Effect of amifostine on toxicities associated with sequential chemotherapy and radiation therapy for unresectable non-small-cell lung cancer: Results of a phase II trial

Purpose: To determine the effect of amifostine on the safety and efficacy of induction chemotherapy with high-dose cisplatin and vinblastine followed by large-field thoracic irradiation to 60 Gy in patients with stage IIIA or IIIB non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-six patients with unresectable stage IIIA or IIIB NSCLC were entered onto the study between May 1991 and November 1994. Patients received amifostine (740 or 910 mg/m²) followed by cisplatin (120 mg/m²) on days 1 and 29. Vinblastine (5 mg/ m²) was given weekly for 5 weeks with no amifostine pretreatment. Following chemotherapy, patients received amifostine (340 mg/m² 4 days a week for 5 weeks, or 200 mg/m² 5 days a week for 6 weeks) 15 minutes before definitive thoracic radiation therapy to a total dose of 60 Gy in 6 weeks. Results: Twenty-five patients were assessable far response and survival. The objective response rate was 60%. One-, 2-, and 3- year survival rates were 55%, 23%, and 23%. There was no grade 3 or greater renal toxicity during chemotherapy or grade 3 or greater esophagitis during radiation therapy. Neutropenia (secondary to vinblastine use) was the only grade 4 toxicity. There were no treatment-related deaths. Conclusion: Amifostine can be administered safely wit high-dose cisplatin, vinblastine, and radiation therapy for NSCLC. The response rate and survival data provide no evidence that amifostine impairs response to treatment. Amifostine appears to reduce cisplatin-related nephrotoxicity and radiation-induced esophagitis.