Chemotherapy of advanced non-small-cell lung cancer: A comparison of three active regimens. A randomized trial of the Italian Oncology Group for Clinical Research (G.O.I.R.C.)

Background: Cisplatin-based chemotherapy is generally considered the most active treatment for advanced non-small-cell lung cancer. The combination of cisplatin and etoposide had for some time been the standard treatment at our center. Of the other active regimens, cisplatin in combination with mitomycin-C, vindesine or ifosfamide (MVP or MIC) showed the highest response rates. We decided to perform a comparative trial of the three «best» regimens in order to define a possible standard regimen in advanced NSCLC. Materials and methods: From May 1989 to April 1992, 393 consecutive, previously untreated NSCLC patients, stages IIIB and IV, were randomized to receive either cisplatin (120 mg/sqm day 1)+etoposide (100 mg/sqm days 1-3) every 3 weeks (PE) or cisplatin (120 mg/sqm every 4 weeks) + mitomycin-C (8 mg/sqm days 1-29-71) + vindesine (3 mg/sqm days 1-8-15-22) (MVP) or cisplatin (120 mg/sqm day 1) + mitomycin-C (6 mg/sqm day 1) + ifosfamide (3 mg/ sqm day 2) every 3 weeks (MIC). Of these, 382 were evaluable for survival and 360 for response. Results: Response rates were statistically higher for both MIC (40%) and MVP (36%) than for the PE arm (23%). Survival estimates analyzed by the log-rank test showed a significant benefit (p < 0.04) for patients treated with three-drug regimens (MVP; MIC) as compared to those in the PE arm. The main toxicity was myelosuppression; thrombocytopenia WHO grade 3-4 was worse in the MIC arm; nephrotoxicity grade 3-4 was also more frequent in the MIC arm. Conclusions: A three-drug cisplatin-based regimen (MVP; MIC) should be considered as reference treatment in NSCLC