Paesmans M, Sculier J P, Libert P, Bureau G, Dabouis G, Thiriaux J, Michel J, Van Cutsem O, Sergysels R, Mommen P, Klastersky J
Unité de Biostatistique, Institut Jules Bordet, Bruxelles, Belgium.
Eur J Cancer. 1997 Dec;33(14):2326-32. doi: 10.1016/s0959-8049(97)00325-0.
The aim of this study was the assessment of the predictive value for survival of an antitumoral response to three courses of chemotherapy in association with various pretreatment characteristics in patients with non-resectable non-small cell lung cancer treated by cisplatin- (or carboplatin)-based combination regimens. Patients considered for this study were eligible patients with advanced non-small cell lung cancer registered in one of the seven trials conducted by the European Lung Cancer Working Party from December 1980 to August 1991. All these trials tested chemotherapy regimens with platinum derivatives (cisplatin and/or carboplatin). In this population of 1052 eligible patients, 752 were assessed in this analysis. Data were prospectively collected on 23 pretherapeutic variables and objective response after three chemotherapy cycles. The predictive value of response to chemotherapy on survival (measured from the time of response assessment i.e. 12 weeks after registration in the trial) was studied by univariate analysis as well as by multivariate methods (adjustment of the impact of several covariates simultaneously on the dependent variable) with adjustment for the pretreatment prognostic variables. After three cycles of chemotherapy, the global estimated median survival time was 24 weeks with a 95% confidence interval of 22-25 weeks. By univariate analysis, we identified an objective response to chemotherapy as a highly significant discriminant marker (P < 0.0001) for further survival with estimated median survival times of 41 weeks (95% CI: 38-46) and 19 weeks (95% CI: 17-20), respectively, for the responding and non-responding patients. In a Cox regression model fitted to the data using a forward stepwise procedure, this variable was the first selected explanatory variable. Its effect was adjusted by the introduction in the model of initial disease extent, Karnofsky performance status, serum calcium level and white blood cell count. These results were consistent with those obtained by application of recursive partitioning and amalgamation algorithms (RECPAM) which led to a classification of the patients into three homogeneous subgroups. Our results, using a classical Cox regression model consistent with those highlighted by application of a RECPAM analysis, found an objective response to chemotherapy to be a predominant predictive factor for further survival, although it did not allow any conclusion about a causal relationship. The RECPAM results led to a classification of the patients into three subgroups which needs to be validated in other series.
本研究旨在评估对于接受以顺铂（或卡铂）为基础的联合化疗方案治疗的不可切除非小细胞肺癌患者，三个疗程化疗的抗肿瘤反应与各种预处理特征对生存的预测价值。本研究纳入的患者为1980年12月至1991年8月期间欧洲肺癌工作组开展的七项试验之一中登记的晚期非小细胞肺癌合格患者。所有这些试验均测试了含铂类衍生物（顺铂和/或卡铂）的化疗方案。在这1052名合格患者中，752名患者纳入了本分析。前瞻性收集了23个治疗前变量和三个化疗周期后的客观反应数据。通过单因素分析以及多变量方法（同时调整几个协变量对因变量的影响）并对预处理预后变量进行调整，研究了化疗反应对生存（从反应评估时间即试验登记后12周开始测量）的预测价值。三个化疗周期后，总体估计中位生存时间为24周，95%置信区间为22 - 25周。通过单因素分析，我们确定化疗的客观反应是进一步生存的高度显著判别标志物（P < 0.0001），反应组和无反应组患者的估计中位生存时间分别为41周（95% CI：38 - 46）和19周（95% CI：17 - 20）。在使用向前逐步法对数据拟合的Cox回归模型中，该变量是首先被选中的解释变量。通过在模型中引入初始疾病范围、卡诺夫斯基体能状态、血清钙水平和白细胞计数来调整其效应。这些结果与应用递归分割和合并算法（RECPAM）获得的结果一致，该算法将患者分为三个同质亚组。我们的结果使用与RECPAM分析突出显示的结果一致的经典Cox回归模型，发现化疗的客观反应是进一步生存的主要预测因素，尽管它未得出任何关于因果关系的结论。RECPAM结果将患者分为三个亚组，这需要在其他系列中进行验证。
