providers, clarify providers' roles in symptom assessment, and determine best practices for AET symptom communication.

  18. Radiofrequency ablation of hepatic tumors: increased tumor destruction with adjuvant liposomal doxorubicin therapy.

    Science.gov (United States)

    Goldberg, S Nahum; Kamel, Ihab R; Kruskal, Jonathan B; Reynolds, Kevin; Monsky, Wayne L; Stuart, Keith E; Ahmed, Muneeb; Raptopoulos, Vassilos

    2002-07-01

    The purpose of this study was to determine whether the administration of liposomal doxorubicin before radiofrequency ablation increases coagulation more than radiofrequency alone in focal hepatic tumors. Fourteen focal hepatic tumors (diameter: mean +/- SD, 4.0+/-1.8 cm) in 10 patients (colorectal cancer, n = 3 patients; hepatocellular carcinoma, n = 4; neuroendocrine tumor, n = 2; breast cancer, n = 1) were treated with internally cooled radiofrequency ablation. In addition to undergoing radiofrequency, five patients (n = 7 lesions) were randomly assigned to receive 20 mg of IV doxorubicin in a long-circulating stealth liposome carrier (Doxil) 24 hr before ablation. Contrast-enhanced helical CT was performed immediately (within 30 min) after radiofrequency ablation (baseline) and 2-4 weeks after ablation. The volume of induced coagulation was measured by three-dimensional reconstruction techniques, and the measurements were compared. For tumors treated with radiofrequency alone, the volume of the thermal lesion had decreased 12-24% (mean +/- SD, 82.5% +/- 4.4% of initial volume) at 2-4 weeks after ablation. By comparison, increased tumor destruction at 2-4 weeks after ablation was observed for all lesions treated with combined Doxil and radiofrequency (p<0.001). Six lesions increased 24-36% in volume, and coagulation surrounding a small colorectal metastasis increased 342%. No coagulation was identified in four unablated control lesions in the two patients receiving Doxil alone. Our pilot clinical study suggests that adjuvant Doxil chemotherapy increases tumor destruction compared with radiofrequency ablation therapy alone in a variety of focal hepatic tumors. Optimization of this synergistic strategy may ultimately allow improved clinical efficacy and outcome.

  19. Familial prostate cancer: outcome following radiation therapy with or without adjuvant androgen ablation

    International Nuclear Information System (INIS)

    Hanus, Michael C.; Zagars, Gunar K.; Pollack, Alan

    1999-01-01

    Purpose: To compare the outcome of familial versus sporadic prostate carcinoma after definitive external radiation. Methods and Materials: Between 1987 and 1996, 1214 men with clinically localized prostate cancer (T1-T4, N0/NX, M0) received definitive radiation therapy in our department. By retrospective review of charts and questioning of patients, a record on the presence or absence of prostate cancer in a first degree relative was obtained in 1164 men. Univariate and multivariate analysis was performed on these cases with relapse or rising prostate-specific antigen (PSA), local recurrence, metastasis, and survival as endpoints. Results: Familiar prostate cancer was present in 148 of 1164 men (13%). Men with familial disease were slightly but significantly younger (mean 66 years) at diagnosis than those with sporadic disease (mean 68 years) (p = 0.02). Apart from this there were no significant differences between the two groups in T-stage, Gleason score, pretreatment PSA levels, DNA ploidy, or serum testosterone levels. There were no significant differences in treatment parameters including radiation dose and the use of adjuvant androgen ablation. With a median follow-up of 42 months, there was no difference in freedom from relapse or rising PSA at 6 years between those with a family history (54%) and those without a family history (58%) (p = 0.171). Likewise there was no difference between the two groups when local recurrence or metastasis was the endpoint. Multiple subgroup analyses (younger and older; T1/T2 and T3; low Gleason and high Gleason; no androgen ablation and androgen ablation; race) failed to reveal any differences in outcome in any category between familial and sporadic disease. Among patients with a rising post-treatment PSA profile, PSA doubling times were similar in those with sporadic and familial disease. Conclusions: This study provides no evidence for any substantial difference between familial and sporadic prostate cancer either in

  20. Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

    International Nuclear Information System (INIS)

    Higgins, Kristin A.; Chino, Junzo P.; Berry, Mark; Ready, Neal; Boyd, Jessamy; Yoo, David S.; Kelsey, Chris R.

    2012-01-01

    Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non–small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non–small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995–2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meier method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.

  1. Adjuvant therapy in the treatment of gallbladder cancer: a meta-analysis

    International Nuclear Information System (INIS)

    Ma, Ning; Cheng, Hui; Qin, Baodong; Zhong, Renqian; Wang, Bin

    2015-01-01

    The benefit of adjuvant therapy (AT) for gallbladder cancer (GBC) is unclear as evidenced by conflicting results from nonrandomized studies. Here we aimed to perform a meta-analysis to determine the impact of AT on overall survival (OS). We used data from MEDLINE, EMBASE and the Cochrane Collaboration Library and published between October 1967 and October 2014. Studies that evaluated AT compared with curative-intent surgery alone for resected GBC were included. Subgroup analyses of benefit based on node status, margins status, and American Joint Committee on Cancer (AJCC) staging were prespecified. Data were weighted and pooled using random-effect modeling. Ten retrospective studies involving 3,191 patients were analyzed. There was a nonsignificant improvement in OS with AT compared with surgery alone (hazard ratio [HR], 0.76; 95 % confidence interval [CI], 0.56–1.03). A significant improvement was observed in OS with chemotherapy (CT) compared with surgery alone (HR, 0.42; 95 % CI, 0.22–0.80) by sensitivity analysis. The greatest benefit for AT was also observed in those with R1 disease (HR, 0.33; 95 % CI, 0.19–0.59), LN-positive disease (HR, 0.71; 95 % CI, 0.63–0.81), and AJCC staging meeting or exceeding tumor Stage II (HR, 0.45; 95 % CI, 0.26–0.79), but not in those with LN-negative or R0 disease. Our results strongly support the use of CT as an AT in GBC. Moreover, patients with node positivity, margin positivity, or non-stage I disease are more likely to benefit from AT

  2. The iBRA-2 (immediate breast reconstruction and adjuvant therapy audit) study: protocol for a prospective national multicentre cohort study to evaluate the impact of immediate breast reconstruction on the delivery of adjuvant therapy.

    Science.gov (United States)

    Dave, Rajiv; O'Connell, Rachel; Rattay, Tim; Tolkien, Zoe; Barnes, Nicola; Skillman, Joanna; Williamson, Paula; Conroy, Elizabeth; Gardiner, Matthew; Harnett, Adrian; O'Brien, Ciara; Blazeby, Jane; Potter, Shelley; Holcombe, Chris

    2016-10-07

    Immediate breast reconstruction (IBR) is routinely offered to improve quality of life for women with breast cancer requiring a mastectomy, but there are concerns that more complex surgery may delay the delivery of adjuvant oncological treatments and compromise long-term oncological outcomes. High-quality evidence, however, is lacking. iBRA-2 is a national prospective multicentre cohort study that aims to investigate the effect of IBR on the delivery of adjuvant therapy. Breast and plastic surgery centres in the UK performing mastectomy with or without (±) IBR will be invited to participate in the study through the trainee research collaborative network. All women undergoing mastectomy ± IBR for breast cancer between 1 July and 31 December 2016 will be included. Patient demographics, operative, oncological and complication data will be collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR will be compared to determine the impact that IBR has on the time of delivery of adjuvant therapy. Prospective data on 3000 patients from ∼50 centres are anticipated. Research ethics approval is not required for this study. This has been confirmed using the online Health Research Authority decision tool. This novel study will explore whether IBR impacts the time to delivery of adjuvant therapy. The study will provide valuable information to help patients and surgeons make more informed decisions about their surgical options. Dissemination of the study protocol will be via the Mammary Fold Academic and Research Collaborative (MFAC) and the Reconstructive Surgery Trials Network (RSTN), the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS). Participating units will have access to their own data and collective results will be presented at relevant surgical conferences and published in appropriate peer-reviewed journals. Published by

  3. ROLE OF MORPHOLOGICAL AND GENETIC STRUCTURAL CHARACTERISTICS OF ESTROGEN RECEPTOR ALPHA IN THE DEVELOPMENT OF RESISTANCE TO ENDOCRINOTHERAPY WITH TAMOXIFEN IN PATIENTS WITH LUMINAL BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Е. М. Slonimskaya

    2014-01-01

    Full Text Available Hormone therapy with tamoxifen is the commonly used treatment for luminal breast cancer. However, it appears to be ineffective in 20–40 % of cases and the possible reasons of this failure are related to the features of distribution and structure of estrogen receptor alpha (ERα in tumor tissue. Realization of the therapeutic effect of tamoxifen is carried out by blocking the activation center of AF-2 receptor. The change in the functional state of this receptor resulted from single-nucleotide polymorphisms coding 2228480 (G/A in exon 8 of ERα gene is considered as a possible cause of treatment failure with tamoxifen.The purpose of the study was to analyze the relationship between the ERα expression and polymorphic variants in exon 8 of the ERα gene and the efficacy of tamoxifen in patientswith luminal breast cancer.Material and methods: The study included 97 patients with stage T1–2N0–1M0 luminal breast cancer, who received adjuvant chemotherapy with tamoxifen. The follow-up ranged from 24 to 130 months. Long-term treatment outcomes were assessed upon the progression of the disease with the evidence of distant metastases. In tumor tissue samples, the ERα expression was studied using the immunohistochemical method. The values of the ERα expression intensity as well as the character of ERα distribution were assessed. Polymorphic variants of exon 8 of the ERα gene were studied using real-time PCR.Results. The heterogeneous distribution of ERα gene was observed in 86.5 % cases with diseases progression and in 58.3 % of cases with favorable disease outcome (р=0.0072; χ2 =7.22. Mutation of rs2228480 (G/A in exon 8 of the ERα gene was observed in 19.4 % of cases. Mutations were not noted in tumor cells with homogenous distribution of the ERα gene and mutations were found in 25.7 % (р=0.014; χ2 =6.09 in heterogeneous distribution. Mutation in exon 8 of the ERα gene was shown to occur more often in patients with disease progression

  4. Evaluation of adverse effects in tamoxifen exposed healthy female dogs.

    Science.gov (United States)

    Tavares, Wanessa L F; Lavalle, Gleidice E; Figueiredo, Mariana S; Souza, Aline G; Bertagnolli, Angelica C; Viana, Fernando A B; Paes, Paulo R O; Carneiro, Rubens A; Cavalcanti, Guilherme A O; Melo, Marilia M; Cassali, Geovanni D

    2010-12-22

    Mammary tumors are among the most frequent neoplasms in female dogs, but the strategies employed in animal treatment are limited. In human medicine, hormone manipulation is used in cancer therapy. Tamoxifen citrate is a selective inhibitor of oestrogen receptors and exerts a potent anti-oestrogen effect on the mammary gland. The aim of this study was to evaluate the adverse effects when exposing healthy female dogs to tamoxifen. Tamoxifen was administered for 120 days at a dose of 0.5 or 0.8 mg/kg/day to either intact or spayed female dogs. The effects were assessed through clinical examination, haematology, serum biochemistry, ophthalmology and bone marrow aspirate examination. Ovariohysterectomy was performed and the uterus examined by histopathology. Vulva oedema and purulent vaginal discharge developed with 10 days of tamoxifen exposure in all groups. Pyometra was diagnosed after around 90 days of exposure in intact females with frequencies increasing during the following 30 days of exposure. Up to 50% of dogs within the groups developed retinitis but none of the dogs had signs of reduced visual acuity. The prevalence of retinitis in each group was similar after 120 days of exposure. Haematological, biochemical and bone marrow changes were not observed. Due to the high risk of developing pyometra after prolonged exposure to tamoxifen, only spayed animals should be given this medication. A dose of 0.8 mg tamoxifen/kg body weight/day is recommended when treating tamoxifen-responsive canine mammary tumors. Due to the high risk of developing pyometra, ovariohysterectomy is recommended.

  5. Evaluation of adverse effects in tamoxifen exposed healthy female dogs

    Directory of Open Access Journals (Sweden)

    Cavalcanti Guilherme AO

    2010-12-01

    Full Text Available Abstract Background Mammary tumors are among the most frequent neoplasms in female dogs, but the strategies employed in animal treatment are limited. In human medicine, hormone manipulation is used in cancer therapy. Tamoxifen citrate is a selective inhibitor of oestrogen receptors and exerts a potent anti-oestrogen effect on the mammary gland. The aim of this study was to evaluate the adverse effects when exposing healthy female dogs to tamoxifen. Methods Tamoxifen was administered for 120 days at a dose of 0.5 or 0.8 mg/kg/day to either intact or spayed female dogs. The effects were assessed through clinical examination, haematology, serum biochemistry, ophthalmology and bone marrow aspirate examination. Ovariohysterectomy was performed and the uterus examined by histopathology. Results Vulva oedema and purulent vaginal discharge developed with 10 days of tamoxifen exposure in all groups. Pyometra was diagnosed after around 90 days of exposure in intact females with frequencies increasing during the following 30 days of exposure. Up to 50% of dogs within the groups developed retinitis but none of the dogs had signs of reduced visual acuity. The prevalence of retinitis in each group was similar after 120 days of exposure. Haematological, biochemical and bone marrow changes were not observed. Due to the high risk of developing pyometra after prolonged exposure to tamoxifen, only spayed animals should be given this medication. Conclusions A dose of 0.8 mg tamoxifen/kg body weight/day is recommended when treating tamoxifen-responsive canine mammary tumors. Due to the high risk of developing pyometra, ovariohysterectomy is recommended.

  6. Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer.

    Science.gov (United States)

    Larsen, Sarah L; Yde, Christina W; Laenkholm, Anne-Vibeke; Rasmussen, Birgitte B; Duun-Henriksen, Anne Katrine; Bak, Martin; Lykkesfeldt, Anne E; Kirkegaard, Tove

    2015-04-08

    Resistance to antiestrogen therapy is a major clinical challenge in the treatment of estrogen receptor α (ER)-positive breast cancer. The aim of the study was to explore the growth promoting pathways of antiestrogen resistant breast cancer cells to identify biomarkers and novel treatment targets. Antiestrogen sensitive and resistant T47D breast cancer cell lines were used as model systems. Parental and fulvestrant resistant cell lines were subjected to a kinase inhibitor library. Kinase inhibitors preferentially targeting growth of fulvestrant resistant cells were identified and the growth inhibitory effect verified by dose-response cell growth experiments. Protein expression and phosphorylation were investigated by western blot analysis. Cell cycle phase distribution and cell death were analyzed by flow cytometry. To evaluate Aurora kinase B as a biomarker for endocrine resistance, immunohistochemistry was performed on archival primary tumor tissue from breast cancer patients who have received adjuvant endocrine treatment with tamoxifen. The selective Aurora kinase B inhibitor barasertib was identified to preferentially inhibit growth of fulvestrant resistant T47D breast cancer cell lines. Compared with parental cells, phosphorylation of Aurora kinase B was higher in the fulvestrant resistant T47D cells. Barasertib induced degradation of Aurora kinase B, caused mitotic errors, and induced apoptotic cell death as measured by accumulation of SubG1 cells and PARP cleavage in the fulvestrant resistant cells. Barasertib also exerted preferential growth inhibition of tamoxifen resistant T47D cell lines. Finally, high percentage of Aurora kinase B positive tumor cells was significantly associated with reduced disease-free and overall survival in 261 ER-positive breast cancer patients, who have received tamoxifen as first-line adjuvant endocrine treatment. Our results indicate that Aurora kinase B is a driving factor for growth of antiestrogen resistant T47D breast

  7. Effectiveness of adjuvant occupational therapy in employees with depression: design of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Hees Hiske L

    2010-09-01

    Full Text Available Abstract Background Major depressive disorder is among the medical conditions with the highest negative impact on work outcome. However, little is known regarding evidence-based interventions targeting the improvement of work outcomes in depressed employees. In this paper, the design of a randomized controlled trial is presented in order to evaluate the effectiveness of adjuvant occupational therapy in employees with depression. This occupational intervention is based on an earlier intervention, which was designed and proven effective by our research group, and is the only intervention to date that specifically targets work outcome in depressed employees. Methods/Design In a two-arm randomized controlled trial, a total of 117 participants are randomized to either 'care as usual' or ' care as usual' with the addition of occupational therapy. Patients included in the study are employees who are absent from work due to depression for at least 25% of their contract hours, and who have a possibility of returning to their own or a new job. The occupational intervention consists of six individual sessions, eight group sessions and a work-place visit over a 16-week period. By increasing exposure to the working environment, and by stimulating communication between employer and employee, the occupational intervention aims to enhance self-efficacy and the acquisition of more adaptive coping strategies. Assessments take place at baseline, and at 6, 12, and 18-month follow-ups. Primary outcome measure is work participation (hours of absenteeism and time until work resumption. Secondary outcome measures are work functioning, symptomatology, health-related quality of life, and neurocognitive functioning. In addition, cost-effectiveness is evaluated from a societal perspective. Finally, mechanisms of change (intermediate outcomes and potential patient-treatment matching variables are investigated. Discussion This study hopes to provide valuable knowledge

  8. Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial

    DEFF Research Database (Denmark)

    Munzone, E; Giobbie-Hurder, A; Gusterson, B A

    2015-01-01

    BACKGROUND: We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial. PATIENTS AND METHODS: The intention-to-treat BIG 1-98 monothera...

  9. The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma.

    Science.gov (United States)

    Trinh, Van Anh; Zobniw, Chrystia; Hwu, Wen-Jen

    2017-08-01

    Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy. Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

  10. Long-Term Outcomes of Adjuvant Mitotane Therapy in Patients With Radically Resected Adrenocortical Carcinoma.

    Science.gov (United States)

    Berruti, Alfredo; Grisanti, Salvatore; Pulzer, Alina; Claps, Mélanie; Daffara, Fulvia; Loli, Paola; Mannelli, Massimo; Boscaro, Marco; Arvat, Emanuela; Tiberio, Guido; Hahner, Stefanie; Zaggia, Barbara; Porpiglia, Francesco; Volante, Marco; Fassnacht, Martin; Terzolo, Massimo

    2017-04-01

    In 2007, a retrospective case-control study provided evidence that adjuvant mitotane prolongs recurrence-free survival (RFS) in patients with radically resected adrenocortical carcinoma (ACC). We aimed to confirm the prognostic role of adjuvant mitotane in the same series after 9 additional years of follow-up. One hundred sixty-two ACC patients who did not recur or die after a landmark period of 3 months were considered. Forty-seven patients were enrolled in four Italian centers where adjuvant mitotane was routinely recommended (mitotane group), 45 patients in four Italian centers where no adjuvant strategy was undertaken (control group 1), and 70 German patients left untreated after surgery (control group 2). The primary aim was RFS, the secondary was overall survival. An increased risk of recurrence was found in both control cohorts [group 1: hazard ratio (HR) = 2.98; 95% confidence interval (CI), 1.75 to 5.09; P < 0.0001; group 2: HR = 2.61; 95% CI, 1.56 to 4.36; P < 0.0001] compared with the mitotane group. The risk of death was higher in control group 1 (HR = 2.03; 95% CI, 1.17 to 3.51; P = 0.011) but not in control group 2 (HR = 1.60; 95% CI, 0.94 to 2.74; P = 0.083), which had better prognostic factors and more aggressive treatment of recurrences than control group 1. The benefit of adjuvant mitotane on RFS was observed regardless of the hormone secretory status. Adjuvant mitotane is associated with prolonged RFS, without any apparent influence by the tumor secretory status. The retrospective nature of the study is a major limitation. Copyright © 2017 by the Endocrine Society

  11. Valor da ultra-sonografia na avaliação das alterações endometriais em pacientes tratadas com tamoxifeno Value of sonographic endometrial findings in patients under tamoxifen therapy

    Directory of Open Access Journals (Sweden)

    Arildo Corrêa Teixeira

    2007-12-01

    Full Text Available OBJETIVO: Avaliar as alterações endometriais por meio da ultra-sonografia transvaginal e correlacioná-las com os achados da histeroscopia e histologia, em pacientes submetidas a tratamento com tamoxifeno. MATERIAIS E MÉTODOS: No período de janeiro de 2003 a dezembro de 2005, foram incluídas pacientes com câncer de mama usuárias de tamoxifeno que apresentaram espessamento endometrial acima de 5 mm. Os achados foram correlacionados com os dados de histeroscopia e anatomopatologia. RESULTADOS: Foram selecionadas 25 pacientes com idade média de 62,6 anos. O tempo médio do diagnóstico do câncer foi de 4,3 anos e do uso de tamoxifeno, três anos. Vinte pacientes eram assintomáticas (80% e as demais apresentaram sangramento (20%. À ultra-sonografia, 16% apresentaram espessamento endometrial entre 5 mm e 8 mm, 40% entre 9 mm e 15 mm, e 44% acima de 15 mm. Ao estudo com a histeroscopia, 40% apresentaram atrofia, 16% atrofia cística, 28% pólipos, e 16% lesão hiperplásica. O estudo anatomopatológico apresentou-se normal em 35,2% dos casos e mostrou atrofia em 5,8%, pólipo em 29,4% e hiperplasia em 11,7%. Foi observado um caso de adenocarcinoma (5,8%. CONCLUSÃO: A ultra-sonografia associada à histeroscopia apresentam-se como importantes aliados na avaliação de pacientes usuárias de tamoxifeno. A detecção de espessamento endometrial à ultra-sonografia apresenta baixa especificidade, enquanto a histeroscopia é mais acurada na detecção de pólipos, hiperplasia e alterações neoplásicas.OBJECTIVE: To evaluate endometrial alterations by means of transvaginal ultrasound and to correlate them with hysteroscopic and histological findings in patients under tamoxifen therapy. MATERIALS AND METHODS: The present study was developed in the period between January 2003 and December 2005, including patients under tamoxifen therapy for breast cancer, and presenting with endometrial thickening > 5 mm. The sonographic findings were correlated

  12. Effect of probucol combined with atorvastatin adjuvant therapy on serum indexes of acute cerebral infarction patients during rehabilitation period

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    Li Zhang

    2016-06-01

    Full Text Available Objective: To analyze the effect of probucol combined with atorvastatin adjuvant therapy on serum indexes of acute cerebral infarction patients in rehabilitation period. Methods: A total of 102 patients with acute cerebral infarction were treated in our hospital from August 2011 to June 2015, were confirmed by magnetic resonance imaging and were randomly divided into observation group 51 cases and control group 51 cases according to the order of hospitalization. Control group received atorvastatin treatment alone, observation group received probucol combined with atorvastatin adjuvant therapy, and then differences in levels of serum CXCL16, HMGB1, CD40L and Fibulin-5, P-selectin, NPY, CGRP, visfatin and others, chemokines and inflammation-related factors, vascular endothelial cells and fibrinolytic function, etc were compared between two groups after treatment. Results: Serum CXCL16, HMGB1, CD40L and Fibulin-5 levels of observation group after treatment were lower than those of control group; serum P-selectin, NPY, visfatin, UCH-L1, sVCAM-1 and SAA levels of observation group after treatment were lower than those of control group while CGRP level was higher than that of control group; serum CCL-19, CCL-21, YKL-40, IL-33 and IL- 18 values of observation group after treatment were lower than those of control group; serum vWF, PAI-1 and plasminogen levels of observation group after treatment were lower than those of control group while 6-K-PGF1α and tPA levels were higher than those of control group. Conclusions: Probucol combined with atorvastatin adjuvant therapy for acute cerebral infarction patients in rehabilitation period can effectively optimize patients’ general status and avoid re-infarction in recovery period, and it has positive clinical significance.

  13. Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels

    DEFF Research Database (Denmark)

    Vihinen, Pia; Tervahartiala, Taina; Sorsa, Timo

    2015-01-01

    Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre......-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP......-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median...

  14. Merkel cell carcinoma: value of sentinel lymph-node status and adjuvant radiation therapy.

    Science.gov (United States)

    Servy, A; Maubec, E; Sugier, P E; Grange, F; Mansard, S; Lesimple, T; Marinho, E; Couturaud, B; Girod, A; Albert, S; Dendale, R; Calitchi, E; Sarda, L; Chanal, J; Deschamps, L; Sastre-Garau, X; Laroche, L; Crickx, B; Avril, M F

    2016-05-01

    Sentinel lymph-node (LN) biopsy (SLNB) is a valuable tool to assess the regional LN status in Merkel cell carcinoma (MCC). However, its prognostic value is still debated. This study was undertaken to assess SLNB usefulness for MCC management and to determine the impact of SLNB status on disease-free survival (DFS) and overall survival (OS) by comparing SLNB-positive versus -negative patients according to demographic, clinical and treatment characteristics. In this retrospective, multicenter observational study, SLNB was proposed to all patients referred for clinically N0 MCC. Treatment schedule consisted of wide-margin surgical resection of primary MCC followed by adjuvant radiation therapy (aRT) to the primary site and, for SLNB-positive patients, radical LN dissection followed by regional aRT. Univariate and multivariate analyses determined factors associated with DFS and OS. Among 87 patients with successful SLNB, 21 (24.1%) were SLNB-positive. Median follow-up for the entire series was 39 months; respective 3-year DFS and OS rates were 73% and 81.4%, respectively. Univariate analysis (all patients) identified SLNB-negativity as being associated with prolonged OS (P = 0.013) and aRT (all sites considered) was associated with longer DFS (P = 0.004) and OS (P = 0.018). Multivariate analysis (all patients) retained SLNB status and aRT (all sites considered) as being associated with improved DFS (P = 0.014 and 0.0008) and OS (P = 0.0020 and 0.0019). Moreover, for SLNB-negative patients, tumor-bed irradiation was also significantly associated with prolonged DFS (P = 0.006) and OS (P = 0.014). The present study demonstrates that SLNB-negativity is a strong predictor of longer DFS and OS in stage I and II MCC patients. The similar benefit for aRT on tumor bed observed in this study has to be confirmed by a prospective study. The results advocate for SLNB being considered to all MCC patients. © The Author 2016. Published by Oxford University Press on behalf of the

  15. Differentiated thyroid cancer lymph-node relapse. Role of adjuvant radioactive iodine therapy after lymphadenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Piccardo, Arnoldo; Bottoni, Gianluca; Dib, Bassam; Altrinetti, Vania; Massollo, Michela; Bossert, Irene; Cabria, Manlio [E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Puntoni, Matteo [Galliera Hospital, Clinical Trial Unit, Office of the Scientific Director, Genoa (Italy); Treglia, Giorgio; Giovanella, Luca [Oncology Institute of Southern Switzerland, Department of Nuclear Medicine and PET/CT Centre, Bellinzona (Switzerland); Foppiani, Luca [Galliera Hospital, Internal Medicine, Genoa (Italy); Bertoli, Mattia; Bertagna, Francesco [University of Brescia and Spedali Civili di Brescia, Department of Nuclear Medicine, Brescia (Italy); Catrambone, Ugo; Arlandini, Anselmo [Galliera Hospital, Department of Surgery, Thyroid Centre, Genoa (Italy)

    2017-06-15

    Our purpose as to evaluate the impact of adjuvant radioactive iodine therapy (RAI) on prognosis, as assessed by progression-free survival (PFS) and overall survival (OS), in patients affected by differentiated thyroid carcinoma (DTC) lymph-node relapse and previously treated with lymphadenectomy. We retrospectively evaluated DTC patients treated with lymph-node dissection for disease relapse. All patients had previously undergone total thyroidectomy and radioiodine remnant ablation (RRA). We used clinical and histological data obtained during follow-up to assess response and outcome. By means of univariate and multivariate time-to-event analyses, we assessed the impact of RAI on outcome (PFS and OS) and the prognostic role of thyroglobulin (Tg) levels under suppression with levothyroxine (Tg-on) measured 1-3 months after lymphadenectomy and of other risk factors. We evaluated 113 patients (age at diagnosis: median 41 years, interquartile range: 31-59), 64 of whom were treated with RAI. Over a median follow-up time of 5.7 years, 27 patients showed disease progression and 13 died. Kaplan-Meier PFS and OS curves showed that age on diagnosis, tumor histology, tumor size, DTC aggressive variant, and Tg-on were associated with prognosis. Patients with Tg-on ≥1 ng/ml treated with RAI showed a better PFS (Log-rank pp 0.001) and OS (p = 0.005) than untreated patients, while no effect of RAI was observed in patients with Tg-on <1 ng/ml. Multivariate models showed that age, Tg-on (≥1 vs. < 1 ng/ml, HR: 18.2, 95% CI: 5.09-64.8, p = 0.001) and RAI (Yes vs. No, HR: 0.36,95%CI: 0.15-0. 9, p = 0.02) remained the only independent factors associated with PFS, but only age and Tg-on remained significantly associated with OS (HR: 8.31, 95%CI:1.56-44.3, p = 0.01). Nonetheless, patients treated with RAI showed a lower risk of mortality (HR: 0.34, 95%CI: 0.1-1.15 p = 0.08) than untreated patients. RAI after lymphadenectomy for DTC relapse is significantly associated with better PFS

  16. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ost, Piet, E-mail: piet.ost@ugent.be [Department of Radiotherapy, Ghent University Hospital (Belgium); Cozzarini, Cesare [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital (Belgium); Fiorino, Claudio [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Potter, Bruno [Department of Radiotherapy, Ghent University Hospital (Belgium); Briganti, Alberto [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Nagler, Evi V.T. [Department of Nephrology, Ghent University Hospital (Belgium); Montorsi, Francesco [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Fonteyne, Valerie [Department of Radiotherapy, Ghent University Hospital (Belgium); Di Muzio, Nadia [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy)

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  17. The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

    Science.gov (United States)

    Dorchies, Olivier M; Reutenauer-Patte, Julie; Dahmane, Elyes; Ismail, Heham M; Petermann, Olivier; Patthey- Vuadens, Ophélie; Comyn, Sophie A; Gayi, Elinam; Piacenza, Tony; Handa, Robert J; Décosterd, Laurent A; Ruegg, Urs T

    2013-02-01

    Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.

