CONCURRENT RADIOCHEMOTHERAPY WITH IFOSFAMIDE IN UNRESECTABLE STAGE-III NON-SMALL-CELL LUNG-CANCER

Background: The purpose of this phase I/II study was to evaluate the e ffects of concurrently and continuously administered ifosfamide and ir radiation on side effects and tumor response in patients with unresect able or medically inoperable stage III non-small-cell lung cancer (NSC LC). Patients and Methods: A total of 36 patients with stage III NSCLC , not previously treated, entered the study. Ifosfamide at four differ ent dose levels (level I: 500 mg/m(2)/day; level II: 1,000 mg/m(2)/day ; level III: 1,500 mg/m(2)/day; level IV: 1,800 mg/m(2)/day) was admin istered as 24-hour continuous infusion over 5 days during the Ist and the 5th week of radiotherapy (total dose 60 Gy with daily single doses of 2 Gy). Mesna was given intravenously for uroprotection. Results: A nalysis of toxicity and response rates is based on 36 patients. 29 pat ients (81%) were completely treated according to the protocol. During phase I (with 22 patients), hematological toxicity was mild for dose l evel I-II, moderate for level III, and severe for level IV (100% grade III and IV leukopenia). Therefore, phase II of the study (with anothe r 14 patients) was conducted with a dose level of 1,500 mg/m(2)/day if osfamide. Pneumonitis was the major non-hematological sequela, but not increased compared with usual rates for radiotherapy alone. Other non hematological toxicities were generally mild with the exception of alo pezia. The overall response rate of the patients who completed the pro tocol was 97% (8 patients with complete remission; 20 patients with pa rtial remission). Median survival time of all patients was 10.7 months . The 1-year and 2-year survival rates were 47% and 22%, respectively. Conclusions: These results show that concurrent radiochemotherapy wit h ifosfamide is feasible. The response rate and the 2-year survival ra te were in same order of magnitude than those obtained with radiochemo therapy protocols employing cisplatin.