Cisplatin, vindesine, mitomycin-c and 13-cis retinoic acid in the treatment of advanced non-small cell lung cancer. A phase II pilot study. Anticancer Res. 20:1985-90, 2000.

Background: Thirteen-cis retinoic acid (RA) has been shown to have growth-inhibitory and differentiative activity on non-small cell lung cancer (NSCLC) cells in vitro. This promoted the rationale for combining RA with three active drugs, cisplatin (CDDP) vindesine (VDS) and mitomycin-c (MMC) in the treatment of advanced NSCLC. Patients and methods: Patients with a histologically confirmed non-resectable NSCLC, mensurable lesion, performance status less than or equal to 3, and informed consent were enrolled. The chemotherapy schedule included cisplatin 60 mg/m(2) and mitomycin-c 10 mg/m(2) day 1 and vindesine 3 mg/m(2) on days 1 and 5, every 4 weeks. RA was administered orally, at a dose of 0.5 mg/kg, 5 days per week, during chemotherapeutic intervals and to responding patients until disease progression was observed. Results: Thirty patients, receiving a total of 163 chemotherapy courses, were evaluated for response and toxicity. Objective responses included complete response in 2 patients (7%), partial response in 10 patients (33%), stable disease in 9 patients (30%) and progressive disease in 9 patients (30%), (response rate 40%: Confidence interval 95% 22.7% to 59.4%). Median time to progression was 8.6 months (range 3.9-45+). Median overall survival was 11.3 months (range 1-45+). The 1-year survival rate was 47%. Toxicity (WHO) included nausea and vomiting grade 2 in 6 patients, transient ileus in 3 patients and grade 3-4 leukopenia in 5 patients. Two patients underwent surgical resection of residual disease and remain in CR. Conclusions: The addition of RA to cisplatin, vindesine and mitomycin-e is feasible and shows some activity in the treatment of NSCLC, with manageable toxicity.