  18. Quantitative detection of HER2 protein concentration in breast cancer tissue does not increase the number of patients eligible for adjuvant HER2-targeted therapy

    DEFF Research Database (Denmark)

    Bechmann, Troels; Olsen, Dorte Aalund; Jakobsen, Erik Hugger

    2013-01-01

    Human epidermal growth factor receptor-2 (HER2) is overexpressed in 15-20% of breast cancer patients and is associated with an aggressive tumor and a poor prognosis. Currently, patients are selected for adjuvant HER2-targeted therapy based on HER2 status by immunohistochemistry (IHC) and fluoresc......Human epidermal growth factor receptor-2 (HER2) is overexpressed in 15-20% of breast cancer patients and is associated with an aggressive tumor and a poor prognosis. Currently, patients are selected for adjuvant HER2-targeted therapy based on HER2 status by immunohistochemistry (IHC...... by Centaur, but not treated with adjuvant HER2-targeted therapy, compared to patients defined as HER2-positive by IHC/FISH and therefore treated with adjuvant HER2-targeted therapy. Tumor tissue was obtained at primary surgery from 415 breast cancer patients between 2004 and 2010. HER2 status was determined...... by quantitative immunoassay of fresh-frozen tissue and by IHC/FISH of corresponding paraffin-embedded tissue. We compared the clinical outcome in four groups of patients defined by tissue HER2 status and adjuvant HER2-targeted therapy. The final analysis included 379 patients after a median follow-up of 3.9 years...

  19. Chemotherapy for endometrial carcinoma (GOGO-EM1 study): TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy.

    Science.gov (United States)

    Egawa-Takata, Tomomi; Ueda, Yutaka; Kuragaki, Chie; Miyake, Takahito; Miyatake, Takashi; Fujita, Masami; Yoshino, Kiyoshi; Nakashima, Ryuichi; Okazawa, Mika; Tsutsui, Tateki; Morishige, Ken-Ichirou; Kimura, Tadashi; Yamasaki, Masato; Nishizaki, Takamichi; Nagamatsu, Masaaki; Ito, Kimihiko; Asada, Masahiro; Ogita, Kazuhide; Wakimoto, Akinori; Yamamoto, Toshiya; Nishio, Yukihiro; Enomoto, Takayuki

    2011-12-01

    TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determined. Phase I/II prospective study for TEC therapy was performed. A retrospective comparison of the prognosis between adjuvant TEC therapy and radiation for completely resected cases with risk factors was also performed. The recommended dose of TEC therapy was determined to be paclitaxel 150 mg/m(2), epirubicin 50 mg/m(2), and carboplatin AUC 4. A TEC regimen at this dose level was shown to be tolerable. The response rate and median overall survival were 74% and 37 months for those with advanced primary disease (Group B) and 50% and 26 months for recurrent tumors (Group C), respectively. A retrospective comparison showed that adjuvant TEC therapy for completely resected stage III cases improved their prognosis when compared to an adjuvant radiation therapy. TEC therapy was demonstrated to be a tolerable and effective treatment, not only as a remission-induction therapy for advanced and recurrent endometrial carcinomas but also as the adjuvant therapy.

  20. Effect of screening and adjuvant therapy on mortality from breast cancer

    NARCIS (Netherlands)

    D.A. Berry (Donald); K.A. Cronin (Kathleen); S.K. Plevritis (Sylvia); D.G. Fryback (Dennis); L. Clarke (Lauren); M. Zelen (Marvin); J.S. Mandelblatt (Jeanne); A.Y. Yakovlev (Andrei); J.D.F. Habbema (Dik); E. Feuer (Eric)

    2005-01-01

    textabstractBACKGROUND: We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000. METHODS: A consortium of investigators developed seven independent

  1. Müllerian adenosarcoma of the uterus with sarcomatous overgrowth following tamoxifen treatment for breast cancer

    Directory of Open Access Journals (Sweden)

    Carvalho Filomena Marino

    2000-01-01

    Full Text Available Müllerian adenosarcoma with sarcomatous overgrowth presented by a 52-year-old female patient after adjuvant tamoxifen treatment for breast carcinoma is described. The diagnosis was made on histological basis after curettage and complementary total hysterectomy with bilateral salpingo-oophorectomy. The immunohistochemical study showed high expression of estrogen receptors in the epithelial component of the lesion and irregularly positive findings in the stroma. The proliferative activity evaluated by Ki-67 immunoexpression was higher in the stroma than the epithelium. Some of the stromal cells showed rhabdomyoblastic differentiation. The association of tamoxifen use and development of mesenchymal neoplasms is discussed.

  2. Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy.

    Science.gov (United States)

    Santa-Maria, Cesar A; Blackford, Amanda; Nguyen, Anne T; Skaar, Todd C; Philips, Santosh; Oesterreich, Steffi; Rae, James M; Desta, Zeruesenay; Robarge, Jason; Henry, Norah Lynn; Storniolo, Anna M; Hayes, Daniel F; Blumenthal, Roger S; Ouyang, Pamela; Post, Wendy S; Flockhart, David A; Stearns, Vered

    2016-03-15

    Aromatase inhibitors can exert unfavorable effects on lipid profiles; however, previous studies have reported inconsistent results. We describe the association of single-nucleotide polymorphisms (SNP) in candidate genes with lipid profiles in women treated with adjuvant aromatase inhibitors. We conducted a prospective observational study to test the associations between SNPs in candidate genes in estrogen signaling and aromatase inhibitor metabolism pathways with fasting lipid profiles during the first 3 months of aromatase inhibitor therapy in postmenopausal women with early breast cancer randomized to adjuvant letrozole or exemestane. We performed genetic association analysis and multivariable linear regressions using dominant, recessive, and additive models. A total of 303 women had complete genetic and lipid data and were evaluable for analysis. In letrozole-treated patients, SNPs in CYP19A1, including rs4646, rs10046, rs700518, rs749292, rs2289106, rs3759811, and rs4775936 were significantly associated with decreases in triglycerides by 20.2 mg/dL and 39.3 mg/dL (P < 0.00053), respectively, and with variable changes in high-density lipoprotein (HDL-C) from decreases by 4.2 mg/dL to increases by 9.8 mg/dL (P < 0.00053). Variants in CYP19A1 are associated with decreases in triglycerides and variable changes in HDL-C in postmenopausal women on adjuvant aromatase inhibitors. Future studies are needed to validate these findings, and to identify breast cancer survivors who are at higher risk for cardiovascular disease with aromatase inhibitor therapy. ©2015 American Association for Cancer Research.

  3. A high level of estrogen-stimulated proteins selects breast cancer patients treated with adjuvant endocrine therapy with good prognosis

    DEFF Research Database (Denmark)

    L H Weischenfeldt, Katrine; Kirkegaard, Tove; Rasmussen, Birgitte B

    2017-01-01

    BACKGROUND: Adjuvant endocrine therapy has significantly improved survival of estrogen receptor α (ER)-positive breast cancer patients, but around 20% relapse within 10 years. High expression of ER-stimulated proteins like progesterone receptor (PR), Bcl-2 and insulin-like growth factor receptor I...... (IGF-IR) is a marker for estrogen-driven cell growth. Therefore, patients with high tumor levels of these proteins may have particularly good prognosis following adjuvant endocrine therapy. PATIENTS AND METHODS: Archival tumor tissue was available from 1323 of 1396 Danish breast cancer patients......, univariate and multivariate analysis revealed HR (95% CI) and p values for disease-free survival (DFS) of 2.00 (1.20-3.22), 0.008 and 1.70 (1.01-2.84), 0.04 and for the overall survival (OS) of 2.33 (1.19-4.57), 0.01 and 1.90 (0.97-3.79), 0.06, respectively. The high ER activity profile did not disclose...

  4. Impact of radiation treatment parameters and adjuvant systemic therapy on cosmetic outcomes after accelerated partial breast irradiation using 3-dimensional conformal radiation therapy technique.

    Science.gov (United States)

    Mellon, Eric A; Sreeraman, Radhika; Gebhardt, Brian J; Mierzejewski, Aline; Correa, Candace R

    2014-01-01

    There are concerns regarding cosmetic outcomes of 3-dimensional conformal accelerated partial breast radiation therapy (3DCRT APBI). Associations between cosmetic outcomes and treatment parameters or receipt of adjuvant systemic therapy were sought to guide 3DCRT APBI. An analysis of cosmetic outcomes among patients treated with 3DCRT APBI at Moffitt Cancer Center was performed. Overall cosmesis was evaluated using modified Harvard criteria and toxicity outcomes were graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients were treated to 38.5 Gy in 3.85 Gy twice daily fractions per dose-volume objectives specified in the National Surgical Adjuvant Breast and Bowel B-39/Radiation Therapy Oncology Group 0413 (NSABP B-39/RTOG 0413) trial. At least 1 evaluation was available for 97 treated breasts (94 women) with median follow-up of 17.2 months (range, 1-60 months). Most breasts (90.7%) had grade 1 to 2 (excellent to good) overall cosmesis. Nine breasts (9.3%) had grade 3 to 4 (fair to poor) overall cosmesis, secondary to >25% asymmetry in 5 patients, grade 3 fibrosis in 3 patients, and fat necrosis in 1 patient. Increasing percentage of ipsilateral breast volume receiving more than 50% of the prescription dose (V50%) correlated with less than excellent cosmesis (P radiation therapy dose-volume constraints, particularly ipsilateral breast V50%. © 2014. Published by Elsevier Inc. All rights reserved.

  5. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Mouridsen, Henning T; Jensen, Maj-Britt

    2010-01-01

    BACKGROUND: The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single-agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) against no adjuvant systemic therapy in high-risk breast...... cancer patients. The authors report the results from that trial after a potential follow-up of 25 years. METHODS: Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly...... for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) intravenously on Days 1 and 8 every 4 weeks for 12 cycles...

  6. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

    Science.gov (United States)

    Lesiuk, Teresa

    2016-01-01

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients’ narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

  7. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer.

    Science.gov (United States)

    Lesiuk, Teresa

    2016-08-09

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients' narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided.

  8. Diphenhydramine as adjuvant therapy for acute migraine. An ED-based randomized clinical trial

    Science.gov (United States)

    Friedman, Benjamin W; Cabral, Lisa; Adewunmi, Victoria; Solorzano, Clemencia; Esses, David; Bijur, Polly E; Gallagher, E John

    2015-01-01

    . Of patients randomized to diphenhydramine, 40% (40/100) reported sustained relief at 48 hours, as did 37% (38/103) of patients randomized to placebo (95%CI for difference of 3%: −10, 16%). One hour after medication administration, those randomized to diphenhydramine improved by a mean of 5.1 on the 0 to 10 scale versus 4.8 for those randomized to placebo (95%CI for difference of 0.3: −0.6, 1.1). 85% (84/99) of the patients in the diphenhydramine arm reported they would want the same medication combination during a subsequent ED visit, as did 76% (77/102) of those who received placebo (95%CI for difference of 9%: −2, 20%). Median ED length of stay was 122 minutes (IQR: 84, 180) in the diphenhydramine group and 139 minutes (IQR: 90, 235) in the placebo arm. Rates of side effects, including akathisia, were comparable between the groups. Conclusions Intravenous diphenhydramine, when administered as adjuvant therapy with metoclopramide, does not improve migraine outcomes. PMID:26320523

  9. Does Adipose-derived Stromal Cell Adjuvant Therapy for Fragmented Medial Coronoid Process in Dogs Influence Outcome? A Pilot Project

    Directory of Open Access Journals (Sweden)

    Kristina M Kiefer

    2016-11-01

    Full Text Available Objective: The primary objective of this study was to identify adverse events associated with multiple intra-articular injections of adipose stromal cell (ASC therapy and secondarily to objectively assess the therapeutic effect of ASC therapy for treatment of fragmented medial coronoid process (FMCP in dogs when used as an adjuvant to standard of care (SOC treatment. Background: Preliminary trials assessing autologous ASC therapy to treat osteoarthritis indicate a positive impact on clinical signs, but assessment of donated, allogeneic ASC therapy is lacking.Evidentiary value: This prospective, randomised, controlled trial in dogs (n=30 provides objective evidence for clinical practitioners regarding ASC therapy in a naturally occurring osteoarthritic disease model.Methods: Dogs diagnosed with FMCP and osteoarthritis were enrolled. All dogs had arthroscopic fragment removal and proximal ulnar osteotomy (PUO and were assigned into three groups (n=10/group: 1 control group with no further treatment beyond the PUO and fragment removal (SOC, 2 PUO + autologous ASCs and 3 PUO+ allogeneic ASCs. Each dog had force platform gait analysis, Canine Brief Pain Inventory (CBPI questionnaires, and delayed gadolinium enhanced magnetic resonance imaging scores prior to and six months after therapeutic intervention.Results: No serious adverse events were reported in any participant. 3/10 dogs in the control group, 3/10 autologous ASC group and 7/10 allogeneic ASC group participants were assessed as successful outcomes.Conclusion: This study provides preliminary safety data for the use of intra-articular allogeneic ASC therapy to treat osteoarthritis, and justification for larger clinical studies.Application: Clinical practitioners considering ASC therapy within their practice are provided with additional evidence of autologous ASC therapy for osteoarthritis. Researchers committed to developing and generating effective ASC therapies are provided with safety

  10. Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Ju; Rhee, Woo Joong; Choi, Seo Hee; Kim, Gwi Eon; Kim, Yong Bae [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, EunJi; Kim, Sang Wun; Kim, Sung Hoon [Dept. of Radiation Oncology, Obstetrics and Gynecology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic

  11. Drug switch because of treatment-related adverse side effects in endocrine adjuvant breast cancer therapy: how often and how often does it work?

    Science.gov (United States)

    Güth, Uwe; Myrick, Mary Elizabeth; Schötzau, Andreas; Kilic, Nerbil; Schmid, Seraina Margaretha

    2011-10-01

    Therapy-related adverse side effects are a main reason for non-persistence to adjuvant endocrine breast cancer therapy. This study reports frequency of drug-related adverse side effects that were so severe that a modification of the therapy was necessary. We evaluated how many patients discontinued adjuvant endocrine therapy because of these side effects (non-persistence). Last, we analyzed how often a drug switch was undertaken for this reason and how often this measure led to the patient successfully continuing their endocrine therapy. Data concerning all postmenopausal breast cancer patients (≤ 80 years), who initiated endocrine adjuvant therapy between 1998 and 2008 in a Swiss breast center (n = 400), were analyzed. Out of these 400 women, 37 (9.3%) were defined as being non-persistent to the therapy; out of these, 24 (64.9%) because of therapy-related side effects. About 78 patients (19.5%) suffered from severe therapy-related side effects that made a modification of therapy necessary. Out of these 78 cases, 14 patients (17.9%) stopped the therapy without attempting a drug switch (non-persistence). In 64 patients (82.1%; 16% of all women who started endocrine therapy), a drug switch was undertaken. Out of these 64 cases, in 52 cases (81.3%) endocrine therapy was completed after therapy modification. Patients who reported one major adverse effect were more likely to continue the endocrine therapy after a drug switch (P = 0.048) compared with those who suffered from at least two different side effects. In 10 of the 64 cases (15.6%), modification of the therapy was not successful and the patients stopped the treatment prematurely (non-persistence) because of ongoing side effects. In cases when therapy-related side effects occur, a drug switch is a promising step to further improve persistence and, by doing so, the outcome of breast cancer patients.

  12. Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program

    DEFF Research Database (Denmark)

    See, William A; Wirth, Manfred P; McLeod, David G

    2002-01-01

    We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer.......We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer....

  13. The formation of estrogen-like tamoxifen metabolites and their influence on enzyme activity and gene expression of ADME genes.

    Science.gov (United States)

    Johänning, Janina; Kröner, Patrick; Thomas, Maria; Zanger, Ulrich M; Nörenberg, Astrid; Eichelbaum, Michel; Schwab, Matthias; Brauch, Hiltrud; Schroth, Werner; Mürdter, Thomas E

    2018-03-01

    Tamoxifen, a standard therapy for breast cancer, is metabolized to compounds with anti-estrogenic as well as estrogen-like action at the estrogen receptor. Little is known about the formation of estrogen-like metabolites and their biological impact. Thus, we characterized the estrogen-like metabolites tamoxifen bisphenol and metabolite E for their metabolic pathway and their influence on cytochrome P450 activity and ADME gene expression. The formation of tamoxifen bisphenol and metabolite E was studied in human liver microsomes and Supersomes™. Cellular metabolism and impact on CYP enzymes was analyzed in upcyte® hepatocytes. The influence of 5 µM of tamoxifen, anti-estrogenic and estrogen-like metabolites on CYP activity was measured by HPLC MS/MS and on ADME gene expression using RT-PCR analyses. Metabolite E was formed from tamoxifen by CYP2C19, 3A and 1A2 and from desmethyltamoxifen by CYP2D6, 1A2 and 3A. Tamoxifen bisphenol was mainly formed from (E)- and (Z)-metabolite E by CYP2B6 and CYP2C19, respectively. Regarding phase II metabolism, UGT2B7, 1A8 and 1A3 showed highest activity in glucuronidation of tamoxifen bisphenol and metabolite E. Anti-estrogenic metabolites (Z)-4-hydroxytamoxifen, (Z)-endoxifen and (Z)-norendoxifen inhibited the activity of CYP2C enzymes while tamoxifen bisphenol consistently induced CYPs similar to rifampicin and phenobarbital. On the transcript level, highest induction up to 5.6-fold was observed for CYP3A4 by tamoxifen, (Z)-4-hydroxytamoxifen, tamoxifen bisphenol and (E)-metabolite E. Estrogen-like tamoxifen metabolites are formed in CYP-dependent reactions and are further metabolized by glucuronidation. The induction of CYP activity by tamoxifen bisphenol and the inhibition of CYP2C enzymes by anti-estrogenic metabolites may lead to drug-drug-interactions.

  14. A cohort study of ethnic differences in use of adjuvant chemotherapy and radiation therapy for breast cancer in New Zealand.

    Science.gov (United States)

    Seneviratne, Sanjeewa; Campbell, Ian; Scott, Nina; Lawrenson, Ross

    2017-01-21

    Ethnic and socioeconomic inequities in use of breast cancer adjuvant therapy are well documented in many countries including the USA, and are known to contribute to lower breast cancer survival among minority ethnic and socioeconomically deprived women. We investigated ethnic and socioeconomic inequities in use of adjuvant radiotherapy and chemotherapy in a cohort of women with invasive breast cancer in New Zealand. All women with newly diagnosed invasive breast cancer during 1999-2012 were identified from the Waikato Breast Cancer Register. Rates of chemotherapy use and radiotherapy use were assessed in women who were deemed to be eligible for chemotherapy (n = 1212) and radiotherapy (n = 1708) based on guidelines. Factors associated with use of chemotherapy and radiation therapy were analysed in univariate and multivariate regression models, adjusting for covariates. Overall, rates of chemotherapy and radiotherapy use were 69% (n = 836) and 87.3% (n = 1491), respectively. In the multivariate model, significantly lower rates of radiotherapy use were associated with Māori compared with NZ European (Odds Ratio [OR] = 0.63, 0.40-0.98), presence of comorbidity (OR = 0.49, 0.34-0.72), distance from hospital of over 100km (OR = 0.47, 0.23-0.96), mastectomy compared with breast conserving surgery (OR = 0.32, 0.17-0.56) and non-screen compared with screen detection (OR = 0.53, 0.35-0.79). No significant associations were observed between chemotherapy use and ethnic or socio-demographic factors. Improving access for radiotherapy, especially for women who are at a higher risk of not receiving optimum cancer therapy due to ethnicity, geography or socioeconomic status need to be recognized as a priority to reduce inequities in breast cancer care in New Zealand.

  15. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

    Science.gov (United States)

    Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

    2015-06-01

    For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice. © 2015 by American Society of Clinical Oncology.

  16. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

    Science.gov (United States)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    International Nuclear Information System (INIS)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-01-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits

  18. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, In Ja [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Kim, Hee Cheol [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Nam Kyu [Section of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong-Rok [Department of Surgery, Chonnam National University Hwansun Hospital, Gwangju (Korea, Republic of); Kang, Sung-Bum [Department of Surgery, Seoul National University Bungdang Hospital, Bundang (Korea, Republic of); Choi, Gyu-Seog [Division of Colorectal Cancer Center, Kyungpook National University Medical Center, Daegu (Korea, Republic of); Lee, Kang Young [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seon-Hahn [Department of Surgery, Korea University Anam Hospital, Seoul (Korea, Republic of); Oh, Seung Taek [Department of Surgery, Seoul St. Mary Hospital, Catholic University, Seoul (Korea, Republic of); Lim, Seok-Byung; Kim, Jin Cheon [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Oh, Jae Hwan; Kim, Sun Young [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Lee, Woo Yong [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jung Bok [Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Yu, Chang Sik, E-mail: csyu@amc.seoul.kr [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of)

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  19. 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...

  20. Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Martina E., E-mail: m.schmidt@dkfz.de [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Meynköhn, Anna; Habermann, Nina [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Wiskemann, Joachim [Division of Medical Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Oelmann, Jan; Hof, Holger; Wessels, Sabine [Department of Radiation Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Klassen, Oliver [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Debus, Jürgen; Potthoff, Karin [Department of Radiation Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Steindorf, Karen; Ulrich, Cornelia M. [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany)

    2016-02-01

    Purpose: To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. Methods and Materials: Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naïve participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research and Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R{sup 2} effect-size measures for mediation were calculated. Results: The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL-1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. Conclusions: This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy in breast

  1. Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial

    International Nuclear Information System (INIS)

    Schmidt, Martina E.; Meynköhn, Anna; Habermann, Nina; Wiskemann, Joachim; Oelmann, Jan; Hof, Holger; Wessels, Sabine; Klassen, Oliver; Debus, Jürgen; Potthoff, Karin; Steindorf, Karen; Ulrich, Cornelia M.

    2016-01-01

    Purpose: To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. Methods and Materials: Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naïve participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research and Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R 2 effect-size measures for mediation were calculated. Results: The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL-1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. Conclusions: This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy in breast

  2. Efficacy and Safety Assessment of the Addition of Bevacizumab to Adjuvant Therapy Agents in Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Fariba Ahmadizar

    Full Text Available To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients.PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials comparing bevacizumab and adjuvant therapy with adjuvant therapy alone published from January 1966 to 7th of May 2014. Progression free survival, overall survival, overall response rate, safety and quality of life were analyzed using random- or fixed-effects models according to the PRISMA guidelines. We obtained data from 44 randomized controlled trials (30,828 patients. Combining bevacizumab with different adjuvant therapies resulted in significant improvement of progression free survival (log hazard ratio, 0.87; 95% confidence interval (CI, 0.84-0.89, overall survival (log hazard ratio, 0.96; 95% CI, 0.94-0.98 and overall response rate (relative risk, 1.46; 95% CI: 1.33-1.59 compared to adjuvant therapy alone in all studied tumor types. In subgroup analyses, there were no interactions of bevacizumab with baseline characteristics on progression free survival and overall survival, while overall response rate was influenced by tumor type and bevacizumab dose (p-value: 0.02. Although bevacizumab use resulted in additional expected adverse drug reactions except anemia and fatigue, it was not associated with a significant decline in quality of life. There was a trend towards a higher risk of several side effects in patients treated by high-dose bevacizumab compared to the low-dose e.g. all grade proteinuria (9.24; 95% CI: 6.60-12.94 vs. 2.64; 95% CI: 1.29-5.40.Combining bevacizumab with different adjuvant therapies provides a survival benefit across all major subsets of patients, including by tumor type, type of adjuvant therapy, and duration and dose of bevacizumab therapy. Though bevacizumab was associated with increased risks of some adverse drug reactions such as hypertension and bleeding

  3. Combinational treatment of gap junctional activator and tamoxifen in breast cancer cells.

    Science.gov (United States)

    Gakhar, Gunjan; Hua, Duy H; Nguyen, Thu Annelise

    2010-01-01

    Tamoxifen is a drug of choice for endocrine-responsive breast tumor patients. However, tamoxifen resistance has become a major concern for the treatment of breast cancer. Combinational therapies of tamoxifen and different drugs are being frequently studied. In this study, we tested the efficacy of substituted quinolines (code name=PQ1; a gap junctional activator) in combination with tamoxifen in T47D cells. Colony growth assay was performed using soft agar to measure the colony growth, whereas cell proliferation was measured by the MTT assay in T47D cells. The level of Ki67, survivin, and BAX was measured using confocal microscopy along with western blot analysis. Apoptosis-bromodeoxyuridine triphosphate labeling was also examined in the induced treatment of T47D cells. We observed a 55% decrease in the colony growth in the presence of combination of PQ1 and tamoxifen, whereas tamoxifen alone had little effect. A combination of 10 micromol/l tamoxifen and 200 or 500 nmol/l PQ1 resulted in only 16% cell viability compared with controls at 48 h in T47D cells by the MTT assay. We found a significant increase in BAX protein at 1 h in the presence of 500 nmol/l PQ1 alone, 10 micromol/l tamoxifen alone, and the combination of PQ1 and tamoxifen. A two-fold increase was observed in active caspase 3 in the presence of combinational treatment of 10 micromol/l tamoxifen and 200 or 500 nmol/l PQ1. In addition, flow cytometric analysis showed a 50% increase in the number of apoptotic cells in the presence of the combination of tamoxifen and PQ1 compared with the control. Furthermore, the results show that combinational treatment of tamoxifen and PQ1 significantly reduces the expression of survivin in T47D cells. Gap junction inhibitor studies with carbenexolone were also performed confirming the role of gap junctions in cell proliferation and cell death. The combinational treatment of PQ1 and tamoxifen has a significant increase in BAX expression, caspase 3 activation, and DNA

  4. Postoperative adjuvant combination therapy with doxorubicin and noncytotoxic suramin in dogs with appendicular osteosarcoma.

