Báo cáo hóa học: A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899
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Báo cáo hóa học: "A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899"DiPaola et al. Journal of Translational Medicine 2010, 8:20http://www.translational-medicine.com/content/8/1/20 RESEARCH Open AccessA randomized phase II trial of mitoxantrone,estramustine and vinorelbine or bcl-2 modulationwith 13-cis retinoic acid, interferon and paclitaxelin patients with metastatic castrate-resistantprostate cancer: ECOG 3899Robert S DiPaola1*, Yu-Hui Chen2, Mark Stein1, David Vaughn3, Linda Patrick-Miller1, Michael Carducci4,Bruce Roth5, Eileen White6, George Wilding7 Abstract Background: To test the hypothesis that modulation of Bcl-2 with 13-cis retinoic acid (CRA)/interferon-alpha2b (IFN) with paclitaxel (TAX), or mitoxantrone, estramustine and vinorelbine (MEV) will have clinical activity in men with metastatic castrate-resistant prostate cancer (CRPC). Methods: 70 patients were treated with either MEV (Arm A) in a 3-week cycle or CRA/IFN/TAX with an 8-week cycle (Arm B). Patients were assessed for response, toxicity, quality of life (QOL), and the effect of treatment on Bcl- 2 levels in peripheral blood mononuclear cells (PBMC). Results: The PSA response rates were 50% and 23%, measurable disease response rates (CR+PR) 14% and 15%, and median overall survival 19.4 months and 13.9 months on Arm A and Arm B respectively. Transient grade 4 neutropenia occurred in 18 and 2 patients, and grade 3 to 4 thrombosis in 7 patients and 1 patient in Arm A and Arm B respectively. Patients on Arm B reported a clinically significant decline in QOL between baseline and week 9/10 (.71 s.d.), and a significantly lower level of QOL than Arm A (p = 0.01). As hypothesized, Bcl-2 levels decreased with CRA/IFN therapy only in Arm B (p = 0.03). Conclusions: Treatment with MEV was well tolerated and demonstrated clinical activity in patients with CRPC. Given the adverse effect of CRA/IFN/TAX on QOL, the study of other novel agents that target Bcl-2 family proteins is warranted. The feasibility of measuring Bcl-2 protein in a cooperative group setting is hypothesis generating and supports further study as a marker for Bcl-2 targeted therapy. Trial Registration: Clinical Trials Registration number: CDR0000067865Background are limited with only data clearly established for the useIt was estimated that approximately 200,000 new patients of docetaxel chemotherapy [2].were diagnosed with prostate cancer, and 40,000 died An important mechanism of tumor resistance, whichfrom their disease in 2008 [1]. Standard hormonal ther- can be exploited therapeutically, is the over-expression ofapy or chemotherapy is limited in effectiveness against Bcl-2. The over-expression of Bcl-2 is implicated as ametastatic prostate cancer because of the development of cause of hormonal and chemotherapy resistance and hastumor resistance. Options for improved survival in been shown to increase with castration in prostate cancerpatients with castrate-resistant prostate cancer (CRPC) [3,4]. Prior studies conducted by our group and other investigators demonstrated that retinoids can decrease expression of Bcl-2, that the combination of 13-cis reti-* Correspondence: dipaolrs@umdnj.edu1 Department of Medicine, The Cancer Institute of New Jersey, UMDNJ- noic acid (CRA) and interferon (IFN) enhanced the effectRWJMS, New Brunswick NJ, USA © 2010 DiPaola et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.DiPaola et al. Journal of Translational Medicine 2010, 8:20 Page 2 of 9http://www.translational-medicine.com/content/8/1/20 disease or a PSA level of ≥ 20 ng/ml. Patients wereof paclitaxel che ...