沙利度胺联合拓扑替康与单用拓扑替康治疗复发性上皮性卵巢癌女性的前瞻性随机试验。

A prospective randomized trial of thalidomide with topotecan compared with topotecan alone in women with recurrent epithelial ovarian carcinoma.

作者信息

Downs Levi S, Judson Patricia L, Argenta Peter A, Ghebre Rahel, Geller Melissa A, Bliss Robin L, Boente Matthew P, Nahhas William A, Abu-Ghazaleh Samir Z, Chen M Dwight, Carson Linda F

机构信息

Division of Gynecologic Oncology, University of Minnesota, Minneapolis, Minnesota 55455, USA.

出版信息

Cancer. 2008 Jan 15;112(2):331-9. doi: 10.1002/cncr.23164.

DOI:10.1002/cncr.23164

PMID:18058810

Abstract

BACKGROUND

Thalidomide is an antiangiogenic agent with immune modulating potential. The objective of this study was to determine response rates among women who were treated for recurrent ovarian cancer using topotecan with or without thalidomide.

METHODS

Women were enrolled in this multicenter, prospective, randomized phase 2 trial between April 2001 and July 2005. Eligible patients had recurrent epithelial ovarian carcinoma with measurable disease or elevated CA 125 values. Patients had received prior platinum-based chemotherapy. Treatment arms received topotecan at a dose of 1.25 mg/m(2) on Days 1 through 5 of a 21-day cycle with or without thalidomide starting at a dose of 200 mg per day and then increasing the dose as tolerated. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria. The chi-square test was used to assess differences in response and toxicity, and the log-rank test was used to compare Kaplan-Meier survival curves.

RESULTS

The analysis included 69 women (39 women in the control arm and 30 women in the thalidomide arm). Known prognostic factors, including platinum sensitivity, were represented equally in each arm. The median thalidomide dose was 200 mg per day. The overall response rate in the control arm was 21% (complete response [CR] rate, 18%; partial response [PR] rate, 3%) compared with 47% in the thalidomide arm (CR rate, 30%; PR rate, 17%) (P= .03). The median progression-free survival for the control arm was 4 months compared with 6 months in the thalidomide arm (P= .02). The median overall survival was 15 months in the control arm and 19 months in the thalidomide arm (P= .67). Toxicities were similar between groups.

CONCLUSIONS

The addition of thalidomide to topotecan for the treatment of recurrent ovarian cancer appears to improve response rates, and the authors believe that it warrants study through larger phase 3 trials.

摘要

背景

沙利度胺是一种具有免疫调节潜力的抗血管生成药物。本研究的目的是确定使用拓扑替康联合或不联合沙利度胺治疗复发性卵巢癌的女性患者的缓解率。

方法

2001年4月至2005年7月期间，女性患者被纳入这项多中心、前瞻性、随机2期试验。符合条件的患者患有复发性上皮性卵巢癌，伴有可测量的疾病或CA 125值升高。患者此前接受过铂类化疗。治疗组在21天周期的第1至5天接受剂量为1.25mg/m²的拓扑替康治疗，联合或不联合沙利度胺，沙利度胺起始剂量为每日200mg，然后根据耐受情况增加剂量。毒性根据美国国立癌症研究所通用毒性标准进行分级。采用卡方检验评估缓解率和毒性的差异，采用对数秩检验比较Kaplan-Meier生存曲线。

结果

分析纳入了69名女性（对照组39名女性，沙利度胺组30名女性）。已知的预后因素，包括铂敏感性，在每组中分布均衡。沙利度胺的中位剂量为每日200mg。对照组的总缓解率为21%（完全缓解[CR]率为18%；部分缓解[PR]率为3%），而沙利度胺组为47%（CR率为30%；PR率为17%）（P = 0.03）。对照组的中位无进展生存期为4个月，沙利度胺组为6个月（P = 0.02）。对照组的中位总生存期为15个月，沙利度胺组为19个月（P = 0.67）。两组之间的毒性相似。