    Science.gov (United States)

    Alvarez, Francisco J; Kisseberth, William; Hosoya, Kenji; Lara-Garcia, Ana; Kosarek, Carrie; Murahari, Sridhar; Au, Jessie L-S; Wientjes, M Guillaume; Couto, Jason; Couto, Guillermo

    2014-01-01

    Although conventional treatment of dogs with osteosarcoma (OSA) by amputation and chemotherapy results in reported survival times (STs) of 262-413 days, no major improvements in STs have occurred in the past 2 decades. Suramin is a polysulfonated napthylurea, which at noncytotoxic concentrations in vitro, increases tumor sensitivity to chemotherapy, including doxorubicin. The study authors evaluated the combination of noncytotoxic suramin and doxorubicin after amputation in dogs with OSA. The hypothesis was that treatment of dogs with appendicular OSA with amputation, adjuvant doxorubicin, and noncytotoxic suramin would be well tolerated and result in STs at least comparable to those of doxorubicin alone. Forty-seven dogs received 6.75 mg/kg of suramin IV followed by 30 mg/m(2) of doxorubicin IV 4 hr later. Treatment was repeated q 2 wk for five doses. The median disease free time (DFI) was 203 days (range, 42-1,580+ days) and the median ST for all dogs was 369 days (range, 92-1,616+ days). There was no statistical difference in ST and DFI between greyhounds and nonngreyhounds. Adjuvant doxorubicin and noncytotoxic suramin was well tolerated in dogs with OSA following amputation. Additional studies are needed to determine if this combination treatment protocol provides additional clinical benefit compared with doxorubicin alone.

  5. Adjuvant postoperative radiation therapy following simple hysterectomy and radical hysterectomy in stage IB cancer of the cervix: Analysis of risk factors and patterns of failure

    International Nuclear Information System (INIS)

    Kim, R.Y.; Weppelmann, B.; Sanford, S.P.; Salter, M.M.; Brascho, D.J.

    1986-01-01

    Between 1969 and 1980, 242 cases of stage IB cancer of the cervix were referred to the department of radiation oncology for curative radiation therapy. In 186 cases treatment was with radiation therapy alone. In 56 cases treatment included adjuvant postoperative radiation therapy; a minimum follow-up of 5 years has been carried out in this group. In 17 cases radiation therapy followed a simple hysterectomy for an unexpected stage IB cancer of the cervix. In 39 cases radiation therapy was given after a radical hysterectomy for stage IB cancer of the cervix because of positive margins and/or positive pelvic lymph nodes

  6. Adjuvant and salvage therapy following radical prostatectomy for prostate cancer: effect of combined transient androgen deprivation and irradiation

    International Nuclear Information System (INIS)

    Eulau, Stephen M.; Tate, David J.; Cox, Richard S.; Bagshaw, Malcolm A.; Hancock, Steven L.

    1996-01-01

    Purpose: Adjuvant and salvage irradiation have been shown to improve local control after radical prostatectomy for prostatic cancer in patients with high risk pathologic features, rising PSA, or evidence of local failure. Transient androgen deprivation combined with primary irradiation has resulted in improved local control and biochemical disease free survival in patients with locally advanced, unresected, prostate cancer. This retrospective study evaluates whether transient androgen blockade improves the outcome from post-prostatectomy irradiation given as either adjuvant or salvage therapy. Methods: From August, 1985 to December, 1995, 105 patients were treated with radiotherapy to the prostatic fossa following radical prostatectomy for adenocarcinoma of the prostate. No patient had clinically or radiographically evident distant disease. Median follow-up was 4.6 years from the date of surgery and 3.2 years from completion of radiotherapy. Findings at prostatectomy included capsular penetration in 38 patients, seminal vesicle involvement in 42 patients, lymph node involvement in 15 patients, and positive surgical margins in 70 patients. Treatment was administered as adjuvant therapy for high risk pathologic features in 39 patients, for persistent or rising PSA in 52 patients, or for clinically evident local recurrence in 14 patients. Of the 105 patients, 32 received combined androgen deprivation/radiotherapy and 73 received radiotherapy alone. Both groups received 60-70 Gy in 2 Gy daily fractions to the prostatic fossa. Selected patients with poor prognostic features received pelvic irradiation to a median dose of 50 Gy. Androgen deprivation typically consisted of Lupron and Flutamide for 4 to 6 months before, during, and in selected cases, after irradiation. No patients received maintenance androgen deprivation or underwent orchiectomy. Tumor stage, lymph node status, Gleason sum, and indications for treatment did not differ significantly between the two groups

  7. Efficacy and Safety Assessment of the Addition of Bevacizumab to Adjuvant Therapy Agents in Cancer Patients : A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    NARCIS (Netherlands)

    Ahmadizar, Fariba; Onland-Moret, N Charlotte; de Boer, Anthonius; Liu, Geoffrey; Maitland-van der Zee, Anke H

    2015-01-01

    AIM: To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients. METHODS & DESIGN/ RESULTS: PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials

  8. Efficacy and safety assessment of the addition of bevacizumab to adjuvant therapy agents in cancer patients: A systematic review and meta-analysis of randomized controlled trials

    NARCIS (Netherlands)

    Ahmadizar, Fariba; Onland-Moret, N. Charlotte; De Boer, Anthonius; Liu, Geoffrey; Maitland-Van Der Zee, Anke H.

    2015-01-01

    Aim: To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients. Methods & Design/Results: PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials

  9. Prognostic value of Bcl-2 in two independent populations of estrogen receptor positive breast cancer patients treated with adjuvant endocrine therapy

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Bjerre, Karsten; Giobbie-Hurder, Anita

    2012-01-01

    Estrogen receptor (ER) status is not an optimal marker for response to adjuvant endocrine therapy since approximately 30% of patients with ER-positive tumors eventually relapse. Bcl-2 is regulated by ER and may thus be considered as an indicator of ER activity and a candidate supplementary marker...

  10. Development and Validation of Consensus Contouring Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, Brian C. [Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Bosch, Walter R. [Washington University in St. Louis, St. Louis, Missouri (United States); Bahl, Amit [University Hospitals Bristol NHS Foundation Trust, Bristol (United Kingdom); Birtle, Alison J. [Royal Preston Hospital, Preston (United Kingdom); Breau, Rodney H. [University of Ottawa, Ottawa, Ontario (Canada); Challapalli, Amarnath [University Hospitals Bristol NHS Foundation Trust, Bristol (United Kingdom); Chang, Albert J. [University of California San Francisco, San Francisco, California (United States); Choudhury, Ananya [Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester (United Kingdom); The University of Manchester, Manchester Academic Heath Science Centre, Manchester (United Kingdom); Daneshmand, Sia [University of Southern California, Los Angeles, California (United States); El-Gayed, Ali [Saskatoon Cancer Centre, Saskatoon (Canada); Feldman, Adam [Massachusetts General Hospital, Boston, Massachusetts (United States); Finkelstein, Steven E. [Cancer Treatment Centers of America, Tulsa, Oklahoma (United States); Guzzo, Thomas J. [Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hilman, Serena [University Hospitals Bristol NHS Foundation Trust, Bristol (United Kingdom); Jani, Ashesh [Emory University, Atlanta, Georgia (United States); Malkowicz, S. Bruce [Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mantz, Constantine A. [21st Century Oncology, Scottsdale, Arizona (United States); 21st Century Oncology, Fort Myers, Florida (United States); Master, Viraj [Emory University, Atlanta, Georgia (United States); Mitra, Anita V. [University College London Hospital, London (United Kingdom); Murthy, Vedang [Tata Memorial Center, Mumbai (India); and others

    2016-09-01

    Purpose: To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials. Methods and Materials: We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ statistic. Results: The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral), whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. Conclusions: Consensus descriptions of CTVs and OARs were successfully developed and can be used in clinical trials of adjuvant radiation therapy for bladder cancer.

  11. Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer.

    Science.gov (United States)

    Dowsett, Mitch; Smith, Ian E; Ebbs, Steve R; Dixon, J Michael; Skene, Anthony; Griffith, Clive; Boeddinghaus, Irene; Salter, Janine; Detre, Simone; Hills, Margaret; Ashley, Susan; Francis, Stephen; Walsh, Geraldine; A'Hern, Roger

    2006-02-01

    The study of changes in proliferation as a marker of treatment benefit during presurgical endocrine treatment of breast cancer has become increasingly popular, particularly using the nuclear marker Ki67, and holds the potential for prioritizing new treatments for full clinical development. There are weakly significant relationships between Ki67 change and clinical response that differ according to data handling. In the neoadjuvant Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen trial, suppression of Ki67 at both 2 and 12 weeks was greater with the aromatase inhibitor anastrozole than with either tamoxifen or the combination of anastrozole and tamoxifen. We report here that absolute values of Ki67 after 2 weeks were also significantly lower with anastrozole than with tamoxifen and the combination. This indicates that it may be possible to make such comparisons using surgical samples only. We argue that these changes in proliferation and concurrent changes in apoptosis may be expected to be more predictive of adjuvant benefit from endocrine therapy than clinical response.

  12. Prognostic factors and long term results of neo adjuvant therapy followed by surgery in stage IIIA N2 non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Li Jing

    2009-01-01

    Full Text Available Background: Prognosis of stage IIIA N2 non-small cell lung cancer (NSCLC remains poor despite the changes in therapeutic strategies. Objectives: To assess long term results of neo adjuvant therapy followed by surgery for patients with stage IIIA N2 NSCLC and to analyze factors influencing survival. Materials and Methods: The methods adopted include: Retrospective review of medical records of 91 patients with stage IIIA N2 NSCLC, who received neo adjuvant therapy followed by surgery; collection of information on demographic information, staging procedure, preoperative therapy, clinical response, type of resection, pathologic response of tumor, status of lymph nodes and adjuvant chemotherapy; survival analysis by Kaplan-Meier and calculation of prognostic factors using log-rank and Cox regression model. Results: All patients received a platinum-based chemotherapy and 23 (29.1% had an associated radiotherapy. Eighty four patients underwent thoracotomy. Median survival was 26 months (95%CI, 22.6-30.8 months with three and five year survival rates of 31.6 and 20.9%, respectively. Prognostic factors for survival on univariate analysis was clinical response (P = 0.032, complete resection (P = 0.002, pathologic tumor response ( P < 0.001, and lymph nodal down staging (P = 0.001. Multivariate analyses identified complete resection, pathologic tumor response and lymph nodal down staging as independent prognostic factors. Conclusion: Survival of patients with stage IIIA N2 NSCLC who received neo adjuvant therapy is significantly influenced by clinical response, complete resection, pathologic tumor response, and lymph nodal down staging. These results can be helpful in guiding standard clinical practice and evaluating the outcome of neo adjuvant therapy followed by surgery in patients with stage IIIA N2 NSCLC.

  13. CD133 expression is not an independent prognostic factor in stage II and III colorectal cancer but may predict the better outcome in patients with adjuvant therapy

    International Nuclear Information System (INIS)

    Mia-Jan, Khalilullah; Jung, So Young; Kim, Ik-Yong; Oh, Sung Soo; Choi, EunHee; Chang, Sei Jin; Kang, Tae Young; Cho, Mee-Yon

    2013-01-01

    Cancer stem cells (CSCs) are notorious for their capacity of tumor progression, metastasis or resistance to chemo-radiotherapy. However, the undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not clear yet. We assessed 271 surgically-resected stage II and III primary CRCs with (171) and without (100) adjuvant therapy after surgery. CD133 expression was analyzed by immunohistochemical (IHC) staining and real-time RT-PCR. CD133 promoter methylation was quantified by pyrosequencing. The CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257) and inversely correlated with the promoter methylation (p=0.0001). CD133 was expressed more frequently in rectal cancer (p=0.0035), and in moderately differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not significantly correlated with overall survival (OS) (p=0.9689) as well as disease-free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly associated with better OS in patients with adjuvant therapy compared to those without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the patients with CD133- tumors did not show any significant difference of survival according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015). In stage II and III CRCs, CD133 IHC expression may signify the benefit for adjuvant therapy although it is not an independent prognostic factor

  14. Adjuvant bone-targeted therapy to prevent metastasis: lessons from the AZURE study.

    Science.gov (United States)

    Coleman, Robert E

    2012-09-01

    Bone-targeted treatments with bisphosphonates (e.g., zoledronic acid) and denosumab are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the 'vicious cycle' of growth factor and cytokine signalling between tumour and bone cells within the bone marrow microenvironment. In early stage breast cancer, treatment with zoledronic acid has shown improvements in disease-free and overall survival, notably in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease, treated with goserelin to suppress ovarian function. Other bisphosphonates such as clodronate may produce similar benefits. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments, but suggest that reproductive hormones are an important treatment modifier to take into account.

  15. Pegylated Liposomal Doxorubicin as Adjuvant Therapy for Stage I-III Operable Breast Cancer.

    Science.gov (United States)

    Lu, Yin-Che; Ou-Yang, F U; Hsieh, Chia-Ming; Chang, King-Jen; Chen, Dar-Ren; Tu, Chi-Wen; Wang, Hwei-Chung; Hou, Ming-Feng

    2016-01-01

    Conventional anthracyclines play an essential role for the treatment of breast cancer and have potent cytotoxic activity, but are associated with severe toxicity. In metastatic breast cancer, pegylated liposomal doxorubicin (PLD) is a formulation with efficacy similar to conventional doxorubicin but with reduced toxicity. This multicenter study evaluated the efficacy and safety of PLD-based adjuvant chemotherapy for women with stage I-III operable breast cancer. One hundred and eighty women with stage I-III breast cancer who received PLD-based adjuvant chemotherapy at six different Institutions in Taiwan from February 2002 to March 2008 were included and followed-up until April 2015. Treatment efficacy was determined by disease-free survival (DFS) rate and safety was evaluated by adverse events. The 5- and 10-year DFS rates were 76.3 and 72.6%, respectively. Univariate analysis revealed that tumor size >5 cm (p=0.045; hazard ratio=3.31) and stage III (hazard ratio=3.54; p=0.019) were each associated with shorter DFS. Only stage III (hazard ratio=5.60; p=0.018) retained statistical significance with regard to DFS in the multivariate analysis. Grade 3/4 hematological toxicity was neutropenia (n=13; 7.2%). The women receiving PLD had low-grade 3 or 4 nausea/vomiting, mucositis, and alopecia. Grade 3 hand-foot syndrome occurred in three patients (1.7%). PLD could be considered an effective and safe alternative to conventional anthracyclines in the treatment of stage I-III operable breast cancer. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Adjuvant neutron therapy in complex treatment of patients with locally advanced breast cancer

    Science.gov (United States)

    Lisin, V. A.; Velikaya, V. V.; Startseva, Zh. A.; Popova, N. O.; Goldberg, V. E.

    2017-09-01

    The study included 128 patients with stage T2-4N0-3M0 locally advanced breast cancer. All patients were divided into two groups. Group I (study group) consisted of 68 patients, who received neutron therapy, and group II (control group) comprised 60 patients, who received electron beam therapy. Neutron therapy was well tolerated by the patients and 1-2 grade radiation skin reactions were the most common. Neutron therapy was shown to be effective in multimodality treatment of the patients with locally advanced breast cancer. The 8-year recurrence-free survival rate in the patients with locally advanced breast cancer was 94.5 ± 4.1% after neutron therapy and 81.4 ± 5.9% after electron beam therapy (p = 0.05).

  17. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  18. [Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?].

    Science.gov (United States)

    Gómez, Ana M; Jarabo, José Ramón; Fernandez, Cristina; Calatayud, Joaquín; Fernández, Elena; Torres, Antonio J; Balibrea, José L; Hernando, Florentino

    2014-04-01

    Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

  19. Does Adjuvant Radiation Therapy Improve Outcomes In pT1-3N0 Oral Cavity Cancer With Tumor-Free Margins and Perineural Invasion?

    International Nuclear Information System (INIS)

    Liao, C.-T.; Chang, J.T.-C.; Wang, H.-M.; Ng, S.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2008-01-01

    Purpose: The criteria for administration of adjuvant radiation therapy (RT) in oral cavity squamous cell carcinoma (OSCC) remain controversial, and it is unclear whether patients with pT1-3N0 disease benefit from adjuvant radiation in the presence of free margins and perineural invasion. The goal of this report was to determine whether this group would benefit from adjuvant radiation therapy in terms of 5-year local control rate and overall survival rate. Methods and Materials: We retrospectively reviewed our case records from January 1996 to May 2005. In all, 460 pT1-3N0 OSCC patients had tumor-free margins, of whom 68 had perineural invasion. Postoperative adjuvant RT was performed in patients with pT4 tumors, positive lymph nodes, or close margins (≤4 mm). In addition, selected OSCC patients with large pT3 tumors or perineural invasion received postoperative adjuvant RT. Local control and overall survival rates were plotted by Kaplan-Meier analysis. Results: There were no significant differences in 5-year local control (p 0.1936) and overall survival (p = 0.5580) rates between patients with perineural invasion compared with those without. Among patients with perineural invasion, the addition of adjuvant radiotherapy did not significantly alter the 5-year local control rate (p = 0.3170) or the overall survival rate (p = 0.0935). Conclusion: Altogether, these data seem to indicate that radical surgical resection alone should be considered a sufficient treatment for OSCC patients with pT1-3N0 disease, even in the presence of perineural invasion

  20. Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy.

    Science.gov (United States)

    Kapewangolo, Petrina; Omolo, Justin J; Fonteh, Pascaline; Kandawa-Schulz, Martha; Meyer, Debra

    2017-10-13

    Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of infected patients on combination antiretroviral therapy (cART). The mechanism of viral reactivation was determined through the compound's effect on cytokine production, histone deacetylase (HDAC) inhibition, and protein kinase C (PKC) activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6 a ,6 b ,11,12,14 b -hexamethyl-1,2,3,4,6,6 a ,6 b ,7,8,8 a ,9,10,11,12,12 a ,14,14 a ,14 b -octadecahydropicene-4,8 a -dicarboxylic acid (HHODC), significantly ( p HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL)-2, IL-6, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here.

  1. Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Petrina Kapewangolo

    2017-10-01

    Full Text Available Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs of infected patients on combination antiretroviral therapy (cART. The mechanism of viral reactivation was determined through the compound’s effect on cytokine production, histone deacetylase (HDAC inhibition, and protein kinase C (PKC activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8a-dicarboxylic acid (HHODC, significantly (p < 0.05 induced HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL-2, IL-6, tumour necrosis factor (TNF-α, and interferon (IFN-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here.

  2. Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

    2017-05-02

    Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

  3. The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial.

    Science.gov (United States)

    Pinsornsak, Piya; Niempoog, Sunyarn

    2012-01-01

    Nonsteroidal anti-inflammatory Drugs (NSAIDs) is one of the most commonly use medication for treatment of knee osteoarthritis which has the analgesic and anti-inflammation by inhibition of prostaglandin synthesis via COX-1 and COX-2 isoenzyme. The problem of prolong using NSAIDs has side effect on kidney, liver and GI system. Curcumin longa extract Curcumin) is the Asian herbal medicine that has the anti-inflammatory effect by down regulate activation of NF-kappaB and proinflammatory cytokines such as Tumor Necrotic Factor-alpha, Interleukin-1, Interleukin-8, and Nitric Oxide Syntase. Many research data had advocate for the combination therapy which can increase safety and efficacy with less side effect compare with monotherapy regimen especially when the medicine has the different mechanism of action. The present study is the double blind prospective randomized control trial to evaluate the efficacy of curcumin as an adjuvant therapy of diclofenac in primary knee osteoarthritis. 44 patients were randomized to take NSAIDs (diclofenac) 75 mg/d with placebo and the other 44 took NSAIDs (diclofenac) 75 mg/d with curcumin 1,000 mg/d for 3 months. The authors evaluated the Visual Analog Scale (VAS) for pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) every month for 3 months. At the end of study 36 patients were completed for the first group and 37 for the study group. There was no difference in VAS [p-value = 0.923 (F = 0.009)]. The KOOS was analyzed in 5 categories symptom, pain, function in daily living, function in sport and recreation and knee related quality of life. The curcumin with diclofenac group had tendency to be better in Pain and Function in daily living, but there were no statistic different in all group [p-value = 0.412 (F = 0.683), p-value = 0.814 (F = 0.056), p-value = 0.446 (F = 0.589), p-value = 0.224 (F = 1.511) and p-value = 0.938 (F = 0.006)]. In conclusion, the adjuvant therapy ofcurcumin with diclofenac has the potential beneficial

  4. Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

    Science.gov (United States)

    Kuranishi, Fumito; Ohno, Tadao

    2013-06-04

    Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

  5. Tumor specific HMG-CoA reductase expression in primary pre-menopausal breast cancer predicts response to tamoxifen

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2011-01-31

    Abstract Introduction We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. Methods HMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response. Results HMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive\\/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as

  6. New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma

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    Hor-Yue Tan

    2016-08-01

    Full Text Available For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC cell lines and human umbilical vein endothelial cells (HUVEC were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC.

  7. Genital tuberculosis in a tamoxifen-treated postmenopausal woman with breast cancer and bloody vaginal discharge

    Directory of Open Access Journals (Sweden)

    Maraki Sofia

    2006-09-01

    Full Text Available Abstract Background Female genital tuberculosis is an uncommon disease that is rarely diagnosed in developed countries. Case presentation A 61-year-old postmenopausal woman who had undergone surgery and treated with adjuvant chemotherapy for infiltrating ductal carcinoma of the breast five years ago, presented with bloody vaginal discharge, fatigue, weight loss, and low grade fevers at night for two months. Histological examination of the endometrium, done based on the suspicion of a second primary cancer due to the tamoxifen therapy, revealed a granulomatous reaction. Liquid and solid mycobacterial cultures of the tissues were performed. Although the acid fast staining was negative, the liquid culture was positive for Mycobacterium tuberculosis. Involvement of other systems was not detected. The patient was treated with a three-drug antituberculosis regimen for 9 months and recovered fully. Conclusion Female genital tuberculosis is a rare but curable disease that should be included in the differential diagnosis of women with menstrual problems. Early diagnosis is important and may prevent unnecessary invasive procedures for the patient.

  8. POSSIBILITY OF NATURAL RAW MATERIALS USE IN THE FORMULATION OF ADJUVANT THERAPY OF TUBERCULOSIS: EXPERIENCE OF FOLK MEDICINE, MODERN STATE OF STUDIES

    Directory of Open Access Journals (Sweden)

    M. E. Kim

    2017-01-01

    Full Text Available The signs of growth in the prevalence of multidrug-resistant tuberculosis, low effectiveness of therapy indicate the urgent need to solve problems aimed at the improvement of the effectiveness of treatment: the reduction of toxicity and side effects of anti-tuberculosis drugs, the provision of good tolerability and continuity of chemotherapy; the removal of symptoms of intoxication associated with the action of the pathogen on the body, the improvement of the quality of life of patients during therapy and remission.The aim of the investigation is to study the data of folk medicine, scientific research data concerning the use of raw materials of natural (vegetable, animal and mineral origin in the adjuvant therapy of tuberculosis.Materials and methods. The study was carried out using information retrieval and library databases (PubMed, eLIBRARY, Cyberleninka, technical information of manufacturers of dietary supplements to food, as well as site materials dedicated to the use of vegetable, animal and mineral raw materials in folk medicine.Results and discussion. The adjuvant therapy of tuberculosis includes remedies of natural origin: vegetable, animal and mineral ones. According to the research data, the use of phytotherapy is aimed at enhancing diuresis, which ensures the elimination of toxic substances and their metabolites, as well as the decrease of the overall level of toxins; the strengthening of the body’s antioxidant defense, and liver specificity, the compensation for the increased consumption of vitamins, amino acids and microelements by the liver, which actively metabolizes xenobiotics, as well as the increase of the body’s overall resistance. A long-term benefit of using natural mineral raw materials in adjuvant therapy of tuberculosis is also observed.Conclusion. Thus, adjuvant therapy of tuberculosis includes the use of raw materials of natural (vegetable, animal and mineral origin, the effectiveness of which is confirmed by

  9. Effects of 13- cis-retinoic acid on the tamoxifen induced uterine histological changes in the rabbit

    International Nuclear Information System (INIS)

    Hamid, S.; Minhas, L.A.; Khan, M.Y.

    2013-01-01

    Objective: To study the effects of 13-cis-retinoic acid on the tamoxifen induced uterine histological changes in the rabbit. Study Design: Experimental - randomized controlled trial. Place and Duration of study: The study was conducted for 4 months at the department of Anatomy, Army Medical College and National Institute of Health in 2007. Material and Methods: The animals were randomly divided into three groups, a control group A, and two experimental groups B and C, consisting of thirty rabbits each. The experimental groups were treated with tamoxifen only and tamoxifen plus retinoic acid, respectively. The animals were sacrificed after three months. The uteri were then processed for paraffin embedding. Sections were then assessed for the luminal epithelial height, endometrial area and percentage of mitotic figures. Results: The results obtained were suggestive of uterine proliferation by tamoxifen. The adjuvant administration of 13-cis-retinoic acid produced a statistically significant (p = 0.002) inhibitory effect on the tamoxifen induced increase in the area of endometrium, whereas no significant suppressive effect of this drug has been observed on the other parameters when compared with Group B. Conclusion: 13-cis Retinoic acid has not shown a significant role in the reversal of tamoxifen induced changes in the uterine tissue after a short term administration of three months. (author)

  10. Adjuvant therapy of Dukes' C colon cancer by intra-arterial P-32 colloid for internal radiation therapy of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Grady, E.D.

