Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas
Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas
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DOI：
10.1200/jco.2006.10.4117
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发表时间：
2007-07-01
影响因子：
45.3
通讯作者：
Hensley, Martee L.
中科院分区：
文献类型：
--
作者：
Maki, Robert G.;Wathen, J. Kyle;Hensley, Martee L.
目的吉西他滨单药以及吉西他滨与多西他赛联合用药对转移性软组织肉瘤患者具有活性。为了确定在吉西他滨中添加多西他滨是否可以改善转移性软组织肉瘤患者的临床结果，我们比较了吉西他滨的固定剂量率输注与较低剂量的吉西他滨与多西他赛的输注。 患者和方法在这项开放标签 II 期临床试验中，主要终点是肿瘤反应，定义为完全或部分反应或持续至少 24 周的疾病稳定。贝叶斯自适应随机化程序用于产生有利于更优治疗的随机化不平衡，并考虑到治疗与亚组的相互作用。结果 122 名随机分配的患者中，有 119 名患者的结果可评估。适应性随机化将 73 名患者 (60%) 分配给吉西他滨-多西他赛组，49 名患者 (40%) 分配给单独吉西他滨组，表明吉西他滨-多西他赛组效果更好。实体瘤缓解率的客观缓解评估标准为 16%（吉西他滨-多西他赛）和 8%（吉西他滨）。根据这些数据，吉西他滨-多西紫杉醇在无进展生存和总生存方面优于后验概率分别为 0.98 和 0.97。吉西他滨联合多西他赛的中位无进展生存期为 6.2 个月，单用吉西他滨为 3.0 个月；吉西他滨-多西他赛的中位总生存期为 17.9 个月，吉西他滨的中位总生存期为 11.5 个月。与单独使用吉西他滨相比，接受吉西他滨-多西他赛治疗的患者因毒性而停药的后验概率为 0.999。结论 与单独使用吉西他滨相比，吉西他滨-多西他赛的无进展生存期和总生存期均优于单独使用吉西他滨，但毒性增加。适应性随机化是减少接受较差治疗的患者数量的有效方法。
PurposeGemcitabine as a single agent and the combination of gemcitabine and docetaxel have activity in patients with metastatic soft tissue sarcoma. To determine if the addition of docetaxel to gemcitabine improved clinical outcome of patients with metastatic soft tissue sarcomas, we compared a fixed dose rate infusion of gemcitabine versus a lower dose of gemcitabine with docetaxel.Patients and MethodsIn this open-label phase II clinical trial, the primary end point was tumor response, defined as complete or partial response or stable disease lasting at least 24 weeks. A Bayesian adaptive randomization procedure was used to produce an imbalance in the randomization in favor of the superior treatment, accounting for treatment-subgroup interactions.ResultsOne hundred nineteen of 122 randomly assigned patients had assessable outcomes. The adaptive randomization assigned 73 patients (60%) to gemcitabine-docetaxel and 49 patients (40%) to gemcitabine alone, indicating gemcitabine-docetaxel was superior. The objective Response Evaluation Criteria in Solid Tumors response rates were 16% (gemcitabine-docetaxel) and 8% (gemcitabine). Given the data, the posterior probabilities that gemcitabine-docetaxel was superior for progression-free and overall survival were 0.98 and 0.97, respectively. Median progression-free survival was 6.2 months for gemcitabine-docetaxel and 3.0 months for gemcitabine alone; median overall survival was 17.9 months for gemcitabine-docetaxel and 11.5 months for gemcitabine. The posterior probability that patients receiving gemcitabine-docetaxel had a shorter time to discontinuation for toxicity compared with gemcitabine alone was .999.ConclusionGemcitabine-docetaxel yielded superior progression-free and overall survival to gemcitabine alone, but with increased toxicity. Adaptive randomization is an effective method to reduce the number of patients receiving inferior therapy.