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-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.


METHODS
Patients with a histologically confirmed non-resectable NSCLC, measurable lesion, performance status < or = 3, and informed consent were enrolled. The chemotherapy schedule included cisplatin 60 mg/m2 and mitomycin-c 10 mg/m2 day 1 and vindesine 3 mg/m2 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-c is feasible and shows some activity in the treatment of NSCLC, with manageable toxicity.
ULSS Ospedale Civile, Divisione de Oncologia, Roma, Italy. franre@ermes.it
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D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005234:Fatty Liver / Q000139:chemically induced; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009422:Nervous System Diseases / Q000139:chemically induced; D010865:Pilot Projects; D012074:Remission Induction; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014751:Vindesine / Q000008:administration & dosage / Q000009:adverse effects
D016685:Mitomycin; D015474:Isotretinoin; D002945:Cisplatin; D014751:Vindesine