    1984-09-01

    To prevent probable occult metastatic liver cancer from progressing to clinical disease, the author used internal radiation therapy as an effective adjuvant to surgical excision of primary Dukes' C colonic cancer. A calculated radiation dose of 5000 rads was delivered to the liver by injecting radioactive 32-P chromic phosphate colloid through the superior mesenteric and celiac arteries. When this was done, the colloid passed through the intestines and was mixed thoroughly with the blood and delivered to the liver by the portal vein. The Kupffer cells in the liver trapped the colloid, and a minimum amount passed through the liver and got into the general circulation. This kept the amount of colloid deposited in the bone marrow to a minimum. In a phase-I pilot study in which nine patients were treated, no serious side effects were noted. In eight patients, the liver has remained free of cancer for more than 1 year.

  11. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma.

    Directory of Open Access Journals (Sweden)

    Mohammed G Abdelwahab

    Full Text Available INTRODUCTION: The ketogenic diet (KD is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas. METHODS: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging. RESULTS: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173 and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001. Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days. CONCLUSIONS: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

  12. High frequency of brain metastases after adjuvant therapy for high-risk melanoma.

    Science.gov (United States)

    Samlowski, Wolfram E; Moon, James; Witter, Merle; Atkins, Michael B; Kirkwood, John M; Othus, Megan; Ribas, Antoni; Sondak, Vernon K; Flaherty, Lawrence E

    2017-11-01

    The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  13. Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial

    International Nuclear Information System (INIS)

    Miller, Robert C.; Sargent, Daniel J.; Martenson, James A.; Macdonald, John S.; Haller, Daniel; Mayer, Robert J.; Gunderson, Leonard L.; Rich, Tyvin A.; Cha, Stephen S.; O'Connell, Michael J.

    2002-01-01

    Purpose: During adjuvant radiotherapy (RT) for rectal cancer, patients receiving 5-fluorouracil (5-FU) by protracted venous infusion have a higher risk of diarrhea than have patients receiving bolus 5-FU. Toxicity from a previously reported randomized clinical trial was analyzed to quantify the difference in this risk. Additionally, the persistence of diarrhea after RT was analyzed. Methods and Materials: A total of 656 patients were eligible. Patients with T3-4 N0-2 M0 or T1-2 N1-2 M0 resected, high-risk rectal cancer were randomly allocated to receive 5-FU by either protracted venous infusion or bolus during RT (50.4-54.0 Gy). Two cycles of bolus 5-FU were given before and after RT. One-half of the first 445 patients were also randomly allocated to receive lomustine in conjunction with the bolus 5-FU. The incidence and severity of diarrhea in relation to patient and treatment characteristics were evaluated. Results: The rate of diarrhea was significantly greater in patients receiving 5-FU by protracted venous infusion than in patients receiving bolus 5-FU; the difference was most pronounced for Grade 3 (severe) diarrhea (21% versus 13%, p=0.007). The incidence and magnitude of diarrhea before and after RT were similar. Patients treated with an anterior resection had a higher rate of severe or life-threatening diarrhea than did patients treated with an abdominoperineal resection (31% vs. 12%, p<0.001). Conclusions: During pelvic RT, patients who receive 5-FU by protracted venous infusion rather than by bolus have a higher risk of severe or life-threatening diarrhea during RT. This risk does not appear to persist during chemotherapy after completion of pelvic RT

  14. [Can the efficacy of behavioral and cognitive therapy for obsessive compulsive disorder be augmented by innovative computerized adjuvant?

    Science.gov (United States)

    Morgiève, M; N'Diaye, K; Clair, A-H; Pelissolo, A; Mallet, L

    2016-10-01

    usability. The clinical improvement was associated with a reduction of the task-induced anxiety (r=0.42, Pimprovement (r=0.82, Ptool may provide a well-accepted therapeutic adjuvant even though it doesn't improve the therapeutic effect. Using a personalized symptom-provocation task reveals the parallel evolution of symptoms and neurobehavioral markers through CBT. Despite the difficulty of improving an evidence-based therapy, mid-therapy results call for investigating the possible adjustments of treatment strategies at an early stage. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  15. Cognitive function after adjuvant treatment for early breast cancer

    DEFF Research Database (Denmark)

    Debess, Jeanne; Riis, Jens Østergaard; Engebjerg, Malene Cramer

    2010-01-01

    The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged ... chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before...... themselves as impaired at 6 months. Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients....

  16. Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

    Science.gov (United States)

    Bluethmann, Shirley M; Alfano, Catherine M; Clapp, Jonathan D; Luta, George; Small, Brent J; Hurria, Arti; Cohen, Harvey J; Sugarman, Steven; B Muss, Hyman; Isaacs, Claudine; Mandelblatt, Jeanne S

    2017-10-01

    To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p cognition was not related to discontinuation in the other periods. Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

  17. Aerobic Exercise as an Adjuvant to Aphasia Therapy: Theory, Preliminary Findings, and Future Directions.

    Science.gov (United States)

    Harnish, Stacy M; Rodriguez, Amy D; Blackett, Deena Schwen; Gregory, Christopher; Seeds, Lauren; Boatright, Jeffrey H; Crosson, Bruce

    2018-01-01

    This study investigated whether participation in aerobic exercise enhances the effects of aphasia therapy, and the degree to which basal serum brain-derived neurotropic factor (BDNF) concentrations fluctuate after the beginning of aerobic exercise or stretching activities in individuals with poststroke aphasia. The study used a single-subject, multiple-baseline design. Seven individuals with chronic poststroke aphasia participated in 2 Blocks of aphasia therapy: aphasia therapy alone (Block 1), followed by aphasia therapy with the addition of aerobic activity via bicycle ergometer (n = 5) or stretching (n = 2) (Block 2). Serum BDNF concentrations from blood draws were analyzed in 4 participants who exercised and in 1 participant who stretched. Three of the five exercise participants demonstrated larger Tau-U effects when aphasia therapy was paired with aerobic exercise, whereas 1 of the 2 stretching participants demonstrated a larger effect size when aphasia therapy was paired with stretching. Group-level comparisons revealed a greater overall increase in effect size in the aerobic exercise group, as indicated by differences in Tau-U weighted means. BDNF data showed that all 4 exercise participants demonstrated a decrease in BDNF concentrations during the first 6 weeks of exercise and an increase in BDNF levels near or at baseline during the last 6 weeks of exercise. The stretching participant did not show the same pattern. Additional research is needed to understand the mechanism of effect and to identify the factors that mediate response to exercise interventions, specifically the optimal dose of exercise and timing of language intervention with exercise. ClinicalTrials.gov identifier: NCT01113879. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  18. Timing of Surgery and the Role of Adjuvant Radiation Therapy in Ewing Sarcoma of the Chest Wall: A Single Institution Experience

    Science.gov (United States)

    Denbo, Jason W.; Orr, W. Shannon; Wu, Yanan; Wu, Jianrong; Billups, Catherine A.; Navid, Fariba; Rao, Bhaskar; Davidoff, Andrew M.; Krasin, Matthew J.

    2012-01-01

    Introduction Ewing sarcoma (ES) is the most common chest wall malignancy in adolescents. Current therapy incorporates chemotherapy to treat systemic disease and radiation to assist with local control. We sought to evaluate the timing of surgery and role of adjuvant radiation. Methods We reviewed the SJCRH chest wall ES experience from 1979-2009. Patient demographics, tumor characteristics, treatment variables, and outcomes were analyzed with respect to timing of surgery and use of adjuvant radiation. Results Our cohort consisted of 36 patients with chest wall ES; median follow-up of 14.2 years and 15-year estimate of overall survival (OS) was 66%. In patients with localized disease, the timing of surgery (up-front versus delayed) did not impact margin negativity or the use of adjuvant radiation, but did decrease the extent of chest wall resection. When considering radiation in patients with localized disease, we found that patients who did not receive radiation had smaller tumor size (median, 6 versus 10cm) (p=0.04), and were more likely to have had negative margins (p=0.01) than patients who received adjuvant radiation. One patient in each group developed a locoregional recurrence. The 15-year estimated of OS for patients who received adjuvant radiation was 80% versus 100% for those who did not. Conclusion Delayed surgery decreased the extent of chest wall resection and helped define a patient population with favorable tumor biology. Patients with complete pathologic responses to chemotherapy, and those with tumors < 8cm and negative surgical margins may be spared adjuvant radiation without any decrement in OS. PMID:22752372

  19. The role of hormonal ovarian ablation in adjuvant treatment of premenopausal breast cancer

    Directory of Open Access Journals (Sweden)

    Murtezani Zafir

    2011-01-01

    Full Text Available Introduction. Breast cancer is the most frequent malignant disease in women with about 25% compared to all malignant tumours. Chemotherapy, antiestrogen and ovarian ablation/ supression present effective adjuvant approach for premenopausal women diagnosed with hormonal depended, operable breast cancer. Objective. To evaluate benefits of combined chemo/hormonal therapy that is undutiful, but optimal application has not yet been clearly determined. Methods. Thirty-six women were divided into three therapy groups. The first group (13 women was treated with six cycles of adjuvant FAC chemotherapy followed by regular check-ups; the second group (13 women after six cycles of adjuvant FAC chemotherapy continued treatment with a two-year application of goserelin given by subcutaneous injections (FAC-Z; the third group (10 women, after six cycles of adjuvant FAC chemotherapy continued with once per month application of gorselin for two years and a daily application of 20 mg tamoxifen for five years (FAC-Z-T. The length of overall disease free period and survival were analyzed in all three groups. Results. The benefit of LH-RH analogues in premenopausal women with hormone-dependent breast cancer was found to be low, and probably limited to smaller subgroups of patients, possibly such as those with either both steroid receptors positive (ER and PR or those with an extremely high level of steroid receptors. In our paper, analyses of such subgroups could not been performed due to a small sample of patients. The effect of therapy is better in patients, who developed amenorrhoea, regardless of the type of later hormonal therapy. Conclusion. Ovarial ablation, whatever the method, should be probably applied as early as possible within the treatment of early breast cancer, especially in patients in whom chemotherapy induced amenorrhoea is not expected, i.e. in very young female patients.

  20. Antimicrobial Photodynamic Therapy as a Co-adjuvant in Endodontic Treatment of Deciduous Teeth: Case Series.

    Science.gov (United States)

    Okamoto, Camila Basilio; Motta, Lara Jasinski; Prates, Renato Araujo; da Mota, Ana Carolina Costa; Gonçalves, Marcela Leticia Leal; Horliana, Anna Carolina Ratto Tempestini; Mesquita Ferrari, Raquel Agnelli; Fernandes, Kristianne Porta Santos; Bussadori, Sandra Kalil

    2018-02-08

    To assure the success of endodontic treatment, the root canal must be completely decontaminated. Thus, some methods have been researched in an attempt to effectively eliminate microorganisms from the interior of the root canal system. Among them, is conventional endodontic therapy in conjunction with photodynamic therapy (PDT). Five anterior deciduous teeth were treated endodontically with the conventional technique and PDT. For PDT, 0.005% methylene blue was used as a photosensitizer and a 660nm laser. After the conventional endodontic therapy, the photosensitizer was applied inside the root canal, 3 minutes of pre-irradiation time and then the laser was applied for 40s with an energy of 4J. Afterwards, the canal was irrigated with saline solution and the sealing material of the root canal was placed. The microbiological analysis of the samples were collected before and after the treatments were performed. Observing the results obtained in this case series,which showed a bacterial reduction from 37.57% to 100%, and the clear difficulty in the success of endodontic treatment of deciduous teeth, antimicrobial photodynamic therapy can be considered an alternative of easy application, and that does not generate microbial resistance, to act as a support in the decontamination of the root canals. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis

    Czech Academy of Sciences Publication Activity Database

    Kuncírová, V.; Poništ, S.; Mihalová, D.; Dráfi, F.; Nosáľ, R.; Acquaviva, A.; Gardi, C.; Harmatha, Juraj; Hrádková, I.; Bauerová, K.

    2014-01-01

    Roč. 28, č. 6 (2014), s. 616-626 ISSN 0767-3981 Institutional support: RVO:61388963 Keywords : arthritis * inflammation * oxidative stress * combination therapy * methotrexate * N-feruloylserotonin Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.121, year: 2014

  2. TERT promoter mutations contribute to IDH mutations in predicting differential responses to adjuvant therapies in WHO grade II and III diffuse gliomas.

    Science.gov (United States)

    Zhang, Zhen-Yu; Chan, Aden Ka-Yin; Ding, Xiao-Jie; Qin, Zhi-Yong; Hong, Christopher S; Chen, Ling-Chao; Zhang, Xin; Zhao, Fang-Ping; Wang, Yin; Wang, Yang; Zhou, Liang-Fu; Zhuang, Zhengping; Ng, Ho-Keung; Yan, Hai; Yao, Yu; Mao, Ying

    2015-09-22

    IDH mutations frequently occur in WHO grade II and III diffuse gliomas and have favorable prognosis compared to wild-type tumors. However, whether IDH mutations in WHO grade II and II diffuse gliomas predict enhanced sensitivity to adjuvant radiation (RT) or chemotherapy (CHT) is still being debated. Recent studies have identified recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) in gliomas. We previously demonstrated that TERT promoter mutations may be promising biomarkers in glioma survival prognostication when combined with IDH mutations. This study analyzed IDH and TERT promoter mutations in 295 WHO grade II and III diffuse gliomas treated with or without adjuvant therapies to explore their impact on the sensitivity of tumors to genotoxic therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter mutations were found in 112 (38%) patients. In multivariate analysis, IDH mutations (p IDH and TERT promoter mutations were not significant prognostic factors in patients who did not receive genotoxic therapies. Adjuvant RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026) in IDH mutated WHO grade II and III diffuse gliomas but not in IDH wild-type group. Univariate and multivariate analyses demonstrated TERT promoter mutations further stratified IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to genotoxic therapies. Adjuvant RT and CHT were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data demonstrated that IDH mutated WHO grade II and III diffuse gliomas had better PFS and OS than their IDH wild-type counterparts when genotoxic therapies were administered after surgery. Importantly, we also found that TERT promoter mutations further stratify IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to

  3. ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen

    Directory of Open Access Journals (Sweden)

    Sensorn I

    2016-04-01

    Full Text Available Insee Sensorn,1,* Chonlaphat Sukasem,2,* Ekaphop Sirachainan,3 Montri Chamnanphon,2 Ekawat Pasomsub,4 Narumol Trachu,5 Porntip Supavilai,1 Darawan Pinthong,1 Sansanee Wongwaisayawan6 1Department of Pharmacology, Faculty of Science, Mahidol University, 2Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 3Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 4Division of Virology, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 5Research Center, Faculty of Medicine, Ramathibodi Hospital, 6Division of Anatomical Pathology, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand *These authors contributed equally to this work Background: Genetic polymorphisms of drug-metabolizing enzymes and transporters have been extensively studied with regard to tamoxifen treatment outcomes. However, the results are inconclusive. Analysis of organ-specific metastasis may reveal the association of these pharmacogenetic factors. The aim of this study is to investigate the impact of CYP3A5, CYP2D6, ABCB1, and ABCC2 polymorphisms on the risk of all distant and organ-specific metastases in Thai patients who received tamoxifen adjuvant therapy. Methods: Genomic DNA was extracted from blood samples of 73 patients with breast cancer who received tamoxifen adjuvant therapy. CYP3A5 (6986A>G, CYP2D6 (100C>T, ABCB1 (3435C>T, and ABCC2 (-24C>T were genotyped using allelic discrimination real-time polymerase chain reaction assays. The impacts of prognostic clinical factors and genetic variants on disease-free survival were analyzed using the Kaplan–Meier method and Cox regression analysis. Results: In the univariate analysis, primary tumor size >5 cm was significantly associated with increased risk of distant metastasis (P=0

  4. A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer.

    Science.gov (United States)

    Kristeleit, Rebecca; Davidenko, Irina; Shirinkin, Vadim; El-Khouly, Fatima; Bondarenko, Igor; Goodheart, Michael J; Gorbunova, Vera; Penning, Carol A; Shi, Jack G; Liu, Xiangdong; Newton, Robert C; Zhao, Yufan; Maleski, Janet; Leopold, Lance; Schilder, Russell J

    2017-09-01

    Indoleamine 2,3-dioxygenase-1 (IDO1) is a key regulator of immune tolerance in ovarian cancer. This study investigated efficacy and safety of the IDO1 enzyme inhibitor epacadostat versus tamoxifen in patients with biochemical-only recurrence (CA-125 elevation) following complete remission after first-line chemotherapy for advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. In this open-label, phase 2 study (NCT01685255), patients were randomised 1:1 to epacadostat 600mg or tamoxifen 20mg twice daily for successive 28-day cycles and stratified by time since completion of first-line chemotherapy to first CA-125 elevation (3 to CA-125 response (Gynecologic Cancer InterGroup criteria), overall survival, safety, and tolerability. The study was terminated primarily due to slow accrual and lack of evidence of superiority. Median PFS was 3.75months for epacadostat (n=22) versus 5.56months for tamoxifen (n=20; HR, 1.34 [95% CI, 0.58-3.14]; P=0.54). Of evaluable patients, 1 (5.0%) epacadostat and 3 (15.8%) tamoxifen patients had confirmed CA-125 responses. The most common treatment-emergent adverse event was fatigue (epacadostat, 36.4%; tamoxifen, 40.0%). Immune-related adverse events, observed with epacadostat only, were primarily rash (18.2%) and pruritus (9.1%). Epacadostat pharmacokinetics/pharmacodynamics were consistent with its known mechanism of action. IDO1 expression was observed in 94% of archival tumour samples. This first report of immunotherapy evaluation in biochemical-only relapse ovarian cancer and of IDO1 inhibitor monotherapy in ovarian cancer found no significant difference in efficacy between epacadostat and tamoxifen. Epacadostat was generally well tolerated. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Adjuvant potential of virgin coconut oil extract on antiretroviral therapy-induced testicular toxicity: An ultrastructural study.

    Science.gov (United States)

    Ogedengbe, O O; Jegede, A I; Onanuga, I O; Offor, U; Peter, A I; Akang, E N; Naidu, E C S; Azu, O O

    2018-04-01

    The effects of Virgin coconut oil as an adjuvant to highly active antiretroviral therapy (HAART) were investigated on the testicular ultrastructure and biochemical markers in rats. Twenty male Sprague-Dawley rats, weighing 153-169 g were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (HAART+Virgin coconut oil 10 ml/kg) and D (Virgin coconut oil [VCO] 10 ml/kg). Testicular segments were evaluated using transmission electron microscopy. Serum was assayed for testosterone, luteinising hormone, follicle stimulating hormone and testicular tissue for malondialdehyde and glutathione. Ultrastructure of basement membrane (Bm), mitochondria and spermatocytes was normal in the control group. HAART-treated group showed significant increase (p coconut oil-treated group showed thinning of Bm with otherwise normal ultrastructural features of organelles. HAART-treated group showed significant increase (p coconut oil improved testicular morphology and reversed HAART-induced ultrastructural alterations. Further studies on putative mechanism are required. © 2017 Blackwell Verlag GmbH.

  6. Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy

    DEFF Research Database (Denmark)

    Eefsen, R L; Engelholm, L; Alpizar-Alpizar, W

    2015-01-01

    Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasm......Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase......-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis...... inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy...

  7. Expanded risk groups help determine which prostate radiotherapy sub-group may benefit from adjuvant androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Williams Scott G

    2008-04-01

    Full Text Available Abstract Purpose To assess whether an expanded (five level risk stratification system can be used to identify the sub-group of intermediate risk patients with prostate cancer who benefit from combining androgen deprivation therapy (ADT with external beam radiotherapy (EBRT. Materials and methods Using a previously validated 5-risk group schema, a prospective non-randomized data set of 1423 men treated at the British Columbia Cancer Agency was assessed for the primary end point of biochemical control (bNED with the RTOG-ASTRO "Phoenix" definition (lowest PSA to date + 2 ng/mL, both with and without adjuvant ADT. The median follow-up was 5 years. Results There was no bNED benefit for ADT in the low or low intermediate groups but there was a statistically significant bNED benefit in the high intermediate, high and extreme risk groups. The 5-year bNED rates with and without ADT were 70% and 73% respectively for the low intermediate group (p = non-significant and 72% and 58% respectively for the high intermediate group (p = 0.002. Conclusion There appears to be no advantage to ADT where the Gleason score is 6 or less and PSA is 15 or less. ADT is beneficial in patients treated to standard dose radiation with Gleason 6 disease and a PSA greater than 15 or where the Gleason score is 7 or higher.

  8. Role of adjuvant therapy in the treatment of helicobacter pylori infection in children

    Directory of Open Access Journals (Sweden)

    Gerasymenko O.N.

    2014-06-01

    Full Text Available The aim was to study the effect of combined probiotic containing Lactobacillus acidophilus, Bifidobacterium infantis, Enterococcus faecium, on H.pylori eradication efficacy in the treatment of children with chronic H.pylori- associated gastroduodenitis in the scheme of "triple" therapy of H.pylori eradication. Determination of total serum Ig M , A, G protein to Ag SagA H. pylori, breathing "Helik" test, rapid urease "Helpil" test ; that of concentration of serum sCD14 was conducted. The study group included 20 children who received standard "triple" eradication therapy for 7 days and 1 caps. of probiotic 3 times a day for 4 weeks, control group (20 children – who received only standard eradication therapy. It is shown that combined use of probiotics in the treatment of Helicobacter pylori infection enhances effectiveness of eradication of H.pylori. In the basis of action of probiotic strains of the drug is an anti-inflammatory effect mediated by the impact on non-specific mechanisms of innate immunity, provided by molecular mechanism responsible for induction of sCD14 synthesis.

  9. Racial differences in receipt of adjuvant hormonal therapy among Medicaid enrollees in South Carolina diagnosed with breast cancer

    Science.gov (United States)

    Felder, Tisha M.; Do, D. Phuong; Lu, Z. Kevin; Lal, Lincy S.; Heiney, Sue P.; Bennett, Charles L.

    2016-01-01

    Purpose Several factors contribute to the pervasive Black-White disparity in breast cancer mortality in the U.S., such as tumor biology, access to care and treatments received including adjuvant hormonal therapy (AHT), which significantly improves survival for hormone-receptor positive breast cancers (HR+). We analyzed South Carolina Central Cancer Registry-Medicaid linked data to determine if, in an equal access health care system, racial differences in the receipt of AHT exist. Methods We evaluated 494 study-eligible, Black (n=255) and White women (n=269) who were under 65 years old and diagnosed with stages I–III, HR+ breast cancers between 2004 and 2007. Bivariate and multivariate analyses were conducted to assess receipt of ≥ 1 AHT prescriptions at any point in time following (ever-use) or within 12 months of (early-use) breast cancer diagnosis. Results Seventy-two percent of the participants were ever-users (70% Black, 74% White) and 68% were early-users (65% Black, 71% White) of AHT. Neither ever-use (adjusted OR (AOR)=0.75, 95% CI: 0.48–1.17) nor early-use (AOR=0.70, 95% CI: 0.46–1.06) of AHT differed by race. However, receipt of other breast cancer-specific treatments was independently associated with ever-use and early-use of AHT [ever-use: receipt of surgery (AOR= 2.15, 95% CI: 1.35–3.44); chemotherapy (AOR=1.97, 95% CI: 1.22–3.20); radiation (AOR=2.33, 95% CI: 1.50–3.63); early-use: receipt of surgery (AOR=2.03, 95% CI: 1.30–3.17); chemotherapy (AOR=1.90, 95% CI: 1.20–3.03); radiation (AOR=1.73, 95% CI: 1.14–2.63)]. Conclusions No racial variations in use of AHT among women with HR+ breast cancers insured by Medicaid in South Carolina were identified, but overall rates of AHT use by these women is low. Strategies to improve overall use of AHT should include targeting breast cancer patients who do not receive adjuvant chemotherapy and/or radiation. PMID:27120468

  10. A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6

    DEFF Research Database (Denmark)

    Iversen, P; Tammela, T L J; Vaage, S

    2002-01-01

    To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer.......To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer....

  11. Safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin and 5-fluorouracil after mesorectal excision with lateral pelvic lymph node dissection for stage iii lower rectal cancer.

    Science.gov (United States)

    Iwasa, Satoru; Souda, Hiroaki; Yamazaki, Kentaro; Takahari, Daisuke; Miyamoto, Yuji; Takii, Yasumasa; Ikeda, Satoshi; Hamaguchi, Tetsuya; Kanemitsu, Yukihide; Shimada, Yasuhiro

    2015-03-01

    Preoperative chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for stage III lower rectal cancer worldwide. However, in Japan, the standard treatment is TME with lateral pelvic lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5-fluorouracil (modified FOLFOX6) after TME with LPLD. This retrospective study included 33 patients who received modified FOLFOX6 after TME with LPLD for stage III lower rectal cancer. The overall completion rate of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was observed in eight patients (24%). Sensory neuropathy was observed in 32 patients (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate was 45% at 3 years. Adjuvant modified FOLFOX6 was feasible in patients with stage III lower rectal cancer after TME with LPLD. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer

    DEFF Research Database (Denmark)

    Swanton, Charles; Szallasi, Zoltan Imre; Brenton, James D.

    2008-01-01

    The widespread introduction of high throughput RNA interference screening technology has revealed tumour drug sensitivity pathways to common cytotoxics such as paclitaxel, doxorubicin and 5-fluorouracil, targeted agents such as trastuzumab and inhibitors of AKT and Poly(ADP-ribose) polymerase (PARP......) as well as endocrine therapies such as tamoxifen. Given the limited power of microarray signatures to predict therapeutic response in associative studies of small clinical trial cohorts, the use of functional genomic data combined with expression or sequence analysis of genes and microRNAs implicated...... in drug response in human tumours may provide a more robust method to guide adjuvant treatment strategies in breast cancer that are transferable across different expression platforms and patient cohorts....

  13. Role of Concurrent Systemic Therapy with Adjuvant Radiation Therapy for Locally Advanced Cutaneous Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Goyal, Uma; Prabhakar, Nitin K; Davuluri, Rajayogesh; Morrison, Christopher M; Yi, Sun K

    2017-10-19

    Objective To evaluate the role of concurrent systemic therapy to postoperative radiation therapy (RT) for locally advanced cutaneous head and neck squamous cell carcinoma (LA-cHNSCC). Materials and methods A retrospective study of 32 patients with LA-cHNSCC receiving postoperative RT with and without systemic therapy was conducted. Patients with LA-cHNSCC after surgical resection with one or more high risk features were evaluated. Local regional control (LRC), distant control (DC), and acute and late toxicities were evaluated with Fisher exact tests. Progression-free survival (PFS) and overall survival (OS) were evaluated utilizing Kaplan Meier and log-rank analyses. Univariate Cox proportional hazard analyses were used to examine patient, disease, and treatment-related factors with OS and PFS. Results While comparing patients receiving RT with systemic therapy (n = 14) vs RT alone (n = 18), LRC was 92.9% vs 72.2% (p = 0.20), DC 92.9% vs 94.4% (p = 1.0), median PFS 17.7 months vs 34.4 months (p = 0.48), and median OS 20.9 months vs 34.4 months (p = 0.03), respectively. On univariate analyses, use of concurrent systemic therapy was associated with an increased risk of death with an HR of 3.5 [95% confidence interval (CI): 1.04 - 11.6] (p = 0.04), while patients treated for recurrent disease who had previously treated superficial primaries had improved OS with an HR of 0.10 [95% CI: 0.01-0.80] (p = 0.03). There were no significant differences in acute or chronic toxicities between groups. Conclusions Patients receiving postoperative RT alone for LA-cHNSCC had better OS than patients receiving concurrent systemic therapy. There were no differences in any other endpoints evaluated.

