A COMPARISON OF CARBOPLATIN PLUS METHOTREXATE VERSUS METHOTREXATE ALONE IN PATIENTS WITH RECURRENT AND METASTATIC HEAD AND NECK-CANCER
A COMPARISON OF CARBOPLATIN PLUS METHOTREXATE VERSUS METHOTREXATE ALONE IN PATIENTS WITH RECURRENT AND METASTATIC HEAD AND NECK-CANCER
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DOI：
10.1200/jco.1989.7.9.1341
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发表时间：
1989-09-01
影响因子：
45.3
通讯作者：
AISNER, J
中科院分区：
文献类型：
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作者：
EISENBERGER, M;KRASNOW, S;AISNER, J
复发性和转移性头颈部鳞状细胞癌（SCCHN）患者根据体力状态、疾病程度和既往放疗进行分层，随后随机接受卡铂治疗（CBDCA; Bristol-Myers，Wallingford，CT）每月静脉内（IV）施用，最初以400 mg/m2的剂量与每周以40 mg/m2的剂量IV给予的甲氨蝶呤（MTX）组合，或以相同的剂量/时间表单独给予MTX。显著的剂量限制性骨髓抑制需要将CBDCA剂量降低至300 mg/m2，随后降低至200 mg/m2。非血液学毒性不显著。我们的研究目的是确定CBDCA加MTX是否比单药MTX在应答率方面产生实质性改善。CBDCA + MTX的缓解率为50%（完全[CR]加部分缓解[PR]），而MTX为25%，被指定为待检测的差异。我们采用两阶段随机试验设计，允许提前终止涉及相对无效治疗方案的研究。采用这种设计，如果CBDCA + MTX的应答者数量不上级于MTX，则研究可在第一阶段（每个治疗组入组20例患者）后关闭。每组20例患者中有5例对治疗有反应，我们能够得出结论，在这组患者中，与单独使用MTX相比，在MTX中添加CBDCA不太可能导致反应率增加两倍。这种两阶段设计代表了一种简单而有效的方法，用于测试含有至少一种活性剂的新组合相对于该疾病中合适的对照组的相对功效。它解决了用相对无效的治疗方法继续进行试验的科学和伦理问题，同时提供了一种可靠的方法，用于确定可能代表重大治疗进展的非常有效的方案。
Patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) were stratified by performance status, extent of disease, and prior radiotherapy and subsequently randomized to receive carboplatin (CBDCA; Bristol-Myers, Wallingford, CT) administered intravenously (IV) monthly, initially at doses of 400 mg/m2 in combination with methotrexate (MTX) given IV weekly at doses of 40 mg/m2 or MTX alone at the same dose/schedule. Significant dose-limiting myelosuppression required CBDCA dose reductions to 300 mg/m2 and, subsequently, 200 mg/m2. Nonhematological toxicities were not significant. Our study objective was to determine whether CBDCA plus MTX produce a substantial improvement in response rate over single-agent MTX. A response rate of 50% (complete [CR] plus partial response [PR]) for CBDCA plus MTX compared with 25% for MTX was specified as the difference to be detected. We employed a two-stage study design for randomized trials that allowed for early termination of studies involving relatively ineffective treatment regimens. With this design, the study could be closed after the first stage (20 patients entered onto each treatment arm) if the number of responders to CBDCA plus MTX were not superior to MTX. Five of 20 patients responded to treatment in each arm, and we were able to conclude that the addition of CBDCA to MTX is unlikely to result in a twofold increase in response rate compared with MTX alone in this group of patients. This two-stage design represents a simple and efficient method of testing the relative efficacy of new combinations containing at least one active agent against a suitable control arm in this disease. It addresses scientific and ethical issues of continuing testing with relatively ineffective treatments, and at the same time provides a reliable method for identifying very active regimens likely to represent significant therapeutic advances.