Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: Effects on survival and quality of life

Purpose: Chemotherapy for non-small-cell lung cancer (NSCLC) remains contro versial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influencer durat ion and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease, Patients and Methods: Ambulatory patients with NSCLC, aged 75 years or youn ger with localized disease, were randomized in MIC1 to receive up to four c ycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and ci splatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + P T) or radiotherapy (RT) alone, Extensive-stage patients were randomized in MIC2 ta identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone, Short-term change in quality of life (QOL) was assessed i n a subgroup of patients. Data from the two trials were combined to allow m ultivariate and stratified survival analyses. Results: Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significa ntly in MIC2), The median survival time in MIC1 was 11.7 months (CT + PT) v ersus 9.7 months (RT alone) (P = .14); whereas in MIC2, median survival tim e was 6.7 months (CT + PC) compared with 4.8 months (PC alone) (P = .03), Q OL, assessed in 134 patients from start of trial to week 6, showed improvem ent with chemotherapy and deterioration with standard treatment, In the com bined analysis of 797 randomized patients, the positive effect of MIC on su rvival was significant overall (P = .01) and after adjusting for prognostic factors (P = .01). Conclusion: MIC chemotherapy prolongs survival in unresectable NSCLC withou t compromising QOL. (C) 1999 by American Society of Clinical Oncology.