  14. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Kai [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of Life Science and Technology, Jinan University, Guangzhou (China); Chen, Maoyun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Xiang, Yangfei; Ma, Kaiqi [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Jin, Fujun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Wang, Xiao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Wang, Xiaoyan; Wang, Shaoxiang [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Wang, Yifei, E-mail: twang-yf@163.com [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China)

    2014-04-18

    Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

  15. The Impact of Adjuvant Therapy on Survival and Recurrence Patterns in Women With Early-Stage Uterine Carcinosarcoma: A Multi-institutional Study.

    Science.gov (United States)

    Guttmann, David M; Li, Hualei; Sevak, Parag; Grover, Surbhi; Jacobson, Geraldine; Feldman, Aharon; Rubin, Stephen; Chu, Christina; Bhatia, Sudershan; Elshaikh, Mohamed A; Lin, Lilie L

    2016-01-01

    The aim of the study was to characterize the impact of adjuvant therapy on survival in women with stage I/II uterine carcinosarcoma after primary surgery. We reviewed records of 118 consecutively treated women with 2009 International Federation of Gynecology and Obstetrics stage I/II uterine carcinosarcoma who underwent hysterectomy between 1990 and 2014 at 4 academic institutions. Patients were categorized by adjuvant treatment group into observation, chemotherapy only, radiation only, and combined chemotherapy and radiation. Survival analyses were conducted using Kaplan-Meier and Cox proportional hazards models. Median follow-up was 28 months (range, 1-244 months). Lymphadenectomy was performed in 94 patients (80%). Postoperative management included observation (n = 37 [31%]), chemotherapy alone (n = 19 [16%]), radiation therapy (RT) alone (n = 24 [20%]), and combined RT and chemotherapy (n = 38 [32%]). Radiation therapy modality included vaginal brachytherapy in 22 patients, pelvic external beam RT in 21 patients, and combination in 19 patients. In 58% of women, chemotherapy consisted of carboplatin/paclitaxel. Median overall survival for all women was 97 months. On univariate analysis, adjuvant treatment group was associated with improved overall survival (hazard ratio [HR], 0.74; confidence interval [CI], 0.58-0.96; p = 0.02), freedom from vaginal recurrence (HR, 0.55; CI, 0.37-0.82]; p = 0.004), and freedom from any recurrence (HR, 0.70; CI, 0.54-0.92; p = 0.01). Pairwise comparisons demonstrated a significant benefit to chemoradiation over other adjuvant treatments. Adjuvant treatment group remained a significant covariate for all 3 end points on multivariate analysis as well. In addition, lymphadenectomy improved overall survival on multivariate analysis (HR, 0.24; CI, 0.09-0.61; p = 0.003). Of patients under observation only who had a recurrence, 8 (44%) of 18 had a recurrence in the vagina as the sole site of recurrence. By contrast, of women who received

  16. Evaluation of Dhatri Avaleha as adjuvant therapy in Thalassemia (Anukta Vyadhi in Ayurveda).

    Science.gov (United States)

    Singh, Ruchi; Patel, K S; Anand, I P

    2010-01-01

    Thalassemia is the commonest single gene disorder in India. About 10,000 infants with Thalassemia major are born every year. The present study was under taken with a hope to prevail better quality of life to the Thalassemic patients. Pallor being the chief complaint, a randomized controlled trial was undertaken with Dhatri Avaleha as it is specially mentioned for Pandu, Kamala & Haleemaka Roga. Children between age group of 1 to 15 years were randomly divided in two groups: Drug treated group (Group A) and Control group (Group B). Assessment was done on subjective and objective parameters after 30 and 60 days of treatment with follow up of two month. Statistically significant (Ptransfusion interval in group 'A' in comparison to group 'B'. Dhatri Avaleha may have a potential to increase blood transfusion interval and decrease secondary infection and thus it can be used as supportive therapy with modern medical management.

  17. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy.

    Science.gov (United States)

    Woolf, Eric C; Syed, Nelofer; Scheck, Adrienne C

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo . In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  18. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy

    Science.gov (United States)

    Woolf, Eric C.; Syed, Nelofer; Scheck, Adrienne C.

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma. PMID:27899882

  19. Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

    Directory of Open Access Journals (Sweden)

    Eric C. Woolf

    2016-11-01

    Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  20. The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

    Science.gov (United States)

    Berlière, M; Roelants, F; Watremez, C; Docquier, M A; Piette, N; Lamerant, S; Megevand, V; Van Maanen, A; Piette, P; Gerday, A; Duhoux, F P

    2018-02-01

    In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically

  1. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial

    DEFF Research Database (Denmark)

    Rabaglio, M; Sun, Z; Price, K N

    2009-01-01

    BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 yea...

  2. Utilization pattern and survival outcomes of adjuvant therapies in high-grade nonretroperitoneal abdominal soft tissue sarcoma: A population-based study.

    Science.gov (United States)

    Green, William Ross; Chokshi, Ravi; Jabbour, Salma K; DeLaney, Thomas F; Mahmoud, Omar

    2018-02-01

    Nonretroperitoneal abdominal soft tissue sarcoma (NRA-STS) is a rare disease with limited data supporting its management. Our study aimed to reveal the utilization patterns of adjuvant therapy and its potential survival benefits using the National Cancer Data Base. The analysis included patients with resected high-grade NRA-STS. Chi-square analysis was used to evaluate distribution of patient and tumor-related factors within treatment groups. The Kaplan-Meier and Cox proportional hazards model were utilized to evaluate overall survival according to treatment approach. Multivariate analysis was used to determine the impact of these factors on patients' outcome. Matched propensity score analysis was implemented to control for imbalance of confounding variables. At median follow-up of 49 months, 5-year overall survival improved from 46% without adjuvant radiation therapy to 52% (P = 0.009) with radiotherapy delivery with a 30% reduction in hazard of death (95% confidence interval = 0.58-0.84). On multivariate analysis, age <50, tumor <8 cm, negative margins and radiotherapy delivery were significant predictors of improved survival. Chemotherapy was not associated with significant survival improvement (Hazard Ratios [HR]: 0.89, P = 0.28). Adjuvant radiotherapy was associated with improved survival in high-grade NRA-STS. Chemotherapy was not associated with a survival improvement; however, further studies are needed to refine treatment strategies. © 2017 John Wiley & Sons Australia, Ltd.

  3. Impact of adjuvant chemotherapy on cosmesis and complications in Stages I and II carcinoma of the breast treated by biopsy and radiation therapy

    International Nuclear Information System (INIS)

    Ray, G.R.; Fish, V.J.; Marmor, J.B.; Rogoway, W.; Kushlan, P.; Arnold, C.; Lee, R.H.; Marzoni, F.

    1984-01-01

    Cosmesis and complication rates were examined in patients with early stage carcinoma of the breast treated by biopsy and radiation therapy with and without adjuvant chemotherapy in an attempt to determine the effect of chemotherapy upon these parameters. Between April 1, l975 and June 1, 1980, 51 patients were treated with radiation therapy and adjuvant chemotherapy (XRT + ACT) and 83 patients with radiotherapy alone (XRT). Cosmetic results deteriorated with time in both groups but to a greater extent in the XRT + ACT group. Comparison of the two treatment groups revealed that complication rates were significantly incresed in the XRT + ACT group. Of the 51 patients in the XRT + ACT group, 21 patients (41%) suffered complications compared to 8 (10%) of the 83 patients in the XRT group. This difference in complication rates resulted primarily from an increased incidence in the XRT + ACT group of wet desquamation in the electron beam portal used to treat the internal mammary lymph nodes and a trend towards a higher incidence of spontaneous nonpathologic rib fractures, myositis and arm edema. The authors' preliminary conclusions are that adjuvant chemotherapy has a negative impact upon cosmesis and complications rates in patients being treated with definitive radiotherapy. However, cosmetic results remain satisfactory and complication rates are maintained at an acceptable level

  4. Adjuvant radiation therapy in locally advanced non-small cell lung cancer: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based clinical practice guideline.

    Science.gov (United States)

    Rodrigues, George; Choy, Hak; Bradley, Jeffrey; Rosenzweig, Kenneth E; Bogart, Jeffrey; Curran, Walter J; Gore, Elizabeth; Langer, Corey; Louie, Alexander V; Lutz, Stephen; Machtay, Mitchell; Puri, Varun; Werner-Wasik, Maria; Videtic, Gregory M M

    2015-01-01

    To provide guidance to physicians and patients with regard to the use of adjuvant external beam radiation therapy (RT) in locally advanced non-small cell lung cancer (LA NSCLC) based on available medical evidence complemented by consensus-based expert opinion. A panel authorized by the American Society for Radiation Oncology (ASTRO) Board of Directors and Guidelines Subcommittee conducted 2 systematic reviews on the following topics: (1) indications for postoperative adjuvant RT and (2) indications for preoperative neoadjuvant RT. Practice guideline recommendations were approved using an a priori-defined consensus-building methodology supported by ASTRO and approved tools for the grading of evidence quality and the strength of guideline recommendations. For patients who have undergone surgical resection, high-level evidence suggests that use of postoperative RT does not influence survival, but optimizes local control for patients with N2 involvement, and its use in the setting of positive margins or gross primary/nodal residual disease is recommended. No high-level evidence exists for the routine use of preoperative induction chemoradiation therapy; however, modern surgical series and a post-hoc Intergroup 0139 clinical trial analysis suggest that a survival benefit may exist if patients are properly selected and surgical techniques/postoperative care is optimized. A consensus and evidence-based clinical practice guideline for the adjuvant radiotherapeutic management of LA NSCLC has been created addressing 2 important questions. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Ginkgo biloba: An adjuvant therapy for progressive normal and high tension glaucoma

    Science.gov (United States)

    Cybulska-Heinrich, A.K.; Mozaffarieh, M.

    2012-01-01

    Gingko biloba has been used for hundreds of years to treat various disorders such as asthma, vertigo, fatigue and, tinnitus or circulatory problems. Two of the main extracts are EGb761 and LI 1370. Most pharmacological, toxicological and clinical studies have focused on the neuroprotective value of these two main extracts. Neuroprotection is a rapidly expanding area of research. This area is of particular interest due to the fact that it represents a new avenue of therapy for a frustrating disease that may progress despite optimal treatment. One such disease is glaucoma. Glaucoma leads to the loss of retinal ganglion cells and their axons but also to tissue remodelling which involves both the optic nerve head and the retina. In the retina the astrocytes get activated. In addition, the optic nerve gets thinner and the cells of the lateral geniculate ganglion disappear partially. On average, ocular blood flow (OBF) is reduced in glaucoma patients in various tissues of the eye. Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage. Nevertheless, there is little doubt that other risk factors besides IOP are involved. One such risk factor is a primary vascular dysregulation (PVD) occurring in patients with a disturbed autoregulation, another risk factor is oxidative stress. PMID:22355250

  6. Adjuvant use of acoustic pressure wound therapy for treatment of chronic wounds: a retrospective analysis.

    Science.gov (United States)

    Cole, Pamela S; Quisberg, Jennifer; Melin, M Mark

    2009-01-01

    Small studies have indicated that the addition of acoustic pressure wound therapy (APWT) to conventional wound care may hasten healing of chronic wounds. We evaluated our early clinical experience using APWT as an adjunct to conventional wound care. The study was a retrospective chart review of consecutive patients receiving APWT in addition to conventional wound care in a hospital-based, primarily outpatient setting. Medical records of all patients treated with APWT between August 2006 and October 2007 were reviewed. Analysis included the 41 patients with 52 wounds who received APWT at least 2 times per week during the study period. Statistical comparisons were made for wound dimensions, tissue characteristics, and pain at start versus end of APWT. Thirty-eight percent of wounds (N = 20) healed completely with a mean 6.8 weeks of APWT. Median wound area and volume decreased significantly (88% [P wounds with greater than 75% granulation tissue increased from 26% (n = 12) to 80% (n = 41) (P wounds (P = .006). This early experience supplementing conventional wound care with APWT suggests it may promote healing in chronic wounds, where the ordered cellular and molecular processes leading to healing have stalled.

  7. Family-building After Breast Cancer: Considering the Effect on Adherence to Adjuvant Endocrine Therapy.

    Science.gov (United States)

    Benedict, Catherine; Thom, Bridgette; Teplinsky, Eleonora; Carleton, Jane; Kelvin, Joanne F

    2017-06-01

    Adherence to endocrine therapy (ET) is a longstanding problem in breast cancer (BC) survivorship care, particularly among younger women. Younger patients have reported lower ET initiation rates and greater rates of early discontinuation and are considered an "at risk" group for nonadherence. For women who hope to have children in the future, concerns about premature menopause and the implications of postponing childbearing for the 5 to 10 years of ET are widespread. Preliminary evidence suggests that prioritizing fertility, along with concerns about side effects, leads to ET noninitiation and early discontinuation. Clinical efforts to improve adherence might need to consider patients' family-building goals during the course of treatment and to appropriately counsel patients according to their priorities and family-building intentions. Educational materials about family building after cancer are still not consistently available or provided. Helping patients to access trusted informational resources and decision support tools, in conjunction with medical counseling, will promote informed decisions regarding ET adherence and pregnancy that are medically appropriate. Such shared patient-provider decision-making about ET adherence and pregnancy could help to maximize patient autonomy by incorporating their values, preferences, and priorities into decisions, using providers' medical expertise. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    William Eardley

    2010-04-01

    Full Text Available William Eardley, Cory TothDepartment of Clinical Neurosciences and the University of Calgary, Calgary, AB, CanadaAbstract: Although many therapies are used in the management of neuropathic pain (NeP due to polyneuropathy (PN, few comparison studies exist. We performed a prospective, non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain Inventory [BPI], quality of life and health status measures [EuroQol 5 Domains, EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and Depression Scale [HADS] and Short Form 36 Health Survey [SF-36] after 6 months of therapy. Significant improvements in VAS pain scores occurred for all treatment groups after 6 months. Improvements in aspects of daily life and anxiety were identified in all treatment groups. Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management. We advocate for head-to-head, randomized, double-blinded studies of current NeP therapies.Keywords: peripheral neuropathy, neuropathic pain, pharmacotherapy, venlafaxine, gabapentin

  9. Changes in Lymphangiogenesis and Vascular Endothelial Growth Factor Expression by Neo-Adjuvant Hormonal Therapy in Prostate Cancer Patients.

    Science.gov (United States)

    Asai, Akihiro; Miyata, Yasuyoshi; Matsuo, Tomohiro; Shida, Yohei; Hakariya, Tomoaki; Ohba, Kojiro; Sakai, Hideki

    2017-02-01

    The anti-cancer mechanism of neo-adjuvant hormonal therapy (NHT) is not well understood. Lymphangiogenesis plays an important role in cancer progression and is regulated by a complex mechanism that includes vascular endothelial growth factor (VEGF) signaling. However, there is little information regarding relationship between lymphangiogenesis and androgen deprivation. The aim of this study was to clarify changes in lymphangiogenesis and VEGF expression induced by androgen deprivation in prostate cancer in vivo and in vitro. Patients who had undergone a radical prostatectomy were enrolled in the study (NHT, n = 60 and non-NHT, n = 64). Lymph vessels were identified by D2-40 immunoreactivity and lymph vessel density and lymph vessel area (LVD and LVA, respectively) were measured from micrographs. The expression of VEGF-A, -B, -C, and -D was evaluated by immunohistochemistry. The prognostic value of LVD and LVA for biochemical recurrence was also investigated. Mean LVD ± SD was higher in the NHT than in the non-NHT group (11.3 ± 3.0 vs. 7.1 ± 3.4 per high power field; P cancer cell line. LVA was found to be an independent predictor of biochemical recurrence in patients who received NHT. Our results demonstrate that NHT stimulates lymphangiogenesis via upregulation of VEGF-C and -D, which may increase LVA and affect the outcome of prostate cancer patients. This findings were supported by in vitro data of prostate cancer cell. Prostate 77:255-262, 2017. © 2016 The Authors. The Prostate Published by Wiley Periodicals, Inc. © 2016 The Authors. The Prostate Published by Wiley Periodicals, Inc.

  10. External Validation and Optimization of International Consensus Clinical Target Volumes for Adjuvant Radiation Therapy in Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Abhinav V. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Christodouleas, John P. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Wu, Tianming [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Smith, Norman D.; Steinberg, Gary D. [Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States)

    2017-03-15

    Purpose: International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. Methods and Materials: Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. Results: Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). Conclusions: Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.

  11. Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus

    Directory of Open Access Journals (Sweden)

    Pradnya J Londhe

    2014-01-01

    Full Text Available Background: Rituximab, a monoclonal anti-CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23 and pemphigus foliaceus (n = 1 treated with rituximab in addition to steroids and immunosuppressants. Aims: To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. Methods: We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid-dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m 2 of body-surface area. One similar infusion was repeated after 3 months of 3 rd dose. We observed the clinical outcome after 6 months of 3 rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission. Observations: After follow-up of 7-24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. Conclusion: Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

  12. The Effectiveness of Adjuvant Hyperbaric Oxygen Therapy in Adults who Underwent Hypospadias Surgery

    Directory of Open Access Journals (Sweden)

    Onder Kara

    2017-01-01

    Full Text Available Aim: To evaluate the role of hyperbaric oxygen therapy (HBO2T with buccal mucosal tube urethroplasty in adult patients with hypospadias. Material and Method: Sixteen adult patients with hypospadias were included in our study. Patients with a short urethra and penile curvature were treated in two stages (orthoplasty buccal mucosal tube urethroplasty. Buccal mucosa was taken and prepared for tube urethroplasty around a 16 French (Fr nelaton catheter and the urethral tube was introduced between the urethral meatus and glans penis. Beginning the 1st postoperative day (HBO2T was applied for 10 sessions during weekdays in 13 patients. Results: The mean age was 21 (±1.23 years and mean follow-up time was 10.1 (±2.1 months. In the group who received HBO2T postoperatively (n=13, a two-stage (orthoplasty buccal mucosal tube urethroplasty procedure was performed in 6 (46%, and the mean length of graft was 5.4 (±1.23 cm. In this group of 13 the success rate without any additional manipulations (urethrotomy intern, fistula repair was 54% (7/13. After additional manipulations, complete healing was achieved in 11 out of 13 patients (84.6%. In the group who did not receive HBO2T postoperatively (n=3, a two-stage procedure was performed in 1 patient (33%, and the mean length of graft was 8 (±5 cm. In this group of 3, complete healing was not achieved in any of these patients as a result of the hypospadias surgery. However, after the additional manipulations, complete healing was achieved in 1 patient (33%. Discussion: Given the promising rates of surgical success, postoperative HBO2T might be considered as a supportive treatment modality for adult patients with hypospadias who undergo buccal mucosal tube urethroplasty. Randomized controlled studies are needed.

  13. Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

    Science.gov (United States)

    Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

    2016-02-01

    This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A. © The Author(s) 2015.

  14. Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

    Directory of Open Access Journals (Sweden)

    M.V. Borgo

    2011-08-01

    Full Text Available Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR. Female SHR were divided into four groups (N = 7 each: sham-operated (SHAM, sham-operated and treated with tamoxifen (10 mg/kg by gavage for 90 days (TAMOX, ovariectomized (OVX, and ovariectomized and treated with tamoxifen (OVX+TAMOX. Mean arterial pressure (MAP, heart rate (HR, coronary perfusion pressure (CPP, and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67%, respectively in the OVX+TAMOX group compared to the OVX group (P < 0.01. The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg when compared to the OVX group (P < 0.01 and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05. Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01. Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

  15. Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

    2014-03-01

    Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-07-01

    Full Text Available ≥Ying Zhang,1 Trong Kim Le,1 James W Shaw,2 Srividya Kotapati31Center for Observational Research and Data Sciences, Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Hopewell, NJ, USA; 2Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Princeton, NJ, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Wallingford Center, CT, USABackground: This study examines real-world drug utilization patterns, health care resource use, and costs among patients receiving adjuvant treatment with IFN versus patients receiving no treatment ("observation" for malignant melanoma following surgery.Methods: A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan® to identify all adjuvant melanoma patients (aged ≥18 years diagnosed between June 2007 and June 2011 who had a lymph node dissection (ie, index surgery and were treated with IFN or subsequently observed. Health care resource use and costs of services were converted to 2012 US dollars and were evaluated and compared using multivariable regression.Results: Of 1,999 eligible subjects with melanoma surgery claims, 179 (9.0% were treated with IFN and 1,820 (91.0% were observed. The median duration (days and number of doses of IFN therapy were 73 and 36, respectively. Among IFN-treated patients, only 10.6% completed ≥80% of maintenance therapy. The total average cost for patients treated with IFN was US$60,755±$3,972 (n=179; significantly higher than for patients undergoing observation ($31,641±$2,471; P<0.0001. Similar trends were observed when evaluating total cost components, including melanoma-related and non-melanoma–related medical costs. Among the melanoma-related medical costs, outpatient services, including office visits and laboratory testing, represented between 33% and 53% of total costs and

  17. Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

    Science.gov (United States)

    Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

    2017-08-01

    To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p hemoglobin (Hb) level >12 g/dl was a factor with an average association with the overall survival (p 12 g/dl tended to affect the overall survival in the definitive radiation group patients.

  18. Antimicrobial photodynamic therapy adjuvant to non-surgical periodontal therapy in patients with diabetes mellitus: A meta-analysis.

    Science.gov (United States)

    Abduljabbar, Tariq; Vohra, Fahim; Javed, Fawad; Akram, Zohaib

    2017-03-01

    To determine whether treatment with antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) improves periodontal clinical and glycemic outcomes in chronic periodontitis patients (CP) with type 2 diabetes mellitus (DM). Databases (MEDLINE via PubMed; EMBASE; Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) were searched up to and including October 2016. The addressed PICO question was: "What are the effects of aPDT as an adjunct to SRP in terms of periodontal and glycemic outcomes as compared to SRP alone in individuals with DM?" Four randomized clinical trials were included in the present review. All studies reporting clinical periodontal and metabolic parameters, showed that aPDT was effective in the treatment of CP in DM subjects at follow up. Considering the effects of aPDT as an adjunct as compared to SRP alone on clinical signs of CP in DM subjects, no difference could be observed for all evaluated parameters (PD: Z=-0.61, P=0.54; CAL: Z=0.27, P=0.78; HbA1c: Z=0.138, P=0.89) CONCLUSION: It remains debatable whether aPDT is effective as an adjunct to SRP than SRP alone in patients having CP with DM, given that the scientific evidence is weak. In terms of periodontal parameters and glycemic levels, aPDT does not provide additional benefit in the treatment of CP in DM patients. However, further randomized clinical trials with standard laser parameters and long follow up periods are warranted to study periodontal and glycemic outcomes in this regard. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen.

    Science.gov (United States)

    Mendes-Pereira, Ana M; Sims, David; Dexter, Tim; Fenwick, Kerry; Assiotis, Ioannis; Kozarewa, Iwanka; Mitsopoulos, Costas; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J; Ashworth, Alan

    2012-02-21

    Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance to tamoxifen remains a major clinical problem. Here we have used a genome-wide functional profiling approach to identify multiple genes that confer resistance or sensitivity to tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, we have profiled the impact of more than 56,670 RNA interference reagents targeting 16,487 genes on the cellular response to tamoxifen. This screen, along with subsequent validation experiments, identifies a compendium of genes whose silencing causes tamoxifen resistance (including BAP1, CLPP, GPRC5D, NAE1, NF1, NIPBL, NSD1, RAD21, RARG, SMC3, and UBA3) and also a set of genes whose silencing causes sensitivity to this endocrine agent (C10orf72, C15orf55/NUT, EDF1, ING5, KRAS, NOC3L, PPP1R15B, RRAS2, TMPRSS2, and TPM4). Multiple individual genes, including NF1, a regulator of RAS signaling, also correlate with clinical outcome after tamoxifen treatment.

  20. The Effect of Mindfulness-Based Music Therapy on Attention and Mood in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Study.

    Science.gov (United States)

    Lesiuk, Teresa

    2015-05-01

    To explore the efficacy of mindfulness-
based music therapy (MBMT) to improve attention and decrease mood distress experienced by women with breast cancer receiving adjuvant chemotherapy. Quantitative, descriptive, longitudinal approach. A comprehensive cancer hospital and a university in southern Florida. 15 women with a diagnosis of breast cancer, stages I-III, receiving adjuvant chemotherapy. Participants individually received MBMT for one hour per week for four weeks. The sessions consisted of varied music activities accompanied by mindfulness attitudes, or mental strategies that enhance moment-to-moment awareness, and weekly homework. Demographic information was collected at baseline. Attention was measured using Conners' Continuous Performance Test II. Mood was measured using the Profile of Mood States-Brief Form. Narrative comments collected from the homework assignments served to reinforce quantitative data. Repeated measures analysis of variance showed that attention improved significantly over time. Although all mood states significantly improved from the beginning to the end of each MBMT session, the mood state of fatigue decreased significantly more than the other mood states. MBMT enhances attention and mood, particularly the mood state of fatigue, in women with breast cancer receiving adjuvant chemotherapy. 
. A preferred music listening and mindfulness exercise may be offered to women with breast cancer who experience attention problems and mood distress.

  1. [CYP2D6 polymorphisms and tamoxifen: therapeutic perspectives in the management of hormonodependent breast cancer patients].

    Science.gov (United States)

    Barrière, J; Formento, J-L; Milano, G; Ferrero, J-M

    2010-03-01

    Tamoxifen is a prodrug mainly metabolized by the CY2D6 cytochrome. More than 80 variants of the CYP2D6 gene have been identified. They predict four different enzymatic phenotypes: ultra-rapid metabolizers (UM), extensive metabolizers (EM), intermediate metabolizers (IM) and poor metabolizers (PM). Six retrospectives studies suggest a link between some polymorphisms of the CYP2D6 and tamoxifen efficacy and two studies have found no statistically significant data. Today, level of proof remains insufficient to recommend the testing of a patient's genotype before tamoxifen prescription. Designing prospective studies is necessary before considering therapy strategies based on pharmacogenetics data. In pre-menopausal breast cancer PM or IM patients, an increase in dosage of tamoxifen or a treatment with LH-RH analogues with aromatase inhibitors (AI) may be beneficial instead of the actual recommendations of a 5-year tamoxifen therapy. In postmenopausal EM patients, tamoxifen may be as efficient as AI. In post-menopausal PM patients, a switch strategy may be inferior to a 5-year IA strategy, which would therefore be the standard of care.

