High-dose cisplatin and vinblastine plus amifostine for metastatic non- small cell lung cancer

Amifostine is a sulfhydryl compound that protects against the cytotoxicity of cytotoxic agents and ionizing radiation. Preclinical and clinical studies also suggest that amifostine may potentiate the effects of cytotoxic drugs. We therefore conducted a phase II trial of amifostine, cisplatin, and vinblastine in 25 previously untreated patients with metastatic non-small cell lung cancer. Patients received amifostine (740 or 910 mg/m²) prior to cisplatin 120 mg/m² on day 1, plus vinblastine 5 mg/m² weekly. Cycles were repeated every 4 weeks. Patients were required to have good performance status, no prior chemotherapy or biologic therapy, adequate organ function, and measurable disease. Sixteen of 25 evaluable patients had an objective response (64%; 95% confidence interval, 45% to 85%). With a median duration of follow-up of 19.2 months, the estimated median length of survival is 17 months and the 1-year survival rate is 64% (+10%). Toxicities included reversible grade 3 nephrotoxicity (12%), hypotension (16%), grades 3 and 4 neutropenia (8% and 92%, respectively), and nausea and vomiting (32% and 4%, respectively). Grade 3 neuropathy was observed in seven patients at cumulative cisplatin doses ranging between 324 and 660 mg/m²; grade 3 ototoxicity occurred in three patients at cumulative cisplatin doses ranging between 390 and 450 mg/m². The amifostine, cisplatin, and vinblastine regimen appears to be highly active against metastatic non-small cell lung cancer. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative cisplatin doses. Additional studies are warranted to confirm the high response rate and prolonged survival, and to determine the mechanism of the antitumor effect.