Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer: A report of high response rates and prolonged survival

Purpose: Based on preclinical and clinical studies that suggested amifostine may potentiate the effects of cytotoxic drugs, we conducted a phase II trial of amifostine, cisplatin, and vinblastine (ACV) in patients with metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-five patients with metastatic NSCLC received amifostine (740 or 910 mg/m²) before 120 mg/m² of cisplatin on day 1, plus weekly 5 mg/m² of vinblastine without amifostine. 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. Results: Sixteen of 25 assessable patients had an objective response documented by computed tomographic (CT) scan (64%; 95% confidence interval, 45% to 85%). With a median duration of follow-up of 19.2 months, the estimated median survival is 17 months and 1-year survival is 64% (± 10%). Toxicities included grades 3 and 4 neutropenia (8% and 92%, respectively) and nausea and vomiting (32% and 4%, respectively). Reversible grade 3 nephrotoxicity occurred in 12% of patients, although only one of 13 patients (7%) who received ≥ four cycles of therapy had ≥ 40% reduction in creatinine clearance. Grade 3 neuropathy was observed in seven patients at cumulative cisplatin doses that ranged from 324 to 660 mg/m²; grade 3 ototoxicity occurred in three patients at cumulative cisplatin doses that ranged from 390 to 450 mg/m². Four patients (16%) required early stopping of an amifostine infusion due to hypotension. Conclusion: ACV appears to be a highly active regimen in metastatic NSCLC. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative doses of cisplatin. Although the sample size of this trial is small, the results are significantly encouraging to warrant confirmation in randomized multiinstitutional trials.