  2. Efficacy of Curcumin as Adjuvant Therapy to Induce or Maintain Remission in Ulcerative Colitis Patients: an Evidence-based Clinical Review

    Directory of Open Access Journals (Sweden)

    Marcellus Simadibrata

    2018-01-01

    Full Text Available Background: treatment guidelines for ulcerative colitis (UC not yet established. Currently, mesalazine, corticosteroids, and immunomodulators are treatment options for UC. However, they are known to have unpleaseant side effects such as nausea, vomiting, headaches, hepatitis, and male infertility. Curcumin is found in Turmeric plants (Curcuma longa L., which possesses both anti-inflammatory and antioxidant properties. This study aimed to determine whether curcumin as adjuvant therapy can induce or maintain remission in UC patients. Methods: structured search in three database (Cochrane, PubMed, Proquest using “Curcumin”, “remission” and “Ulcerative Colitis” as keywords. Inclusion criteria is randomized controlled trials (RCTs, meta-analysis, or systematic review using curcumin as adjuvant therapy in adult UC patients. Results: we found 49 articles. After exclusion, three RCTs were reviewed; two examined curcumin efficacy to induce remission and one for remision maintenance in UC. Curcumin was significantly more effective than placebo in all RCTs. The efficacy of curcumin could be explained by its anti-inflammatory properties, which inhibit NF-kB pathway. Regulation of oxidant/anti-oxidant balance can modify the release of cytokines. However, methods varied between RCTs. Therefore, they cannot be compared objectively. Futhermore, the sample size were small (n= 50, 45, 89 therefore the statistical power was not enough to generate representative results in all UC patients. Conclusion: Available evidence showed that curcumin has the potential to induce and maintain remission in UC patients with no serious side effects. However, further studies with larger sample size are needed to recommend it as adjuvant therapy of ulcerative colitis.

  3. Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

    Energy Technology Data Exchange (ETDEWEB)

    Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no [Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Engellau, Jacob [Department of Oncology, Skåne University Hospital, Lund (Sweden); Engström, Katarina [Department of Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden); Bauer, Henrik C. [Department of Molecular Medicine and Surgery, Section for Orthopaedics and Sports Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm (Sweden); Monge, Odd R. [Department of Oncology, Haukeland University Hospital, Bergen (Norway); Muren, Ludvig P. [Department of Physics and Technology, University of Bergen, Bergen (Norway); Department of Medical Physics, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Eide, Geir E. [Centre for Clinical Research, Haukeland University Hospital, Bergen (Norway); Department of Public Health and Primary Health Care, University of Bergen, Bergen (Norway); Trovik, Clement S. [Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Bruland, Øyvind S. [Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway)

    2013-08-01

    Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.

  4. Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients.

    Science.gov (United States)

    Perez, Cédric; Huttner, Angela; Assal, Mathieu; Bernard, Louis; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

    2010-05-01

    No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (7 days). Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with 14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

  5. EFFECTS OF BETAHISTINE DIHYDROCHLORIDE AS ADJUVANT TO ENALAPRIL THERAPY OF PATIENTS WITH CHRONIC HEART FAILURE CLASS II-II (NYHA SUFFERING FROM GIDDINESS

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2008-01-01

    Full Text Available Aim. To study adjuvant effect of betahistine dihydrochloride to ACE inhibitors in patients with chronic heart failure (CHF class II-III suffering from giddiness.Material and methods. 61 patients with CHF class II-III, ejection fraction ≤45% (Simpson suffering from giddiness were involved into randomized open parallel study. Patients were randomized to Betahistine dihydrochloride plus basic CHF therapy or only basic therapy groups. Enalapril dose titration was performed in all patients. Quality of life and giddiness severity evaluation, electrocardiogram was performed initially and after treatment. Clinical examination results, drug therapy and adverse event were registered at each visit.Results. The target ACE inhibitor dose (≥20 mg daily was reached in 97 % of patients. It led to significant reduction of dyspnea, edemas, CHF class reduction and life quality increase. Significant differences between investigated groups were not found. Reduction of giddiness severity was shown in both groups. There was a trend to more prominent improvement of life quality (р=0,08 and more frequent achievement of target ACE inhibitor dose in patients treated with betahistine dihydrochloride.Conclusion. The target ACE inhibitor dose can be achieved more than in 90% of patients with CHF class II-III without hypotension symptoms. Adjuvant usage of betahistine dihydrochloride is necessary in patients with CHF still suffering from giddiness after achievement of target ACE inhibitor dose.

  6. Camel milk as an adjuvant therapy for the treatment of type 1 diabetes: verification of a traditional ethnomedical practice.

    Science.gov (United States)

    Mohamad, Ragaa Hosny; Zekry, Zekry Khalid; Al-Mehdar, Hussain A; Salama, Omar; El-Shaieb, Siad Ebrahim; El-Basmy, Amany A; Al-said, Mohamad Gamil Abdel Monem; Sharawy, Sabry Mohamed

    2009-04-01

    There is a traditional belief in the Middle East that regular consumption of camel milk may aid in prevention and control of diabetes. The aim of this work was to evaluate the efficacy of camel milk as an adjuvant therapy in young type 1 diabetics. This 16-week randomized study enrolled 54 type 1 diabetic patients (average age 20 years) selected from those attending the outpatient diabetes clinic of the Menofia University Hospital, affiliated with Egypt's National Cancer Institute. Subjects were randomly divided into two groups of 27 patients: one received usual management (diet, exercise, and insulin), whereas the other received 500 mL of camel milk daily in addition to standard management. A control group of 10 healthy subjects was also assessed. The following parameters were evaluated at baseline and at 4 and 16 weeks: hemoglobin A1c (HbA1c), human C-peptide, lipid profile, serum insulin, anti-insulin antibodies, creatinine clearance, albumin in 24-hour urine, body mass index, and Diabetes Quality of Life score. The following parameters were significantly different between the usual-management group versus the camel milk group after 16 weeks: fasting blood sugar (227.2 +/- 17.7 vs. 98.9 +/- 16.2 mg/dL), HbA1c (9.59 +/- 2.05[%] vs. 7.16 +/- 1.84[%]), serum anti-insulin antibodies (26.20 +/- 7.69 vs. 20.92 +/- 5.45 microU/mL), urinary albumin excretion (25.17 +/- 5.43 vs. 14.54 +/- 5.62 mg/dL/24 hours), daily insulin dose (48.1 +/- 6.95 vs. 23 +/- 4.05 units), and body mass index (18.43 +/- 3.59 vs. 24.3 +/- 2.95 kg/m(2)). Most notably, C-peptide levels were markedly higher in the camel milk group (0.28 +/- 0.6 vs. 2.30 +/- 0.51 pmol/mL). These results suggest that, as an adjunct to standard management, daily ingestion of camel milk can aid metabolic control in young type 1 diabetics, at least in part by boosting endogenous insulin secretion.

  7. Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up of a randomized clinical trial.

    Science.gov (United States)

    Rutqvist, L E; Pettersson, D; Johansson, H

    1993-02-01

    This paper presents long-term results from a randomized trial of pre- or postoperative megavoltage radiation therapy versus surgery alone in pre- and postmenopausal women with operable breast cancer. Treatment outcome after relapse among patients who developed loco-regional recurrences was also analyzed. A total of 960 patients were included in the trial. The mean follow-up was 16 years (range: 13-19 years). The radiation therapy was individually planned. It included the chest wall (and the breast in the preoperative cases) and the regional lymph nodes. The tumor dose was 45 Gy/5 weeks. No adjuvant systemic therapy was used. The results showed a significant benefit with radiation therapy in terms of recurrence-free survival during the entire follow-up period. There was also an overall survival difference-corresponding to a 16% reduction of deaths-in favor of the irradiated patients which, however, was not statistically significant (p = 0.09). Among those 169 patients who developed locoregional recurrences long-term control was only achieved in about one-third of the cases. This figure was similar among those who had received adjuvant radiation therapy (34%) compared to those initially treated with surgery alone (32%). This implied that the overall proportion of patients who eventually developed uncontrolled local disease was significantly higher among those initially allocated to surgery alone (16%) compared to those allocated to pre- or postoperative radiation therapy (6%, p < 0.01). These results suggest that local undertreatment may be deleterious in subgroups of patients.

  8. Increased Lipiodol uptake in hepatocellular carcinoma possibly due to increased membrane fluidity by dexamethasone and tamoxifen

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Stephanie, E-mail: stephanie.becker@rouen.fnclcc.f [Department of Nuclear Medicine, Centre E. Marquis, F-35042 Rennes (France); INSERM U 991, Rennes, F-35033 France (France); European University of Brittany, F-35000 Rennes (France); Department of Nuclear Medicine, Centre H. Becquerel, F-76038 Rouen (France); Ardisson, Valerie; Lepareur, Nicolas [Department of Nuclear Medicine, Centre E. Marquis, F-35042 Rennes (France); INSERM U 991, Rennes, F-35033 France (France); European University of Brittany, F-35000 Rennes (France); Sergent, Odile [European University of Brittany, F-35000 Rennes (France); UPRES EA SeRAIC, IFR 140, University of Rennes 1, F-35043 Rennes (France); Bayat, Sahar [INSERM U936 Department of Biostatistics, CHRU Pontchaillou, F-35033 Rennes (France); Noiret, Nicolas [European University of Brittany, F-35000 Rennes (France); Ecole Nationale Superieure de Chimie de Rennes, UMR CNRS 6226, F-35708 Rennes (France); Gaboriau, Francois; Clement, Bruno [INSERM U 991, Rennes, F-35033 France (France); Boucher, Evelyne [INSERM U 991, Rennes, F-35033 France (France); Department of Medical Oncology, Centre E. Marquis, F-35042 Rennes (France); Raoul, Jean-Luc [INSERM U 991, Rennes, F-35033 France (France); European University of Brittany, F-35000 Rennes (France); Department of Medical Oncology, Centre E. Marquis, F-35042 Rennes (France); Garin, Etienne [Department of Nuclear Medicine, Centre E. Marquis, F-35042 Rennes (France); INSERM U 991, Rennes, F-35033 France (France); European University of Brittany, F-35000 Rennes (France)

    2010-10-15

    Introduction: Lipiodol is used as a vector for chemoembolization or internal radiotherapy in unresectable hepatocellular carcinomas (HCCs). The aim of this study is to improve the tumoral uptake of Lipiodol by modulating membrane fluidizing agents to optimize the effectiveness of Lipiodol vectorized therapy. Methods: The effect of dexamethasone and tamoxifen on membrane fluidity was studied in vitro by electron paramagnetic resonance applied to rat hepatocarcinoma cell line N1S1. The tumoral uptake of Lipiodol was studied in vivo on rats with HCC, which had been previously treated by dexamethasone and/or tamoxifen, after intra-arterial administration of {sup 99m}Tc-SSS-Lipiodol. Results: The two molecules studied here exhibit a fluidizing effect in vitro which appears dependent on time and dose, with a maximum fluidity obtained after 1 hr at concentrations of 20 {mu}M for dexamethasone and 200 nM for tamoxifen. In vivo, while the use of dexamethasone or tamoxifen alone tends to lead to increased tumoral uptake of Lipiodol, this effect does not reach levels of significance. On the other hand, there is a significant increase in the tumoral uptake of {sup 99m}Tc-SSS-Lipiodol in rats pretreated by both dexamethasone and tamoxifen, with a tumoral uptake (expressed in % of injected activity per g of tumor) of 13.57{+-}3.65% after treatment, as against 9.45{+-}4.44% without treatment (P<.05). Conclusions: Dexamethasone and tamoxifen fluidify the N1S1 cells membrane, leading to an increase in the tumoral uptake of Lipiodol. These drugs could be combined with chemo-Lipiodol-embolization or radiolabeled Lipiodol, with a view to improving the effectiveness of HCCs therapy.

  9. Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders : Results From a Randomized, Double-Blind, Placebo-Controlled Trial

    NARCIS (Netherlands)

    Laan, Wijnand; Grobbee, Diederick E.; Selten, Jean-Paul; Heijnen, Cobi J.; Kahn, Rene S.; Burger, Huibert

    Objective: Inflammatory processes may play a role in the pathophysiology of schizophrenia. The aim of this study was to determine the efficacy of adjuvant treatment with aspirin (acetylsalicylic acid) in schizophrenia spectrum disorders. Method: This randomized, double-blind, placebo-controlled

  10. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves ... a link to this page included, e.g., “Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves ...

  11. Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of tamoxifen, anastrozole, and letrozole in human plasma and its application to a clinical study.

    Science.gov (United States)

    Beer, Beate; Schubert, Birthe; Oberguggenberger, Anne; Meraner, Verena; Hubalek, Michael; Oberacher, Herbert

    2010-10-01

    There is substantial evidence that circulating estrogens promote the proliferation of breast cancer. Consequently, adjuvant hormonal treatment strategies targeting estrogen action have been established. Such hormonal therapies include selective estrogen receptor modulators, such as tamoxifen, which interfere at the estrogen receptors directly, or non-steroidal aromatase inhibitors, such as anastrozole and letrozole, which inhibit estrogen synthesis through blocking the aromatase, a key enzyme of estrogen production. Despite considerable therapeutic success, in several cases, the use of these drugs is limited by side effects that have been described to significantly impair the adherence of patients to endocrine treatment. However, objective data concerning patient adherence and its clinical relevance are limited. One promising approach to check patient-reported adherence is drug monitoring in human plasma. Therefore, a liquid chromatography-tandem mass spectrometry method to determine the plasma concentrations of tamoxifen, anastrozole, and letrozole has been developed and fully validated according to guidelines for clinical and forensic toxicology. The validation criteria evaluated were selectivity, linearity, accuracy and precision, limit of quantification, recovery and matrix effects, sample stability, and carryover. The six-point calibration curves showed linearity over the range of concentrations from 25 to 500 ng/ml for tamoxifen, 5 to 200 ng/ml for anastrozole, and 10 to 300 ng/ml for letrozole. The intra- and inter-day precision and accuracies were always better than 15%. The validated procedure was successfully applied to a clinical study (Patient-Reported Outcomes in Breast Cancer Patients undergoing Endocrine Therapy, PRO-BETh). A major aim of PRO-BETh study is the comprehensive evaluation of adherence to treatment in pre- and post-menopausal women with breast cancer. Plasma samples of 310 breast cancer patients undergoing anti-estrogen therapy were

  12. Sugarcane bagasse dietary fiber as an adjuvant therapy for stable chronic obstructive pulmonary disease: a four-center, randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Liu, Miao; Zheng, Fengjie; Ni, Lei; Sun, Yan; Wu, Ruohan; Zhang, Tianyu; Zhang, Jinchao; Zhong, Xianggen; Li, Yuhang

    2016-08-01

    To evaluate the efficacy and safety of sugarcane bagasse dietary fiber as an adjuvant therapy for improving quality of life in patients with stable chronic obstructive pulmonary disease (COPD). This was a multicenter, randomized, double-blind, placebo-controlled trial. A total of 196 participants were randomized into a trial group (treated with 6 g/day sugarcane bagasse plus conventional treatment, n = 98) and a control group (treated with placebo plus conventional treatment, n = 98). All efficacy analyses were performed according to the intention-to-treat (ITT) principle. A per-protocol analysis set (PPS) was used to analyze the cases that completed the clinical trial with good compliance. The trial period was 30 days, with a 6-month follow-up. Pre- and post-treatment pulmonary symptom scores (cough, sputum, wheezing, and dyspnea) were recorded for both groups. The St. George's Respiratory Questionnaire (SGRQ) and the modified Medical Research Council (mMRC) dyspnea scale were assessed before treatment and at the end of the 6-month follow- up. The ITT population was 178 and the PPS population was 166. Post-treatment pulmonary clinical symptoms and severity of dyspnea (mMRC and SGRQ evaluation) were significantly improved in both the trial group and the control group (ITT and PPS: P Sugarcane bagasse combined with conventional treatment improved quality of life in patients with stable COPD. Sugarcane bagasse appears to be a safe herbal medicine with potential for treating patients with stable COPD when taken orally as an adjuvant therapy.

  13. Radiation, chemotherapy or combined modality therapy in adjuvant treatment for stage III endometrial carcinoma in lower southern Thailand: disease recurrence and overall survival.

    Science.gov (United States)

    Pichatechaiyoot, Aroontorn; Buhachat, Rakchai; Boonyapipat, Sathana; Kanjanapradit, Kanet

    2014-03-01

    To survey disease-free survival (DFS) and overall survival (OS) of patients with stage III endometrial carcinoma treated with post-operative radiation and/or chemotherapy The medical records of patients with surgical stage III endometrial carcinoma, and receiving adjuvant treatment between January 2003 and December 2012 were reviewed DFS and OS were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Of the 54 eligible patients, 61% underwent radiation, 19% chemotherapy, and 20% chemotherapy with radiation. The median DFS was 36.7 months. The 3-year DFS and OS was 51.9% (95% CI 36.3-74.1%) and 70.6% (95% CI 57.4-86.8%), respectively. There was no significant difference in DFS and OS among treatment groups. Cox regression analysis showed grade 2-3 tumors and menopause were associated with poor DFS and OS. The DFS and OS in stage III endometrial carcinoma receiving postoperative adjuvant therapy were quite good and were not different among radiation therapy, chemotherapy, and combined treatment groups. The multi-center randomized prospective study was needed to determine the standard modality.

  14. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  15. Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Yasushi Hamaya

    Full Text Available Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST is a genetic signature found in up to 60% of colorectal cancers (CRCs that is caused by somatic dysfunction of the DNA mismatch repair (MMR protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer and hMutSβ (hMSH2-hMSH3 heterodimer MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci. Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44% EMAST cancers. Ninety-four patients (41% received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05. We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36. There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H.

  16. Effect of adjuvant recombinant EPO therapy on neural functional recovery, inflammation and erythrocyte glucose metabolism in patients with severe craniocerebral injury

    Directory of Open Access Journals (Sweden)

    Zeng Lu

    2017-02-01

    Full Text Available Objective: To study the effect of adjuvant recombinant EPO therapy on neural functional recovery, inflammation and erythrocyte glucose metabolism in patients with severe craniocerebral injury. Methods: A total of 78 patients with severe craniocerebral injury treated in our hospital between May 2013 and March 2016 were selected and randomly divided into the EPO group and control group who received recombinant human erythropoietin (rhEPO combined with conventional therapy and conventional therapy respectively. Before treatment as well as 7 d and 14 d after treatment, the degree of brain tissue hypoxia, nerve injury and inflammation as well as erythrocyte glucose metabolism were evaluated respectively. Results: PbtO2 levels, serum NGB and HGB content as well as PFK activity of both groups 7 d and 14 d after treatment were significantly higher than those before treatment while serum NF-H, NF-L, NF-M, NSE, S100β, IL-2, P-selectin and sICAM-1 content as well as G-6PD and AR activity were significantly lower than those before treatment; PbtO2 levels, serum NGB and HGB content as well as PFK activity of EPO group 7 d and 14 d after treatment were significantly higher than those of control group while serum NF-H, NF-L, NF-M, NSE, S100 β, IL-2, P-selectin and sICAM-1 content as well as G-6PD and AR activity were significantly lower than those of control group. Conclusion: Adjuvant recombinant EPO therapy can inhibit inflammation and improve erythrocyte glucose metabolism to reduce the nerve injury degree in patients with severe craniocerebral injury.

  17. Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-a light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides)

    International Nuclear Information System (INIS)

    Quiros, Peter A.; Jones, Glenn W.; Kacinski, Barry M.; Braverman, Irwin M.; Heald, Peter W.; Edelson, Richard L.; Wilson, Lynn D.

    1997-01-01

    Purpose: Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may benefit from adjuvant therapy after completing total skin electron beam therapy (TSEBT). We report the results for (T1(T2)) CTCL patients treated with adjuvant oral psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS), disease-free survival (DFS), salvage of recurrence, and toxicity. Methods and Materials: Between 1974 and 1993, TSEBT was administered to a total of 213 patients with CTCL. Records were reviewed retrospectively, and a total of 114 patients were identified as having T1 or T2 disease. Radiotherapy was provided via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks. Beginning in 1988, patients were offered adjuvant PUVA within 2 months of completing TSEBT. This was started at 0.5-2 J/m 2 , 1-2 treatments/week, with a taper over 3-6 months. Therapy then continued once per month. There were 39 T1 and 75 T2 patients. Six T1 (15%) and eight T2 (11%) patients were treated with adjuvant PUVA. A further 49% of the 114 patients received adjuvant systemic therapy, 3% received spot external beam, 4% received adjuvant ECP, 2% received topical nitrogen mustard, 22% received a combination of therapies exclusive of PUVA, and 9% received no adjuvant therapy. Patients were balanced in all subgroups based on pre-TSEBT therapy. The median age of the cohort was 58 (range 20-88), with a median follow-up time of 62 months (range 3-179). Results: Within 1 month after completing of TSEBT, 97% of T1, and 87% of T2 patients had achieved a complete remission. Stratified by adjuvant therapy, none of six T1 and one of eight T2 patients who received adjuvant PUVA failed within the first 3 years after completion of TSEBT. A total of 43% of the T1 and T2 patients receiving other or no adjuvant treatment failed within the same time course. The 5-year OS for the entire cohort was 85%. Those who received PUVA had a 5-year OS of 100% versus a 5-year OS for the non

  18. Mitotically active leiomyoma of the uterus in a postmenopausal breast cancer patient receiving tamoxifen.

    Science.gov (United States)

    Liu, I-Feng; Yen, Yu-Shan; Cheng, Ya-Min; Chou, Cheng-Yang

    2006-06-01

    Mitotically active leiomyoma of the uterus complicated with postmenopausal vaginal bleeding has never been reported in Taiwan. Here, we present a case of mitotically active leiomyoma of the uterus complicated with postmenopausal vaginal bleeding in a breast cancer patient who had been receiving tamoxifen for 2 years. A 56-year-old woman visited our clinic due to abnormal vaginal spotting for 3 months. This patient had been menopausal for about 6 years without hormone replacement therapy. She had been suffering from breast cancer, had undergone conservative breast surgery, and had been taking tamoxifen (20 mg/day) for 2 years. Pelvic ultrasound was performed and revealed an 8.9 x 7.7 cm uterine mass. After simple total hysterectomy, we found an enlarged uterus with a mass over the posterior wall. Final pathology demonstrated a mitotically active leiomyoma, adenomyosis of the uterus, and proliferation of the endometrium. Endometrial cancer is rarely noted in breast cancer patients taking tamoxifen. Further, none have reported mitotically active leiomyoma of the uterus. From this case, endometrial proliferation and mitotically active leiomyoma of the uterus may be related to tamoxifen therapy, and should not be neglected in breast cancer patients.

  19. The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients.

    Science.gov (United States)

    Eggermont, Alexander M M; Dummer, Reinhard

    2017-11-01

    The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node-positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Locoregional failure of postmastectomy patients with 1-3 positive axillary lymph nodes without adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Cheng, Jason C.-H.; Chen, C.-M.; Liu, M.-C.; Tsou, M.-H.; Yang, P.-S.; Jian, J. J.-M.; Cheng, S.H.; Tsai, S.Y.; Leu, S.-Y.; Huang, A.T.

    2002-01-01

    Purpose: To analyze the incidence and risk factors for locoregional recurrence (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1-3 histologically involved axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy (RT). Methods and Materials: Between April 1991 and December 1998, 125 patients with invasive breast cancer were treated with modified radical mastectomy and were found to have 1-3 positive axillary nodes. The median number of nodes examined was 17 (range 7-33). Of the 125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25 months, were included in this study. Sixty-nine patients received adjuvant chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient-related characteristics (age, menopausal status, medial/lateral quadrant of tumor location, T stage, tumor size, estrogen/progesterone receptor protein status, nuclear grade, extracapsular extension, lymphovascular invasion, and number of involved axillary nodes) and treatment-related factors (chemotherapy and hormonal therapy) were analyzed for their impact on LRR. The median follow-up was 54 months. Results: Of 110 patients without RT, 17 had LRR during follow-up. The 4-year LRR rate was 16.1% (95% confidence interval [CI] 9.1-23.1%). All but one LRR were isolated LRR without preceding or simultaneous distant metastasis. According to univariate analysis, age <40 years (p=0.006), T2 classification (p=0.04), tumor size ≥3 cm (p=0.002), negative estrogen receptor protein status (p=0.02), presence of lymphovascular invasion (p=0.02), and no tamoxifen therapy (p=0.0006) were associated with a significantly higher rate of LRR. Tumor size (p=0.006) was the only risk factor for LRR with statistical significance in the multivariate analysis. On the basis of the 4 patient-related factors (age <40 years, tumor ≥3 cm, negative estrogen receptor protein, and lymphovascular invasion), the high-risk group (with 3 or 4

  1. Microencapsulation of tamoxifen: application to cotton fabric.

    Science.gov (United States)

    Ma, Zong-Hui; Yu, Deng-Guang; Branford-White, Christopher J; Nie, Hua-Li; Fan, Zai-Xia; Zhu, Li-Min

    2009-02-15

    Tamoxifen microcapsules and drug loaded medicated fabrics were investigated. The microcapsules were prepared using a complex coacervation procedure involving gelatin B and acacia gum. The morphology, particle size, drug loading capacity and in vitro release characteristics of the drug microcapsules were optimized for coating tamoxifen microcapsules onto the cotton fabrics. Infrared (IR) spectra and SEM were used to characterize the medicated fabrics and air permeability and laundering testing were undertaken to determine the efficiency and effectiveness of the system. Results showed that optimum condition for the microcapsules was at drug/polymer ratio 1:4, polymer concentration 3%, and rate of stirring 1000 rpm. In vitro release assays demonstrated that the tamoxifen was liberated over 10h after an initial bust rate period. SEM images illustrated that the tamoxifen microcapsules were spherical in shape and were also tightly fixed on to the cotton fabrics fast. These observations demonstrate that we have designed and fabricated a medicated system that potentially could be applied within a transdermal drug delivery system and so act in a system for the treatment of breast cancer.

  2. The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Clausen, Mathias Porsmose; Bennetzen, Martin

    2009-01-01

    Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor a-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However, the comp......Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor a-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However......-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen......, suggesting that chlorpromazine enhances the effect of tamoxifen through an estrogen receptor-mediated mechanism. To investigate this putative mechanism, we applied biophysical techniques to simple model membranes in the form of unilamellar liposomes of well-defined composition and found that chlorpromazine...

  3. Effect of botanical immunomodulators on human CYP3A4 inhibition: implications for concurrent use as adjuvants in cancer therapy.

    Science.gov (United States)

    Patil, Dada; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Patwardhan, Bhushan

    2014-03-01

    Many botanical immunomodulators are used as adjuvants along with cancer chemotherapy. However, information on the impact of concurrent administration of such botanicals on pharmacokinetics of chemotherapy agents is inadequate. This study investigates inhibitory activities of 3 popular botanical adjuvants: ASPARAGUS RACEMOSU: (root aqueous extract; ARE), WITHANIA SOMNIFER: (root aqueous extract; WSE), and TINOSPORA CORDIFOLI: (stem aqueous extract, TCE) on human CYP3A4 isoenzyme, responsible for metabolism of several chemotherapy agents. . Testosterone 6-β hydroxylation was monitored using high-performance liquid chromatography as an indicator of CYP3A4 catalytic activities. Ketoconazole (positive control) and extracts were studied at their in vivo-relevant concentrations. TCE showed mild inhibition while no significant inhibitory activities were observed in WSE and ARE. TCE was further fractionated to obtain polar and nonpolar fractions. The nonpolar fraction showed significant CYP3A4 inhibition with IC50 13.06 ± 1.38 µg/mL. Major constituents of nonpolar fraction were identified using HPLC-DAD-MS profiling as berberine, jatrorrhizine, and palmatine, which showed IC50 values as 6.25 ± 0.30, 15.18 ± 1.59, and 15.53 ± 1.89 µg/mL, respectively. Our findings suggest that constituents of TCE extract especially protoberberine alkaloids have the potential to interact with cancer chemotherapy agents that are metabolized by CYP3A4 in vivo.

