Ahmann D L, Schaid D J, Bisel H F, Hahn R G, Edmonson J H, Ingle J N
Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905.
J Clin Oncol. 1987 Dec;5(12):1928-32. doi: 10.1200/JCO.1987.5.12.1928.
Since current clinical trials assessing new agents occur in patients with advanced breast cancer having failed one and sometimes many polychemotherapy programs, these new agents may not be given a fair trial. In an effort to assess the possibility of using an alternative study design, we analyzed older clinical trials that used a controlled study design, randomizing between a single new drug and an established polychemotherapy program with a cross-over design upon failure. We were interested in noting that the pooled data did display a slight survival advantage (median 3.7 months) for the group receiving polychemotherapy as initial therapy. The survival distributions were clearly not significant using the log rank test, but did approach significance using the Smirnov. It is apparent that, while some slight advantage does occur for that group of patients receiving initial polychemotherapy, the magnitude of this effect is not great and is short in duration. Serious consideration should be given to the assessment of new agents as first-line therapy, particularly should they have a unique mode of action or lessened morbidities or toxicities.
由于目前评估新药物的临床试验是在晚期乳腺癌患者中进行的，这些患者已经经历了一个且有时是多个多药化疗方案的失败，因此这些新药物可能无法得到公正的试验。为了评估使用替代研究设计的可能性，我们分析了较早期的临床试验，这些试验采用了对照研究设计，在单一新药和既定的多药化疗方案之间进行随机分组，并在失败时采用交叉设计。我们注意到，汇总数据确实显示接受多药化疗作为初始治疗的组有轻微的生存优势（中位生存期3.7个月）。使用对数秩检验，生存分布显然没有显著差异，但使用斯米尔诺夫检验时确实接近显著差异。很明显，虽然接受初始多药化疗的那组患者确实有一些轻微优势，但这种效应的程度不大且持续时间短。应认真考虑将新药物评估为一线治疗，特别是如果它们具有独特的作用模式或更低的发病率或毒性。
