Combined Weekly Topotecan and Biweekly Bevacizumab in Women With Platinum-Resistant Ovarian, Peritoneal, or Fallopian Tube Cancer Results of a Phase 2 Study
Combined Weekly Topotecan and Biweekly Bevacizumab in Women With Platinum-Resistant Ovarian, Peritoneal, or Fallopian Tube Cancer Results of a Phase 2 Study
复制标题
DOI：
10.1002/cncr.25967
复制
发表时间：
2011-08-15
期刊：
影响因子：
6.2
通讯作者：
Malpass, Thomas W.
中科院分区：
文献类型：
--
作者：
McGonigle, Kathryn F.;Muntz, Howard G.;Malpass, Thomas W.
背景：进行了一项2期试验，以确定每周一次拓扑替康和双周贝伐单抗联合治疗原发性或继发性铂耐药卵巢癌、腹膜癌或输卵管癌（OC）的毒性和疗效。方法：在28天的周期中，患者在第1天和第15天使用贝伐单抗10 mg/kg，在第1天、第8天和第15天使用拓扑替康4 mg/m(2)，直到疾病进展（PD）或过度毒性。主要终点为无进展生存期（PFS）；次要目标包括总生存期（OS）、客观反应和毒性。结果：患者（N = 40）平均接受8个治疗周期。毒性一般为轻度或中度，中性粒细胞减少（18%）、高血压（20%）、胃肠道毒性（18%）、疼痛（13%）、代谢毒性（15%）、肠梗阻（10%）和心脏毒性（8%）是最常见的3级和4级不良事件。无肠穿孔、发热性中性粒细胞减少或治疗相关死亡发生。中位PFS和OS分别为7.8（95%可信区间[CI]， 3.0-9.4）和16.6个月（95% CI, 12.8-22.9）， 22例（55%）患者无进展（>= 6个月）。10例（25%）患者部分缓解（PR）， 14例（35%）患者病情稳定（SD）， 16例（40%）患者患有PD。先前接受2种方案治疗的患者比接受1种方案治疗的患者获益更大，分别为78.9%和42.9% (P = 0.03)；中位PFS: 10.9个月vs 2.8个月（P = 0.08）；中位生存期22.9个月vs 12.8个月（P = 0.02）。结论：每周一次拓扑替康联合双周贝伐单抗对铂耐药OC患者具有可接受的毒性和令人鼓舞的疗效；值得进一步研究。癌症2011;117:3731-40。(C) 2011年美国癌症协会。
BACKGROUND: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC). METHODS: Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m(2) on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary end-point was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity. RESULTS: Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for >= 6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02). CONCLUSIONS: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted. Cancer 2011;117:3731-40. (C) 2011 American Cancer Society.