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 effic acy of induction chemotherapy with high-dose cisplatin and vinblastine followed by large-field thoracic irradiation to 60 Gy in patients wit h stage IIIA or IIIB non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-six patients with unresectable stage IIIA or IIIB NSCL C were entered onto the study between May 1991 and November 1994. Pati ents received amifostine (740 or 910 mg/m(2)) followed by cisplatin (1 20 mg/m(2)) on days 1 and 29. Vinblastine (5 mg/m(2)) was given weekly for 5 weeks with no amifostine pretreatment. Following chemotherapy, patients received amifostine (340 mg/m(2) 4 days a week for 5 weeks, o r 200 mg/m(2) 5 days a week for 6 weeks) 15 minutes before definitive thoracic radiation therapy to a total dose of 60 Gy in 6 weeks. Result s: Twenty-five patients were assessable for 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 radiatio n therapy. Neutropenia (secondary to vinblastine use) was the only gra de 4 toxicity, There were no treatment-related deaths. Conclusion: Ami fostine can be administered safely with high-dose cisplatin, vinblasti ne, and radiation therapy for NSCLC. The response rate and survival da ta provide no evidence that amifostine impairs response to treatment. Amifostine appears to reduce cisplatin-related nephrotoxicity and radi ation-induced esophagitis. (C) 1991 by American Society of Clinical On cology.