  4. Iron chelation: an adjuvant therapy to target metabolism, growth and survival of murine PTEN-deficient T lymphoma and human T lymphoblastic leukemia/lymphoma.

    Science.gov (United States)

    Benadiba, Joy; Rosilio, Celia; Nebout, Marielle; Heimeroth, Vera; Neffati, Zouhour; Popa, Alexandra; Mary, Didier; Griessinger, Emmanuel; Imbert, Véronique; Sirvent, Nicolas; Peyron, Jean-François

    2017-06-01

    Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis. Interestingly, DFO displayed synergistic activity with three ALL-specific drugs: dexamethasone, doxorubicin, and L-asparaginase. DFO appeared to act through a reactive oxygen species-dependent DNA damage response and potentiated the action of an inhibitor of the PARP pathway of DNA repair. Our results demonstrate that targeting iron metabolism could be an interesting adjuvant therapy for acute lymphoblastic leukemia.

  5. Reversible, PET-positive, generalized lymphadenopathy and splenomegaly during high-dose interferon-alpha-2b adjuvant therapy for melanoma.

    Science.gov (United States)

    Ridolfi, Laura; Cangini, Delia; Galassi, Riccardo; Passardi, Alessandro; Marzullo, Annamaria; Moretti, Andrea; Framarini, Massimo; Tauceri, Francesca; Serra, Luigi; Chiarion-Sileni, Vanna; Ridolfi, Ruggero

    2008-09-01

    A patient with resected stage III nodular melanoma treated with high-dose interferon-alpha-b2 adjuvant therapy went on to develop generalized lymphadenopathy and splenomegaly. The total body positron emission tomography showed a high F-fluorodeoxyglucose uptake (standardized uptake values >9), indicating possible lymph node and spleen malignancies. Histologic examinations of an axillary lymph node biopsy and an osteomedullar biopsy were negative, excluding both melanoma metastases and hematopoietic tumors. The symptoms completely regressed after suspension of treatment and a follow-up positron emission tomography was negative. It remains to be seen whether this unusual event can be ascribed to an autoimmune phenomenon linked to potential treatment efficacy and survival.

  6. Hyperbaric Oxygen Therapy is Ineffective as an Adjuvant to Daptomycin with Rifampicin Treatment in a Murine Model of Staphylococcus aureus in Implant-Associated Osteomyelitis

    DEFF Research Database (Denmark)

    Jørgensen, Nis Pedersen; Hansen, Kasper; Andreasen, Caroline Marie

    2017-01-01

    therapy. The effect of HBOT on the treatment outcomes of daptomycin and rifampicin against implant-associated osteomyelitis was quantified in a murine model. In total, 80 mice were randomized into two groups receiving antibiotics, either alone or in combination with daily intermittent HBOT (304 kPa for 60......Implant-associated infections caused by bacterial biofilms are difficult to treat. Surgical intervention is often necessary to cure the patient, as the antibiotic recalcitrance of biofilms renders them untreatable with conventional antibiotics. Intermittent hyperbaric oxygen treatment (HBOT) has...... been proposed as an adjuvant to conventional antibiotic treatment and it has been speculated that combining HBOT with antibiotics could improve treatment outcomes for biofilm infections. In this study we addressed whether HBOT could improve treatment outcomes of daptomycin and rifampicin combination...

  7. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

    DEFF Research Database (Denmark)

    Martin, Miguel; Holmes, Frankie A; Ejlertsen, Bent

    2017-01-01

    BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a proto...

  8. FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Lukasz Turczyk

    2017-10-01

    Full Text Available Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa. Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.

  9. Construction of a Nanodiamond–Tamoxifen Complex as a Breast Cancer Drug Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Linda-Lucila Landeros-Martínez

    2016-01-01

    Full Text Available According to the World Health Organization, breast cancer represents 16% of all cancer cases in women and is the second most common cancer. In the past decades, the mortality among patients with metastasis breast cancer has been reduced significantly via drug delivery by means of nanodiamond therapies, which are both biocompatible and scalable. In this study, we determined a theoretical pathway for the construction of a nanodiamond–tamoxifen complex that will act as a drug delivery vehicle for targeting tumor tissues of breast cancer. The tamoxifen pharmacophore was defined and the binding zone was identified for the electrostatic interaction between tamoxifen and a functionalized site of a nanodiamond particle allowing for attachment of the payload (this drug to the surface of the nanodiamond particle. In addition, an analysis of the intermolecular interaction between the nanodiamond and tamoxifen was conducted, showing three hydrogen bonds complying fully with Lipinski’s rule of five, which states that a compound should have five or fewer hydrogen bonds to be permeating and easily absorbed by the body (qualitative prediction. All calculations were performed using the conceptual Density Functional Theory with the M06 functional and the basis set 6-31G(d. The solvent effect has been taken into account by an implicit model, the conductor like polarizable continuum model.

  10. Methotrexate and erythro-9-(2-hydroxynon-3-yl) adenine therapy for rat adjuvant arthritis and the effect of methotrexate on in vivo purine metabolism.

    Science.gov (United States)

    Baggott, Joseph E; Morgan, Sarah L

    2007-06-01

    The objectives were: (1) to test the association of methotrexate (MTX) efficacy in rat adjuvant arthritis (rat AA) with interference of purine biosynthesis and adenosine metabolism and (2) to test the efficacy of erythro-9-(2-hydroxynon-3-yl) adenine (EHNA), an inhibitor of adenosine deaminase, and the efficacy of aminoimidazolecarboxamide (AICA) riboside plus MTX in rat AA. Radiographic and histologic examinations of the hind limbs were measures of efficacy. Urinary excretions of AICA and adenosine were markers of AICA ribotide transformylase inhibition (i.e., blockage of purine biosynthesis) and interference with adenosine metabolism, respectively. AICA and adenosine excretions increased during the day of MTX dosing (treatment day) compared to the previous baseline day in animals responding well to MTX (i.e., low radiographic and histologic scores). Based on radiographic and histologic scores, adjuvant injected rats were separated into two disease categories (i.e., no/mild and moderate/severe). Only AICA excretion was significantly elevated on the treatment day in rat AA with no/mild disease (i.e., those responding well to MTX therapy). AICA (not adenosine) excretion was significantly correlated with the above scores. EHNA was not efficacious, even at toxic levels, while AICA riboside potentiated the efficacy of MTX. The data suggests that efficacious MTX therapy in rat AA (1) blocks purine biosynthesis; (2) increases in in vivo AICA levels. Also adenosine accumulation and blockage of adenosine deaminase (i.e., by EHNA) appear to be less critical to MTX efficacy. Increased levels of AICA metabolites may suppress the immune response in rat AA.

  11. Quality of life in the intergroup exemestane study: a randomized trial of exemestane versus continued tamoxifen after 2 to 3 years of tamoxifen in postmenopausal women with primary breast cancer.

    Science.gov (United States)

    Fallowfield, Lesley J; Bliss, Judith M; Porter, Lucy S; Price, Miranda H; Snowdon, Claire F; Jones, Stephen E; Coombes, R Charles; Hall, Emma

    2006-02-20

    To compare and describe the quality of life (QOL) of women allocated to tamoxifen or exemestane within the Intergroup Exemestane Study (IES). Postmenopausal women with primary breast cancer who were disease free after 2 to 3 years were randomly assigned to switch from tamoxifen to exemestane or continue with tamoxifen until 5 years of treatment were completed. A subset of IES centers participated in a QOL substudy. The Functional Assessment of Cancer Therapy-Breast (FACT-B) and endocrine subscale (ES) were administered before random assignment and at predefined follow-up times. The primary end point was the FACT-B composite Trial Outcome Index (TOI). Secondary end points included total FACT-B+ES score, total ES score, and severity of individual endocrine symptoms. This analysis reports QOL up to 24 months. Five hundred eighty-two patients from eight countries were enrolled onto the substudy. Completion and return of questionnaires was excellent, with 85% available for analysis. QOL was generally good and stable over 2 years, with no clinically meaningful differences found between groups in TOI or ES. Prevalence of severe endocrine symptoms at trial entry was high for vasomotor complaints and sexual problems, which persisted for both groups during the study. No significant differences between groups were seen for any endocrine symptoms apart from vaginal discharge, which was more pronounced with tamoxifen (P < .001). The switch from tamoxifen to exemestane neither increased nor decreased endocrine symptoms present after 2 to 3 years of tamoxifen; the switch also did not initiate significant reports of new symptoms. Results indicate that the clinical benefits of exemestane over tamoxifen are achieved without significant detrimental effect on QOL.

  12. Use of probiotics as an adjuvant to sequential H. pylori eradication therapy: impact on eradication rates, treatment resistance, treatment-related side effects, and patient compliance.

    Science.gov (United States)

    Çekin, Ayhan Hilmi; Şahintürk, Yasin; Akbay Harmandar, Ferda; Uyar, Seyit; Yolcular, Başak Oğuz; Çekin, Yeşim

    2017-01-01

    To evaluate the effect of probiotics administered as an adjuvant to sequential Helicobacter pylori (H. pylori) eradication therapy on treatment outcome and patient compliance. In total, 159 patients with H. pylori infection receiving sequential H. pylori eradication therapy were included in this randomized placebo-controlled study. Starting from day 0 of sequential eradication therapy (ERA), patients in the ERA+probiotic group [n=53, mean (SD) age: 47.7 (14.0) years, 54.7% were females] also received a probiotic supplement with Bifidobacterium animalis subsp. lactis B94 (1 capsule/day), patients in the ERA+placebo group [n=52, mean (SD) age: 46.4 (13.4) years, 51.9% were males] received placebo treatment (1 capsule/day), and patients in the ERA-only group [n=54, mean (SD) age: 46.3 (11.9) years, 55.6% were females] received no additional treatments. Eradication rates, patient compliance, and side effects of eradication therapy were recorded in each treatment group. Significantly higher eradication rates were noted in the ERA+probiotic group (86.8% vs. 70.8%, p=0.025) than in the combined ERA (ERA-only and ERA-placebo) group. Non-compliance with anti-H. pylori treatment was noted in 24 (15.1%) of 159 patients. Lower rates of first week treatment non-compliance due to diarrhea (1.88% vs. 12.26%, p=0.036) were noted in the ERA+probiotic group than in the combined ERA (ERA-only and ERA-placebo) group. Treatment resistance (p: 0.389) was similar between the groups, indicating pure antibiotic resistance without any compliance problems. The number needed to treat for an additional beneficial outcome (NNTB) was 6.2 (CI 95%, 3.5 to 28.9) for probiotic use. In conclusion, adjuvant administration of probiotic (B. animalis subsp. lactis) in 2-week sequential H. pylori eradication therapy is associated with a higher H. pylori eradication rate, lower first week diarrhea-related treatment discontinuation rates, less common self-reported side effects, and higher treatment

  13. Tumorigenic Effects of Tamoxifen on the Female Genital Tract

    Directory of Open Access Journals (Sweden)

    Kaei Nasu M.D., Ph.D.

    2008-01-01

    Full Text Available Tamoxifen is widely used for endocrine treatment and breast cancer prevention. It acts as both an estrogen antagonist in breast tissue and an estrogen agonist in the female lower genital tract. Tamoxifen causes severe gynecologic side effects, such as endometrial cancer. This review focuses on the effects of prolonged tamoxifen treatment on the human female genital tract and considers its tumorigenicity in the gynecologic organs through clinical data analysis. Tamoxifen is associated with an increased incidence of benign endometrial lesions such as polyps and hyperplasia and a two- to four-fold increased risk of endometrial cancer in postmenopausal patients. Moreover, the incidence of functional ovarian cysts is significantly high in premenopausal tamoxifen users. To prevent tamoxifen from having severe side effects in gynecologic organs, frequent gynecological examination should be performed for both premenopausal and postmenopausal patients with breast cancer who are treated with this drug.

  14. Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG Study

    Directory of Open Access Journals (Sweden)

    Arie Figer, Aviram Nissan, Adi Shani, Riva Borovick, Mariana Stiener, Mario Baras, Herbert R. Freund, Aaron Sulkes, Alexander Stojadinovic, Tamar Peretz

    2011-01-01

    Full Text Available Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC. This study evaluates long-term (10-year outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV or 5-FU/Levamisole (5FU+LEV.Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months.Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02 and gastrointestinal toxicity with 5FU+LV (p=0.03. Female patients treated with 5FU+LEV had improved overall survival.Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

  15. The effect of adjuvant N-acetylcysteine effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable COPD

    Directory of Open Access Journals (Sweden)

    Gui-Fang Hu1

    2017-05-01

    Full Text Available Objective: To study the effect of adjuvant N-acetylcysteine (NAC effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable chronic obstructive pulmonary disease (COPD. Methods: Patients with stable COPD treated in Zigong Third People’s Hospital and West China Hospital, Sichuan University between May 2014 and October 2016 were selected and randomly divided into two groups, NAC group received N-acetylcysteine effervescent tablets combined with routine treatment, and control group received routine treatment. Before treatment as well as 2 weeks and 4 weeks after treatment, oxidative stress indexes and airway remodeling indexes in serum as well as inflammatory response indexes in peripheral blood were determined. Results: MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum as well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of both groups of patients after treatment were significantly lower than those before treatment while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those before treatment, and MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum a well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of NAC group after treatment were significantly lower than those of control group while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those of control group. Conclusion: Adjuvant NAC effervescent tablets treatment of stable COPD can improve the effect of oxidative stress and inflammatory response on cardiopulmonary function, and inhibit the airway remodeling caused by protease activation.

  16. Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

    Energy Technology Data Exchange (ETDEWEB)

    Creutzberg, Carien L., E-mail: c.l.creutzberg@lumc.nl [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Stiphout, Ruud G.P.M. van [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands); Nout, Remi A. [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Lutgens, Ludy C.H.W. [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands); Jürgenliemk-Schulz, Ina M. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Jobsen, Jan J. [Department of Radiotherapy, Medisch Spectrum Twente, Enschede (Netherlands); Smit, Vincent T.H.B.M. [Department of Pathology, Leiden University Medical Center, Leiden (Netherlands); Lambin, Philippe [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands)

    2015-03-01

    Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variables which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT

  17. [Effect of the estrogen antagonist tamoxifen in the treatment of advanced mastocarcinoma (author's transl)].

    Science.gov (United States)

    Szepesi, T; Kärcher, K H

    1977-12-01

    Today the endocrin therapy of the advanced mastocarcinoma is in common use. Besides the already known therapy by estrogens, androgens, gestagens, and steroids, Tamoxifen, and estrogen antagonist, is a very promising therapeutic drug. In the presented study, Tamoxifen was submitted to a critical clinical control during a period of one year from 1st October 1975 until 1st October 1976. After a three months' treatment, a rate of 41% of objective remissions could be obtained. The criteria of success were estimated according to the scheme of Karnofsky. The average remission time is 5,5 months. By a determination of the estrogen receptors it would be possible to realize a therapeutic selection and to achieve a higher remission rate. The authors made an interesting observation, i.e. a probably immuno-stimulating effect which, however, still has to be submitted to further examinations. The side effects are described in detail and the indications are established. Its is astonishing that the subjective ameliorations, i.e. cessation of pains in case of generalized formation of metastases in the bones are much more frequent than the objective remissions. We came to the conclusion that the treatment by Tamoxifen is a valuable alternative in the therapy of the mastocarcinoma, above all in the postmenopausal period if the disease is advanced and incurable.

  18. Adjuvant Bisphosphonates for Postmenopausal Breast Cancer

    Science.gov (United States)

    A summary of a meta-analysis of randomized trials of bisphosphonates as adjuvant therapy for women with early-stage breast cancer that shows the drugs can reduce the rate of disease recurrence in bone.

  19. Evaluation of the Role of Monocular Video Game Play as an Adjuvant to Occlusion Therapy in the Management of Anisometropic Amblyopia.

    Science.gov (United States)

    Singh, Archita; Sharma, Pradeep; Saxena, Rohit

    2017-07-01

    To evaluate the role of monocular video game play as an adjuvant to occlusion therapy in the treatment of anisometropic amblyopia. In a prospective randomized study design, 68 children with ages ranging from 6 to 14 years who had anisometropic amblyopia with a best corrected visual acuity (BCVA) in the amblyopic eye of better than 6/36 and worse than 6/12 and no manifest strabismus were recruited. They were randomly allocated into two groups: 34 children received 1 hour per day of video game play for the first month plus 6 hours per day of occlusion therapy (video game and occlusion group) and 34 children received 6 hours per day of occlusion therapy alone (occlusion only group). Patients were then evaluated at baseline and 1 and 3 months after treatment for BCVA, stereoacuity, and contrast sensitivity. In the video game and occlusion group, BCVA improved from 0.61 ± 0.12 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.51 ± 0.14 logMAR (P = .001) at 1 month and 0.40 ± 0.15 logMAR (P = .001) at 3 months. In the occlusion only group, BCVA improved from 0.65 ± 0.09 logMAR at baseline to 0.60 ± 0.10 logMAR (P = .001) at 1 month and 0.48 ± 0.10 logMAR (P = .001) at 3 months. There was significantly more improvement in the video game and occlusion group compared to the occlusion only group (P = .003 at 1 month and P = .027 at 3 months). Video game play plus occlusion therapy enhances the visual recovery in anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus. 2017;54(4):244-249.]. Copyright 2017, SLACK Incorporated.

  20. Long-term results of adjuvant hormonal therapy plus radiotherapy following radical prostatectomy for patients with pT3N0 or pT3N1 prostate cancer

    International Nuclear Information System (INIS)

    Miyake, Hideaki; Sakai, Iori; Harada Ken-ichi; Eto, Hiroshi; Hara, Isao

    2004-01-01

    The objective of the present study was to evaluate the efficacy of adjuvant androgen suppression in conjunction with external beam irradiation after radical prostatectomy in patients with pathologically confirmed extraprostatic disease. Between July 1988 and October 1999, 38 patients with pT3N0 or pT3N1 prostate cancer received adjuvant hormonal therapy and external beam irradiation following radical retropubic prostatectomy and pelvic lymphadenectomy. Administration of luteinizing hormone-releasing hormone analog or castration were initiated as an adjuvant androgen suppression within 4 weeks after surgery, whereas pelvic irradiation was performed at a median dose of 50 G within 3 months after surgery. The prognostic advantage of this combined adjuvant therapy was analyzed. During the median observation period of 92 months, biochemical recurrence occurred in four of the 38 patients and five patients died. Of these five patients, only one died of prostate cancer progression. The 10-year biochemical recurrence-free, cancer-specific and overall survival rates of the 38 patients were 86.7%, 90.9% and 78.7%, respectively. Among several factors examined, only tumor grade was significantly associated with biochemical recurrence-free survival in these patients; however, there were no factors that were independent predictors for biochemical recurrence, based on multivariate analysis. Furthermore, biochemical recurrence-free survival in the 38 patients was significantly superior to that in 54 patients with locally advanced disease who did not receive any postoperative therapies until biochemical recurrence; however, there was no significant difference in cancer-specific and overall survival between these two groups. Despite retrospective analysis with a relatively small number of patients, results of the present study suggest favorable effects of the combined adjuvant treatments with androgen ablation and pelvic irradiation on cancer control for patients with pT3N0 or pT3N1

  1. The Adoption of New Adjuvant Radiation Therapy Modalities Among Medicare Beneficiaries With Breast Cancer: Clinical Correlates and Cost Implications

    International Nuclear Information System (INIS)

    Roberts, Kenneth B.; Soulos, Pamela R.; Herrin, Jeph; Yu, James B.; Long, Jessica B.; Dostaler, Edward

    2013-01-01

    Purpose: New radiation therapy modalities have broadened treatment options for older women with breast cancer, but it is unclear how clinical factors, geographic region, and physician preference affect the choice of radiation therapy modality. Methods and Materials: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify women diagnosed with stage I-III breast cancer from 1998 to 2007 who underwent breast-conserving surgery. We assessed the temporal trends in, and costs of, the adoption of intensity modulated radiation therapy (IMRT) and brachytherapy. Using hierarchical logistic regression, we evaluated the relationship between the use of these new modalities and patient and regional characteristics. Results: Of 35,060 patients, 69.9% received conventional external beam radiation therapy (EBRT). Although overall radiation therapy use remained constant, the use of IMRT increased from 0.0% to 12.6% from 1998 to 2007, and brachytherapy increased from 0.7% to 9.0%. The statistical variation in brachytherapy use attributable to the radiation oncologist and geographic region was 41.4% and 9.5%, respectively (for IMRT: 23.8% and 22.1%, respectively). Women undergoing treatment at a free-standing radiation facility were significantly more likely to receive IMRT than were women treated at a hospital-based facility (odds ratio for IMRT vs EBRT: 3.89 [95% confidence interval, 2.78-5.45]). No such association was seen for brachytherapy. The median radiation therapy cost per treated patient increased from $5389 in 2001 to $8539 in 2007. Conclusions: IMRT and brachytherapy use increased substantially from 1998 to 2007; overall, radiation therapy costs increased by more than 50%. Radiation oncologists played an important role in treatment choice for both types of radiation therapy, whereas geographic region played a bigger role in the use of IMRT than brachytherapy

  2. Which patients benefit most from adjuvant aromatase inhibitors?

    DEFF Research Database (Denmark)

    Viale, G; Regan, M M; Dell'Orto, P

    2011-01-01

    On average, aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy for postmenopausal women with endocrine-responsive early breast cancer. Because there may be contraindications to their use based on side-effects or cost, we investigated subgroups in which aroma...

  3. Colonic healing: the effect of irradiation and chemotherapy - an experimental study, resembling adjuvant therapy for colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Weiber, S.

    1993-08-01

    Adjuvant treatment of colon and rectal carcinoma is of major interest. Irradiation and chemotherapy are modalities used widely. The purpose of this study was to evaluate the effect of preoperative irradiation and postoperative intraperitoneal 5-fluorouracil treatment on colonic healing. In rats preoperative irradiation of the lower abdominal region by 10 + 10 Gy four days apart caused inflammatory reaction in the colon as evaluated by histology and determination of myeloperoxidase activity. The inflammatory reaction reached its peek within a week of the second irradiation. When standard used colonic resections and anastomes were performed within the irradiate part of the colon the anastomotic healing was not affected during the first week after operation as judged by complications and breaking strength. A lower breaking strength and an increase in myeloperoxidase activity two months after operation may indicate late changes within the intestinal wall. Intraperitoneal 5-fluorouracil in rat given immediately after colonic resection and repeated as daily injections caused a weight loss and marked reduction in breaking strength of the anastomosis as well as in the abdominal skin wound. A reduction in 5-fluorouracil concentration did not alter the negative wound healing effect of the chemotherapy. In a group of rats subjected to nutritional depletion, mimicking the weight curve of 5-fluorouracil treated animals, anastomotic breaking strength was not compromised to the same extent as when 5-fluorouracil was given. This indicated a direct toxic effect rather than an effect of reduced food intake caused by 5-FU treatment. Collagen synthesis and the formation of new tissue in the wound gap was reduced in 5-fluorouracil treated animals compared to controls as judged by in vivo incorporation of {sup 3}H-proline in the anastomotic segment and determination of anastomotic breaking strength after removal of sutures. 108 refs.

  4. Colonic healing: the effect of irradiation and chemotherapy - an experimental study, resembling adjuvant therapy for colorectal carcinoma

    International Nuclear Information System (INIS)

    Weiber, S.

    1993-08-01

    Adjuvant treatment of colon and rectal carcinoma is of major interest. Irradiation and chemotherapy are modalities used widely. The purpose of this study was to evaluate the effect of preoperative irradiation and postoperative intraperitoneal 5-fluorouracil treatment on colonic healing. In rats preoperative irradiation of the lower abdominal region by 10 + 10 Gy four days apart caused inflammatory reaction in the colon as evaluated by histology and determination of myeloperoxidase activity. The inflammatory reaction reached its peek within a week of the second irradiation. When standard used colonic resections and anastomes were performed within the irradiate part of the colon the anastomotic healing was not affected during the first week after operation as judged by complications and breaking strength. A lower breaking strength and an increase in myeloperoxidase activity two months after operation may indicate late changes within the intestinal wall. Intraperitoneal 5-fluorouracil in rat given immediately after colonic resection and repeated as daily injections caused a weight loss and marked reduction in breaking strength of the anastomosis as well as in the abdominal skin wound. A reduction in 5-fluorouracil concentration did not alter the negative wound healing effect of the chemotherapy. In a group of rats subjected to nutritional depletion, mimicking the weight curve of 5-fluorouracil treated animals, anastomotic breaking strength was not compromised to the same extent as when 5-fluorouracil was given. This indicated a direct toxic effect rather than an effect of reduced food intake caused by 5-FU treatment. Collagen synthesis and the formation of new tissue in the wound gap was reduced in 5-fluorouracil treated animals compared to controls as judged by in vivo incorporation of 3 H-proline in the anastomotic segment and determination of anastomotic breaking strength after removal of sutures. 108 refs

  5. Preliminary results of the use of photon-magnetic therapy in prevention and treatment of skin radiation reactions of patients with breast cancer with adjuvant radiation therapy

    International Nuclear Information System (INIS)

    Syimonova, L.Yi.; Gertman, V.Z.; Byilogurova, L.V.; Kulyinyich, G.V.; Lavrik, V.P.

    2012-01-01

    The authors report preliminary findings of the investigation of the effect of combination photon-magnetic therapy with successive application of red and blue light to the skin of breast cancer patients during the course of post-operative radiation therapy. It was established that photonmagnetic therapy positively influenced the state of the skin in the irradiated areas. Addition of the magnetic factor significantly improved the efficacy of phototherapy. The patients receiving photon-magnetic therapy finished the course of radiation therapy with almost unchanged skin.

