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 effects of concurrently and continuously administered ifosfamide and irradiation on side effects and tumor response in patients with unresectable or medically inoperable stage III non-small-cell lung cancer (NSCLC). Patients and Methods: A total of 36 patients with stage III NSCLC, not previously treated, entered the study. Ifosfamide at four different 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 administered 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: Analysis of toxicity and response rates is based on 36 patients. 29 patients (81%) were completely treated according to the protocol. During phase I (with 22 patients), hematological toxicity was mild for dose level I-II, moderate for level III, and severe for level IV (100% grade III and IV leukopenia). Therefore, phase II of the study (with another 14 patients) was conducted with a dose level of 1,500 mg/m(2)/day ifosfamide. Pneumonitis was the major non-hematological sequela, but not increased compared with usual rates for radiotherapy alone. Other nonhematological toxicities were generally mild with the exception of alopezia. The overall response rate of the patients who completed the protocol was 97% (8 patients with complete remission; 20 patients with partial 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 with ifosfamide is feasible. The response rate and the 2-year survival rate were in same order of magnitude than those obtained with radiochemotherapy protocols employing cisplatin.