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 > or = four cycles 
of therapy had > or = 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.