  6. Limb sparing approach: Adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma

    International Nuclear Information System (INIS)

    Merimsky, Ofer; Soyfer, Vjacheslav; Kovner, Felix; Bickels, Jacob; Issakov, Josephine; Flusser, Gideon; Meller, Isaac; Ofer, Oded; Kollender, Yehuda

    2005-01-01

    Background: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). Patients and methods: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. Results: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. Conclusions: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory

  7. EFFICACY OF SPINAL-CORD STIMULATION AS ADJUVANT THERAPY FOR INTRACTABLE ANGINA-PECTORIS - A PROSPECTIVE, RANDOMIZED CLINICAL-STUDY

    NARCIS (Netherlands)

    DEJONGSTE, MJL; HAUTVAST, RWM; HILLEGE, HL; LIE, KI

    Objectives. In a prospective, randomized study with an 8-week follow-up period, we evaluated the efficacy of spinal cord stimulation an exercise capacity and quality of life in patients with intractable angina. Background. Despite important achievements in therapy for ischemic heart disease, there

  8. Tamoxifen Pharmacovigilance: Implications for Safe Use in the Future.

    Science.gov (United States)

    Antimisiaris, Demetra; Bae, Ki-Hwan Gabriel; Morton, Laura; Gully, Zahara

    2017-09-01

    To survey the status of current tamoxifen pharmacovigilance documentation reflecting tamoxifen use in an academic outpatient multispecialty practice in older adults. This data will help provide information to develop improved pharmacovigilance for a growing cohort of older adult users. The data will be utilized by an interdisciplinary team developing new methods of identifying factors for individualized pharmacovigilance in older adults. Retrospective chart review to gather descriptive and quantitative data on tamoxifen pharmacovigilance. Multi-specialty clinic. Ninety-three patients 60 years of age and older. Quantitative report of tamoxifen monitoring as well as descriptive analysis of individual cases. We found 19 cases of serious adverse events possibly related to tamoxifen (thrombi, uterine malignancies). There were 15 cases with no documentation of pharmacovigilance. All cases had incomplete pharmacovigilance documented. There were two cases of hypercalcemia. There was one case of tamoxifen discontinuation resulting from muscle pain and with chronic muscle pain complaints while receiving tamoxifen. We observed a correlation in older age or high comorbidity burden patients and adverse events patients. Some studies direct the important pharmacovigilance toward prevention of thrombi, uterine malignancies, and hypercalcemia; however, it is not easy to identify recommendations for frequency or focus of monitoring to prevent adverse events for individual older adults based on existing recommendations. The data collected and presented in this study serve to heighten awareness of tamoxifen pharmacovigilance and as a starting point for the application of machine learning techniques and modeling to identify high-risk patients and individualized pharmacovigilance recommendations.

  9. Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Damast, Shari, E-mail: shari.damast@yale.edu [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goldfarb, Shari [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Eaton, Anne; Patil, Sujata [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Mosenkis, Jeffrey [Department of Comparative Human Development, University of Chicago, Chicago, Illinois (United States); Bennett, Antonia [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Atkinson, Thomas [Department of Psychiatry, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jewell, Elizabeth; Leitao, Mario; Barakat, Richard; Carter, Jeanne [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Basch, Ethan [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2012-10-01

    Purpose: We used the Female Sexual Function Index (FSFI) to investigate the prevalence of sexual dysfunction (SD) and factors associated with diminished sexual functioning in early stage endometrial cancer (EC) patients treated with simple hysterectomy and adjuvant brachytherapy. Methods and Materials: A cohort of 104 patients followed in a radiation oncology clinic completed questionnaires to quantify current levels of sexual functioning. The time interval between hysterectomy and questionnaire completion ranged from <6 months to >5 years. Multivariate regression was performed using the FSFI as a continuous variable (score range, 1.2-35.4). SD was defined as an FSFI score of <26, based on the published validation study. Results: SD was reported by 81% of respondents. The mean ({+-} standard deviation) domain scores in order of highest-to-lowest functioning were: satisfaction, 2.9 ({+-}2.0); orgasm, 2.5 ({+-}2.4); desire, 2.4 ({+-}1.3); arousal, 2.2 ({+-}2.0); dryness, 2.1 ({+-}2.1); and pain, 1.9 ({+-}2.3). Compared to the index population in which the FSFI cut-score was validated (healthy women ages 18-74), all scores were low. Compared to published scores of a postmenopausal population, scores were not statistically different. Multivariate analysis isolated factors associated with lower FSFI scores, including having laparotomy as opposed to minimally invasive surgery (effect size, -7.1 points; 95% CI, -11.2 to -3.1; P<.001), lack of vaginal lubricant use (effect size, -4.4 points; 95% CI, -8.7 to -0.2, P=.040), and short time interval (<6 months) from hysterectomy to questionnaire completion (effect size, -4.6 points; 95% CI, -9.3-0.2; P=.059). Conclusions: The rate of SD, as defined by an FSFI score <26, was prevalent. The postmenopausal status of EC patients alone is a known risk factor for SD. Additional factors associated with poor sexual functioning following treatment for EC included receipt of laparotomy and lack of vaginal lubricant use.

  10. Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

    International Nuclear Information System (INIS)

    Damast, Shari; Alektiar, Kaled M.; Goldfarb, Shari; Eaton, Anne; Patil, Sujata; Mosenkis, Jeffrey; Bennett, Antonia; Atkinson, Thomas; Jewell, Elizabeth; Leitao, Mario; Barakat, Richard; Carter, Jeanne; Basch, Ethan

    2012-01-01

    Purpose: We used the Female Sexual Function Index (FSFI) to investigate the prevalence of sexual dysfunction (SD) and factors associated with diminished sexual functioning in early stage endometrial cancer (EC) patients treated with simple hysterectomy and adjuvant brachytherapy. Methods and Materials: A cohort of 104 patients followed in a radiation oncology clinic completed questionnaires to quantify current levels of sexual functioning. The time interval between hysterectomy and questionnaire completion ranged from 5 years. Multivariate regression was performed using the FSFI as a continuous variable (score range, 1.2-35.4). SD was defined as an FSFI score of <26, based on the published validation study. Results: SD was reported by 81% of respondents. The mean (± standard deviation) domain scores in order of highest-to-lowest functioning were: satisfaction, 2.9 (±2.0); orgasm, 2.5 (±2.4); desire, 2.4 (±1.3); arousal, 2.2 (±2.0); dryness, 2.1 (±2.1); and pain, 1.9 (±2.3). Compared to the index population in which the FSFI cut-score was validated (healthy women ages 18-74), all scores were low. Compared to published scores of a postmenopausal population, scores were not statistically different. Multivariate analysis isolated factors associated with lower FSFI scores, including having laparotomy as opposed to minimally invasive surgery (effect size, −7.1 points; 95% CI, −11.2 to −3.1; P<.001), lack of vaginal lubricant use (effect size, −4.4 points; 95% CI, −8.7 to −0.2, P=.040), and short time interval (<6 months) from hysterectomy to questionnaire completion (effect size, −4.6 points; 95% CI, −9.3-0.2; P=.059). Conclusions: The rate of SD, as defined by an FSFI score <26, was prevalent. The postmenopausal status of EC patients alone is a known risk factor for SD. Additional factors associated with poor sexual functioning following treatment for EC included receipt of laparotomy and lack of vaginal lubricant use.

  11. The role of the expression of bcl-2, p53 gene in tamoxifen-induced apoptosis of breast cancer cells and its relationship with hormone receptor status

    International Nuclear Information System (INIS)

    Noh, Woo Chul; Ham, Yong Ho

    1998-01-01

    To investigate the relationship of bcl-2, p53, ER and tamoxifen-induced apoptosis of breast cancer cells, MCF-7 (ER+/bcl-2+/p53-) and MB MDA 468 (ER-/bcl-2-/p53+) cell line were cultured in estrogen-free condition. E2(10'-'9M) and tamoxifen (10'-'5M) were added to the media. The changes of bcl-2 and mutant p53 protein were checked by Western blot and apoptosis were measured by flowcytometry. In MCF-7 cells, we found that treatment with tamoxifen resulted in a decrease in bcl-2 protein level, but produced no change in mutant p53. In MB MDA 468 cell however, there were no changes of bcl-2 and mutant p53 protein level when E2 or tamoxifen were added. Apoptotic cells increased with time-dependent pattern when tamoxifen was added to MCF-7 cells. According to these result, ER+/blc-2+/mutant p53- cells, when treated with tamoxifen, were converted into bcl-2/mutant p53- cells which were more prone to apoptosis than bcl-2-/mutant p53+ cells. The paradoxical correlation of bcl-2 and ER which had been observed in clinical studies might be explained with this results and bcl-2 protein seems to be one of important factors that can predict the effect of hormone therapy. (author). 26 refs., 5 figs

  12. Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers.

    Science.gov (United States)

    Chew, G L; Huo, C W; Huang, D; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M C; Hopper, J L; Britt, K; Henderson, M A; Haviv, I; Thompson, E W

    2014-11-01

    Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other

  13. Evaluation of six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon therapy in the He13A/98 multicenter trial

    Directory of Open Access Journals (Sweden)

    Fountzilas George

    2010-11-01

    Full Text Available ABSTRACT Purpose Interferon is approved for adjuvant treatment of patients with stage IIb/III melanoma. The toxicity and uncertainty regarding survival benefits of interferon have qualified its acceptance, despite significant durable relapse prevention in a fraction of patients. Predictive biomarkers that would enable selection of patients for therapy would have a large impact upon clinical practice. Specific CTLA-4 polymorphisms have previously shown an association with response to CTLA-4 blockade in patients with metastatic melanoma and the development of autoimmunity. Experimental design 286 melanoma patients and 288 healthy controls were genotyped for six CTLA-4 polymorphisms previously suggested to be important (AG 49, CT 318, CT 60, JO 27, JO30 and JO 31. Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. Results No significant differences were found between the distributions of CTLA-4 polymorphisms in the melanoma population compared with healthy controls. Relapse free survival (RFS and overall survival (OS did not differ significantly between patients with the alleles represented by these polymorphisms. No correlation between autoimmunity and specific alleles was shown. The six polymorphisms evaluated where strongly associated (Fisher's exact p-values Conclusion No polymorphisms of CTLA-4 defined by the SNPs studied were correlated with improved RFS, OS, or autoimmunity in this high-risk group of melanoma patients.

  14. Adjuvant radiation therapy in uterine carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes.

    Science.gov (United States)

    Manzerova, Julia; Sison, Cristina P; Gupta, Divya; Holcomb, Kevin; Caputo, Thomas A; Parashar, Bhupesh; Nori, Dattatreyudu; Wernicke, A Gabriella

    2016-05-01

    To examine clinical and demographic characteristics of a population-based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns. Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression - to analyze the effect of covariates on survival. 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; pAfrican Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; paRT group: 42 vs. 22 (paRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Personal and clinical social support and adherence to adjuvant endocrine therapy among hormone receptor-positive breast cancer patients in an integrated health care system.

    Science.gov (United States)

    Kroenke, Candyce H; Hershman, Dawn L; Gomez, Scarlett L; Adams, Sara R; Eldridge, Elizabeth H; Kwan, Marilyn L; Ergas, Isaac J; Kubo, Ai; Kushi, Lawrence H

    2018-04-18

    We evaluated associations between personal and clinical social support and non-adherence to adjuvant endocrine therapy (AET) in a large, Northern California breast cancer (BC) cohort from an integrated healthcare network. This study included 3382 women from the Pathways Study diagnosed from 2005 to 2013 with stages I-III hormone receptor-positive BC and who responded to the Medical Outcomes Study Social Support and Interpersonal Processes of Care surveys, approximately 2 months post-diagnosis. We used logistic regression to evaluate associations between tertiles of social support and non-initiation (personal social support (P trend = 0.02). Women with moderate (HR 1.20, 95% CI 0.99-1.45) or low (HR 1.32, 95% CI 1.09-1.60) personal social support were also more likely to discontinue treatment (P trend = 0.01). Furthermore, women with moderate (HR 1.25, 95% CI 1.02-1.53) or low (HR 1.38, 95% CI 1.12-1.70) personal social support had higher non-adherence (P trend = 0.007). Associations with clinical social support and outcomes were similar. Notably, high clinical social support mitigated the risk of discontinuation when patients' personal support was moderate or low (P value = 0.04). Women with low personal or clinical social support had higher AET non-adherence. Clinician teams may need to fill support gaps that compromise treatment adherence.

  16. Cardiovascular event-free survival after adjuvant radiation therapy in breast cancer patients stratified by cardiovascular risk

    International Nuclear Information System (INIS)

    Onwudiwe, Nneka C; Kwok, Young; Onukwugha, Eberechukwu; Sorkin, John D; Zuckerman, Ilene H; Shaya, Fadia T; Daniel Mullins, C

    2014-01-01

    The objective of this study was to estimate the risk of a cardiovascular event or death associated with modern radiation in a population of elderly female breast cancer patients with varying baseline cardiovascular risk. The data used for this analysis are from the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The retrospective cohort study included women aged 66 years and older with stage 0–III breast cancer diagnosed between 2000 and 2005. Women were grouped as low, intermediate, or high cardiovascular risk based on the presence of certain clinical diagnoses. The risk for the combined outcome of a hospitalization for a cardiovascular event or death within 6 months and 24 months of diagnosis was estimated using a multivariable Cox model. The median follow-up time was 24 months. Among the 91,612 women with American Joint Committee on Cancer (AJCC) stage 0–III breast cancer: 39,555 (43.2%) were treated with radiation therapy and 52,057 (56.8%) were not. The receipt of radiation therapy in the first 6 months was associated with a statistically significant increased risk for the combined outcome in women categorized as high risk (HR = 1.510; 95% CI, 1.396–1.634) or intermediate risk (HR = 1.415; 95% CI, 1.188–1.686) but not low risk (HR = 1.027; 95% CI, 0.798–1.321). Women with a prior medical history of cardiovascular disease treated with radiation therapy are at increased risk for an event and should be monitored for at least 6 months following treatment with radiation therapy

  17. Conservative surgery and adjuvant radiation therapy in the management of adult soft tissue sarcoma of the extremities: clinical and radiobiological results

    International Nuclear Information System (INIS)

    Mundt, Arno J.; Awan, Azhar; Sibley, Gregory S.; Simon, Michael; Rubin, Steven J.; Samuels, Brian; Wong, William; Beckett, Michael; Vijayakumar, S.; Weichselbaum, Ralph R.

    1995-01-01

    Purpose: The outcome of adult patients with soft tissue sarcoma of the extremities treated with conservative surgery and adjuvant irradiation was evaluated to (a) determine the appropriate treatment volume and radiation dosage in the postoperative setting, and (b) correlate in vitro radiobiological parameters obtained prior to therapy with clinical outcome. Methods and Materials: Sixty-four consecutive adult patients with soft tissue sarcoma of the extremities (40 lower, 24 upper) who underwent conservative surgery and adjuvant irradiation (7 preoperative, 50 postoperative, 7 perioperative) between 1978 and 1991 were reviewed. The initial radiation field margin surrounding the tumor bed/scar was retrospectively analyzed in all postoperative patients. Initial field margins were < 5 cm in 12 patients, 5-9.9 cm in 32 and ≥ 10 cm in 6. Patients with negative pathological margins were initially treated with traditional postoperative doses (64-66 Gy); however, in later years the postoperative dose was reduced to 60 Gy. Thirteen cell lines were established prior to definite therapy, and radiobiological parameters (multitarget and linear-quadratic) were obtained and correlated with outcome. Results: Postoperative patients treated with an initial field margin of < 5 cm had a 5-year local control of 30.4% vs. 93.2% in patients treated with an initial margin of ≥ 5 cm (p = 0.0003). Five-year local control rates were similar in patients treated with initial field margins of 5-9.9 cm (91.6%) compared with those treated with ≥ 10 cm margins (100%) (p = 0.49). While postoperative patients receiving < 60 Gy had a worse local control than those receiving ≥ 60 Gy (p = 0.08), no difference was seen in local control between patients receiving less than traditional postoperative doses (60-63.9 Gy) (74.4%) vs. those receiving 64-66 Gy (87.0%) (p = 0.5). The local control of patients treated in the later years of the study, with strict attention to surgical and radiotherapeutic

  18. Breast and other cancer dormancy as a therapeutic endpoint: speculative recombinant T cell receptor ligand (RTL) adjuvant therapy worth considering?

    International Nuclear Information System (INIS)

    Bakács, Tibor; Mehrishi, Jitendra N

    2010-01-01

    Most individuals who died of trauma were found to harbour microscopic primary cancers at autopsies. Surgical excision of the primary tumour, unfortunately, seems to disturb tumour dormancy in over half of all metastatic relapses. A recently developed immune model suggested that the evolutionary pressure driving the creation of a T cell receptor repertoire was primarily the homeostatic surveillance of the genome. The model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected T cell receptors and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. The repertoire is maintained by continuous peripheral stimulation via soluble forms of self-peptide-presenting major histocompatibility complex molecules governed by the law of mass action. The model states that foreign peptides inhibit the complementary interactions between the major histocompatibility complexes and T cell receptors. Since the vast majority of clinically detected cancers present self-peptides the model assumes that tumour cells are, paradoxically, under homeostatic T cell control. The novelty of our hypothesis therefore is that resection of the primary tumour mass is perceived as loss of 'normal' tissue cells. Consequently, T cells striving to reconstitute homeostasis stimulate rather than inhibit the growth of dormant tumour cells and avascular micrometastases. Here we suggest that such kick-start growths could be prevented by a recombinant T cell receptor ligand therapy that modifies T cell behaviour through a partial activation mechanism. The homeostatic T cell regulation of tumours can be tested in a tri-transgenic mice model engineered to express potent oncogenes in a doxycycline-dependent manner. We suggest seeding dissociated, untransformed mammary cells from doxycycline naïve mice into the lungs of two mice groups: one

  19. Coffee prevents early events in tamoxifen-treated breast cancer patients and modulates hormone receptor status.

    Science.gov (United States)

    Simonsson, Maria; Söderlind, Viktoria; Henningson, Maria; Hjertberg, Maria; Rose, Carsten; Ingvar, Christian; Jernström, Helena

    2013-05-01

    Whether coffee modulates response to endocrine therapy in breast cancer patients is currently unknown. The CYP1A2 and CYP2C8 enzymes contribute to tamoxifen and caffeine metabolism. The purpose was to investigate the impact of coffee consumption on tumor characteristics and risk for early events in relation to breast cancer treatment and CYP1A2 and CYP2C8 genotypes. Questionnaires regarding lifestyle were completed preoperatively by 634 patients in southern Sweden. CYP1A2*1F and CYP2C8*3 were genotyped. Clinical data and tumor characteristics were obtained from patients' charts, population registries, and pathology reports. Coffee consumption was categorized as low (0-1 cups/day), moderate (2-4 cups/day), or high (5+ cups/day). The proportion of estrogen receptor negative (ER-) tumors increased with increasing coffee consumption (p trend = 0.042). Moderate to high consumption was associated with lower frequency of discordant receptor status (ER + PgR-) OR 0.38 (0.23-0.63) compared to low consumption. Median follow-up time was 4.92 (IQR 3.01-6.42) years. Tamoxifen-treated patients with ER+ tumors (n = 310) who consumed two or more cups/day had significantly decreased risk for early events compared to patients with low consumption, adjusted HR 0.40 (0.19-0.83). Low consumption combined with at least one CYP1A2*1F C-allele (n = 35) or CYP2C8*3 (n = 13) was associated with a high risk for early events in tamoxifen-treated patients compared to other tamoxifen-treated patients, adjusted HRs 3.49 (1.54-7.91) and 6.15 (2.46-15.36), respectively. Moderate to high coffee consumption was associated with significantly decreased risk for early events in tamoxifen-treated patients and modified hormone receptor status. If confirmed, new recommendations regarding coffee consumption during tamoxifen treatment may be warranted.

  20. Deep inspiration breath hold with electromagnetic confirmation of chest wall position for adjuvant therapy of left-sided breast cancer: Technique and accuracy.

    Science.gov (United States)

    Kathpal, Madeera; Tinnel, Brent; Sun, Kelly; Ninneman, Stephanie; Malmer, Cynthia; Wendt, Stacie; Buff, Sheena; Valentich, David; Gossweiler, Marisa; Macdonald, Dusten

    2016-01-01

    With most patients now living long after their breast cancer diagnosis, minimizing long-term side effects of breast cancer treatment, such as reducing late cardiac and pulmonary side effects of radiation therapy (RT), is particularly important. It is now possible to use an electromagnetic tracking system to allow real-time tracking of chest wall (CW) position during the delivery of RT. Here, we report our experience using electromagnetic surface transponders as an added measure of CW position during deep inspiration breath hold (DIBH). We conducted a single-institution institutional review board-approved retrospective review of 15 female left-sided breast cancer patients treated between July 2012 and June 2013 with conventional whole breast radiation. We compared daily port films with treatment planning digitally reconstructed radiographs to establish daily setup accuracy, then used Calypso tracings to compare the position of the CW during the daily port film with the position of the CW during that day's treatment to determine the reproducibility of the breath hold position. Finally, we created competing treatment plans not using DIBH and used a paired t test to compare mean heart (MH) and left anterior descending (LAD) coronary artery dose between the 2 techniques. Mean total error (inter- and intrafraction) was dominated by interfraction error and was greatest in the longitudinal direction with a mean of 2.13 mm and 2 standard deviations of 8.2 mm. DIBH significantly reduced MH and LAD dose versus free breathing plans (MH, 1.26 Gy vs 2.84 Gy, P ≤ .001; LAD, 5.49 Gy vs 18.15 Gy, P ≤ .001). This study demonstrates that DIBH with electromagnetic confirmation of CW position is feasible, and allows potential improvement in the accurate delivery of adjuvant RT therapy for breast cancer. Published by Elsevier Inc.

  1. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

    Directory of Open Access Journals (Sweden)

    Kiss Tamas

    2010-06-01

    Full Text Available Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG is effective in non-muscle-invasive bladder cancer (BC, adverse events (AEs are considerable. Monocyte-derived activated killer cells (MAK are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM® to BCG in patients after transurethral resection (TURB of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM. Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint and prophylactic effects (secondary endpoint were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE, respectively (p Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

  2. Tualang Honey Promotes Apoptotic Cell Death Induced by Tamoxifen in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Nik Soriani Yaacob

    2013-01-01

    Full Text Available Tualang honey (TH is rich in flavonoids and phenolic acids and has significant anticancer activity against breast cancer cells comparable to the effect of tamoxifen (TAM, in vitro. The current study evaluated the effects of TH when used in combination with TAM on MCF-7 and MDA-MB-231 cells. We observed that TH promoted the anticancer activity of TAM in both the estrogen receptor-(ER-responsive and ER-nonresponsive human breast cancer cell lines. Flow cytometric analyses indicated accelerated apoptosis especially in MDA-MB-231 cells and with the involvement of caspase-3/7, -8 and -9 activation as shown by fluorescence microscopy. Depolarization of the mitochondrial membrane was also increased in both cell lines when TH was used in combination with TAM compared to TAM treatment alone. TH may therefore be a potential adjuvant to be used with TAM for reducing the dose of TAM, hence, reducing TAM-induced adverse effects.

  3. Adjuvant therapy with 5-fluorouracil for breast cancer of likely poor prognosis: 15-year results of a randomized trial.

    Science.gov (United States)

    Jack, W J; Everington, D; Rodger, A; Forrest, A P; Stewart, H J

    1995-01-01

    In a trial conducted in southeast Scotland between April 1974 and December 1979, 332 women with invasive breast cancer of Stage I and II with histological evidence of node involvement, or who had operable or inoperable Stage III disease, were randomized, after primary local therapy (mastectomy, node biopsy and radiotherapy for all except the inoperable disease patients who underwent radiotherapy alone) to receive 12 4-weekly intravenous injections of 5-fluorouracil (5-FU), 700 mg/m2 or no systemic therapy. After a median follow-up of 15 years from randomization, no difference is shown between the two groups in terms of distant relapse (hazard ratio (HR) = 1.02; 95% CI 0.78-1.32), event free survival (HR = 1.23; 95% CI 0.97-1.56), or total survival (HR = 1.19; 95% CI 0.93-1.52). Locoregional relapse is significantly reduced by 5-FU administration (HR = 1.88; 95% CI 1.20-2.96). The results are similar for the trial as a whole or when mastectomy patients are considered alone. Toxicity was minimal with marrow suppression in only 19 of 147 patients receiving more than one injection; only five patients discontinued therapy due to nausea and vomiting. However, retrosternal pain occurred in 16 patients, nine of whom had their treatment curtailed as a result. Seventy-seven per cent of patients have died, the majority from breast cancer. Only 1.2% of deaths are considered attributable to cardiac causes of 5-FU is not associated with excess cardiac deaths in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goody, Rebecca B. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); MacKay, Helen [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Pitcher, Bethany [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Oza, Amit; Siu, Lillian L. [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kim, John; Wong, Rebecca K.S. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Chen, Eric [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Swallow, Carol [Department of Surgical Oncology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Canada); Knox, Jennifer [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kassam, Zahra [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket, Ontario (Canada); Cummings, Bernard [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Feld, Ron; Hedley, David; Liu, Geoffrey; Krzyzanowska, Monika K. [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Dinniwell, Robert; Brade, Anthony M.; Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Pintilie, Melania [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); and others

    2016-12-01

    Purpose: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. Methods and Materials: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m{sup 2}/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m{sup 2}) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. Results: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m{sup 2} cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. Conclusion: Cisplatin can be safely delivered with 5-FU–based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.

  5. Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer

    International Nuclear Information System (INIS)

    Goody, Rebecca B.; MacKay, Helen; Pitcher, Bethany; Oza, Amit; Siu, Lillian L.; Kim, John; Wong, Rebecca K.S.; Chen, Eric; Swallow, Carol; Knox, Jennifer; Kassam, Zahra; Cummings, Bernard; Feld, Ron; Hedley, David; Liu, Geoffrey; Krzyzanowska, Monika K.; Dinniwell, Robert; Brade, Anthony M.; Dawson, Laura A.; Pintilie, Melania

    2016-01-01

    Purpose: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. Methods and Materials: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m 2 /day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m 2 ) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. Results: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m 2 cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. Conclusion: Cisplatin can be safely delivered with 5-FU–based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.

  6. The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

    International Nuclear Information System (INIS)

    Fowble, B.; Fein, D.A.; Hanlon, A.L.; Eisenberg, B.L.; Hoffman, J.P.; Sigurdson, E.R.; Daly, M.B.; Goldstein, L.J.

    1995-01-01

    Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

  7. Adjuvant Therapy with Silibinin Improves the Efficacy of Paclitaxel and Cisplatin in MCF-7 Breast Cancer Cells

    Science.gov (United States)

    Chavoshi, Hadi; Vahedian, Vahid; Saghaei, Somaiyeh; Pirouzpanah, Mohammad Bagher; Raeisi, Mortaza; Samadi, Nasser

    2017-08-27

    Herbal-derived medicines have introduced as sources of novel drugs due to minimum systemic side effects. Silibinin as a flavonoid compound has showed with effective chemotherapeutic effects on different cancers. Here, we investigated the impact of combination therapy of silibinin, with paclitaxel and cisplatin in inhibition of proliferation and induction of apoptosis in MCF-7 cells. Cell proliferation was assessed by MTT assay and the percentage of apoptotic cells was measured using flowcytometric assay. Understand of molecular mechanism of this combination related to apoptotic pathway were evaluated by Real Time RT-PCR assays. The IC50 values for silibinin, paclitaxel and cisplatin were 160 ± 22.2 μM, 33.7 ± 4.2 nM and 3.2 ± 0.5 μM, respectively. Paclitaxel and cisplatin induced higher percentage of apoptosis in MCF-7 (P < 0.05). Treatment of cell line with combination of silibinin and paclitaxel or cisplatin showed enhanced early apoptosis 56% and 61%, respectively (P < 0.05). Gene expression patterns demonstrated a significant decrease in anti-apoptotic Bcl-2 with increase in pro-apoptotic Bax, P53, BRCA1 and ATM mRNA levels. Taken together combination therapy of breast cancer cells by applying paclitaxel or cisplatin with silibinin synergistically increases the anti-proliferative effect of single agents. Creative Commons Attribution License