Cisplatin, vindesine, mitomycin-C and 13-cis retinoic acid in the treatment of advanced non small cell lung cancer. A phase II pilot study

Background: Thirteen-cis retinoic acid (RA) has been shown to have growth-i nhibitory and differentiative activity on non-small cell lung cancer (NSCLC ) cells in vitro. This promoted the rationale for combining RA with three a ctive drugs, cisplatin (CDDP) vindesine (VDS) and mitomycin-c (MMC) in the treatment of advanced NSCLC. Patients and methods: Patients with a histolog ically confirmed non-resectable NSCLC, mensurable lesion, performance statu s less than or equal to 3, and informed consent were enrolled. The chemothe rapy 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 administer ed orally, at a dose of 0.5 mg/kg, 5 days per week, during chemotherapeutic intervals and to responding patients until disease progression was observe d. Results: Thirty patients, receiving a total of 163 chemotherapy courses, were evaluated for response and toxicity. Objective responses included com plete response in 2 patients (7%), partial response in 10 patients (33%), s table disease in 9 patients (30%) and progressive disease in 9 patients (30 %), (response rate 40%: Confidence interval 95% 22.7% to 59.4%). Median tim e to progression was 8.6 months (range 3.9-45+). Median overall survival wa s 11.3 months (range 1-45+). The 1-year survival rate was 47%. Toxicity (WH O) 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 su rgical resection of residual disease and remain in CR. Conclusions: The add ition of RA to cisplatin, vindesine and mitomycin-e is feasible and shows s ome activity in the treatment of NSCLC, with manageable toxicity.