Amifostine plus cisplatin plus vinorelbine in the treatment of advanced non small cell lung cancer: a multicenter phase II study

Purpose: to evaluate the activity and toxicity of the combination cisplatin plus vinorelbine plus amifostine in advanced non small cell lung cancer (N SCLC). Patients ann methods: a two-stage Simon design was applied. To proce ed after the first stage, responses from seven of 19 patients were needed. Overall, 17 responses from 40 treated patients were required to comply with the design parameter. Inclusion criteria were cyto-histologically proven s tage IIIB-IV NSCLC, age of 70 years or less; Eastern Cooperative Oncology G roup (ECOG) performance status of 2 or less; normal cardiac, hepatic, renal and bone marrow functions; and no previous chemotherapy. Patients were sta ged by physical examination, biochemistry, chest radiograph, brain, thoraci c and abdominal computed tomographic (CT) scans, and bone scan. All patient s received cisplatin 100 mg/m(2) intravenously (iv) day 1, vinorelbine 25 m g/m(2) iv days 1-8-15-22, amifostine 740 mg/m(2) iv day 1 every 4 weeks up to six cycles. Eleven of 40 enrolled patients were stage IIIB and 29 stage IV, with a median age of 57 years (range, 38-70 years). Results: all patien ts were evaluable for response and toxicity (intention to treat analysis). We observed 20 (50%) objective responses, with four (10%) complete response s. Median time to progression was 20 weeks. and median survival was 45 week s. The: toxicity was manageable. The reported main toxicities were neutrope nia grade 4 in 10% of patients, grade 1 and grade 3 nephrotoxicity both in 5% of patients and grade 1 amifostine-related hypotension in 15% of patient s. Conclusion: these data show that cisplatin plus vinorelbine plus amifost ine is an active and feaseable regimen in stage IIIB-IV NSCLC. A phase III trial comparing cisplatin plus vinorelbine versus cisplatin plus vinorelbin e plus amifostine in advanced NSCLC is warranted. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.