A Phase 2 Study of Estramustine, Docetaxel, and Bevacizumab in Men With Castrate-Resistant Prostate Cancer Results From Cancer and Leukemia Group B Study 90006
A Phase 2 Study of Estramustine, Docetaxel, and Bevacizumab in Men With Castrate-Resistant Prostate Cancer Results From Cancer and Leukemia Group B Study 90006
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DOI：
10.1002/cncr.25421
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发表时间：
2011-02-01
期刊：
影响因子：
6.2
通讯作者：
Small, Eric J.
中科院分区：
文献类型：
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作者：
Picus, Joel;Halabi, Susan;Small, Eric J.
背景：多西他赛的使用延长了去势抵抗性前列腺癌（CRPC）患者的生存期。贝伐珠单抗抑制血管内皮生长因子（VEGF）可能会进一步增强多西他赛和雌莫司汀在CRPC患者中的抗肿瘤作用。方法：本合作组试验招募CRPC男性患者。患者在每个周期的第1天至第5天接受口服雌莫司汀280 mg每日3次，第2天接受多西他赛70 mg/m2和贝伐珠单抗15 mg/kg，每3周一次。每个周期监测前列腺特异性抗原（PSA）值，每3个周期进行一次影像学检查。主要终点是无进展生存期（PFS），次要目标是安全性、PSA下降、可测量的疾病缓解和总生存期。结果：79例患者入组; 77例患者接受了中位数为8个周期的治疗，可评价。在58例患者（75%）中观察到PSA下降50%。39例有可测量疾病的患者中有23例有部分缓解（59%）。中位PFS为8个月，总中位生存期为24个月。中性粒细胞减少无发热（69%）、疲乏（25%）和血栓形成/栓塞（9%）是最常见的重度毒性。77例患者中有24例因疾病进展而退出方案治疗，77例患者中有35例因医生或患者决定而退出，15例患者因继发性毒性而退出。结论：多西他赛、雌莫司汀和贝伐单抗联合用药是可以耐受的，但会出现毒性。尽管PFS终点未达到预期水平，但观察到令人鼓舞的抗肿瘤活性和总生存期。正在进行贝伐珠单抗在CRPC中作用的进一步III期评价。Cancer 2011;117：526-33. (C)2010年美国癌症协会
BACKGROUND: The use of docetaxel prolongs survival for patients with castrate-resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the antitumor effect of docetaxel and estramustine in patients with CRPC. METHODS: This cooperative group trial enrolled men with CRPC. Patients received oral estramustine 280 mg 3 times daily on Days 1 through 5 of every cycle plus 70 mg/m(2) docetaxel and 15 mg/kg bevacizumab on Day 2 every 3 weeks. Prostate-specific antigen (PSA) values were monitored every cycle, and imaging studies were obtained every 3 cycles. The primary endpoint was progression-free survival (PFS), and the secondary objectives were safety, PSA decline, measurable disease response, and overall survival. RESULTS: Seventy-nine patients were enrolled; and 77 patients received a median of 8 cycles and were evaluable. A 50% PSA decline was observed in 58 patients (75%). Twenty-three of 39 patients with measurable disease had a partial response (59%). The median PFS was 8 months, and the overall median survival was 24 months. Neutropenia without fever (69%), fatigue (25%), and thrombosis/emboli (9%) were the most common severe toxicities. Twenty-four of 77 patients were removed from protocol treatment because of disease progression, 35 of 77 patients were removed because of a physician or patient decision, and 15 patients were removed secondary to toxicity. CONCLUSIONS: The combination of docetaxel, estramustine, and bevacizumab was tolerable but complicated by toxicity. Although the endpoint of PFS did not meet the desired level, encouraging antitumor activity and overall survival were observed. Further phase 3 evaluation of the role of bevacizumab in CRPC is ongoing. Cancer 2011;117:526-33. (C) 2010 American Cancer Society