Combination chemotherapy with cytotoxic agents is the regular treatment for patients with advanced non-small cell lung cancer (NSCLC), good performance status, and no major clinical contraindications. Since the early 1980s, platinum-based chemotherapy is the cornerstone of this treatment, while combinations containing long-acting alkylating agents have been nearly abandoned, and represent a sort of historical treatment. Nevertheless, the real survival benefits of cisplatin are uncertain and still debated. To attempt an answer, the Cuneo Lung Cancer Study Group (CuLCaSG) carried out a clinical trial comparing a platinum (MVP) versus a non-platinum-based combination chemotherapy (MACC). The study comprised 156 patients with advanced NSCLC randomly assigned to the two treatment arms. MACC and MVP chemotherapies were given as originally described and continued until progression of disease, unacceptable toxicity, or refusal by the patient. For a median of four cycles of MVP and three cycles of MACC, the median dose intensity (DI) reached was, respectively, 95% and 100% of the intended (P = 0.0132). In all, 27 objective responses (1 complete and 16 partial responses in patients allocated to MVP versus 10 partial responses of the MACC group) were observed. Median progression-free and global survivals were, respectively, 21 and 34 weeks for MVP and 20 and 31 weeks for MACC (non-significant differences). The treatment plan was found non-significant also in multivariate analysis of survival. Toxicity was rather similar in the two arms, except for more severe neurological toxicity, anemia, thrombocytopenia, nausea, and vomiting in patients on MVP. Alopecia was more common after MACC. Subjective tolerance to treatment, and perception of physical and psychological well-being were rated similarly by patients of both groups. In conclusion, MVP was moderately more active than MACC, and showed a foreseeable and reversible toxicity of a low-medium grade. However, this CuLCaSG study failed to substantiate any survival benefit from the use of platinum in combination with other cytotoxic agents. (C) 1997 Elsevier Science Ireland Ltd.