Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup
Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup
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DOI：
10.1200/jco.2008.19.1684
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发表时间：
2009-03-20
影响因子：
45.3
通讯作者：
Roth, Lawrence M.
中科院分区：
文献类型：
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作者：
Bookman, Michael A.;Brady, Mark F.;Roth, Lawrence M.
为了确定是否掺入额外的细胞毒性剂改善接受卡铂和紫杉醇治疗的晚期上皮性卵巢癌（EOC）和原发性腹膜癌妇女的总生存期（OS）和无进展生存期（PFS）。并打算进行间隔细胞减少，然后随机分配到5组，与卡铂和紫杉醇相比，合并吉西他滨，甲氧基聚乙烯糖基化脂质体阿霉素或拓扑替康。主要终点是OS，并确定成对比较的参考臂，有90%的机会检测到一个真正的危险比为1.33，限制I型错误为5%（双尾）的四个comparation.ResultsAccrual超过1,200例患者每年。在参考组发生272起事件后进行了事件触发的中期分析，研究结束时招募了4，312名女性。两组在人口统计学和预后因素方面平衡良好，79%的患者完成了8个周期的治疗。任何实验方案均未改善PFS或OS。生存分析组的残留疾病的大小定义也未能显示实验的好处在任何subgroup.ConclusionCompared与标准紫杉醇和卡铂，除了第三个细胞毒性药物提供无进展生存率或OS后，最佳或次优cytoreduction。双阶段、多组、III期临床试验可以有效地评估多种实验方案与单一参考组的对比，需要开发手术和传统铂类化疗以外的新干预措施，以进一步改善晚期EOC女性患者的结局。
PurposeTo determine if incorporation of an additional cytotoxic agent improves overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma who receive carboplatin and paclitaxel.Patients and MethodsWomen with stages III to IV disease were stratified by coordinating center, maximal diameter of residual tumor, and intent for interval cytoreduction and were then randomly assigned among five arms that incorporated gemcitabine, methoxypolyethylene glycosylated liposomal doxorubicin, or topotecan compared with carboplatin and paclitaxel. The primary end point was OS and was determined by pairwise comparison to the reference arm, with a 90% chance of detecting a true hazard ratio of 1.33 that limited type I error to 5% (two-tail) for the four comparisons.ResultsAccrual exceeded 1,200 patients per year. An event-triggered interim analysis occurred after 272 events on the reference arm, and the study closed with 4,312 women enrolled. Arms were well balanced for demographic and prognostic factors, and 79% of patients completed eight cycles of therapy. There were no improvements in either PFS or OS associated with any experimental regimen. Survival analyses of groups defined by size of residual disease also failed to show experimental benefit in any subgroup.ConclusionCompared with standard paclitaxel and carboplatin, addition of a third cytotoxic agent provided no benefit in PFS or OS after optimal or suboptimal cytoreduction. Dual-stage, multiarm, phase III trials can efficiently evaluate multiple experimental regimens against a single reference arm. The development of new interventions beyond surgery and conventional platinum-based chemotherapy is required to additionally improve outcomes for women with advanced EOC.