RESPONSE TO CHEMOTHERAPY HAS PREDICTIVE VALUE FOR FURTHER SURVIVAL OFPATIENTS WITH ADVANCED NONSMALL CELL LUNG-CANCER - 10 YEARS EXPERIENCE OF THE EUROPEAN LUNG-CANCER WORKING PARTY

The aim of this study was the assessment of the predictive value for s urvival of an antitumoral response to three courses of chemotherapy in association with various pretreatment characteristics in patients wit h non-resectable non-small cell lung cancer treated by cisplatin-(or c arboplatin)-based combination regimens. Patients considered for this s tudy were eligible patients with advanced non-small cell lung cancer r egistered in one of the seven trials conducted by the European Lung Ca ncer 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 we re assessed in this analysis. Data were prospectively collected on 23 pretherapeutic variables and objective response after three chemothera py cycles. The predictive value of response to chemotherapy on surviva l (measured from the time of response assessment i.e. 12 weeks after r egistration in the trial) was studied by univariate analysis as well a s by multivariate methods (adjustment of the impact of several covaria tes 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% con fidence interval of 22-25 weeks. By univariate analysis, we identified an objective response to chemotherapy as a highly significant discrim inant marker (P<0.0001) for further survival with estimated median sur vival 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 procedur e, this variable was the first selected explanatory variable. Its effe ct was adjusted by the introduction in the model of initial disease ex tent, Karnofsky performance status, serum calcium level and white bloo d cell count. These results were consistent with those obtained by app lication 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 consis tent 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 classificati on of the patients into three subgroups which needs to be validated in other series. (C) 1997 Elsevier Science Ltd.