title: Response to chemotherapy has predictive value for further survival of patients with advanced non-small cell lung cancer: 10 years experience of the European Lung Cancer Working Party.
abstract: 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.
authors.affiliation: Unité de Biostatistique, Institut Jules Bordet, Bruxelles, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Paesmans
authors.forename: J P
authors.initials: JP
authors.lastname: Sculier
authors.forename: P
authors.initials: P
authors.lastname: Libert
authors.forename: G
authors.initials: G
authors.lastname: Bureau
authors.forename: G
authors.initials: G
authors.lastname: Dabouis
authors.forename: J
authors.initials: J
authors.lastname: Thiriaux
authors.forename: J
authors.initials: J
authors.lastname: Michel
authors.forename: O
authors.initials: O
authors.lastname: Van Cutsem
authors.forename: R
authors.initials: R
authors.lastname: Sergysels
authors.forename: P
authors.initials: P
authors.lastname: Mommen
authors.forename: J
authors.initials: J
authors.lastname: Klastersky
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D005544:Forecasting; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D002945:Cisplatin