Oral ifosfamide/mesna versus intravenous ifosfamide/mesna in non-small-cell lung cancer: A randomized phase II trial of the EORTC lung cancer cooperative group

Background: Chronic oral administration of anticancer drugs may offer therapeutic advantages. Patients and methods: A total of 68 patients with advanced non-small-cell lung cancer, not previously treated by chemotherapy, were randomized to receive either ifosfamide given orally (OSI) at a dose of 1 g/day for 14 days every 4 weeks, or as a 1-hour intravenous infusion (IVI) at a dose of 1.6 g/m(2)/day for 5 days every 4 weeks. According to the route of ifosfamide administration, patients received either mesna i.v. or mesna film-coated tablets for uroprotection. Results: Eight patients were found to be ineligible for the study and therefore excluded for all analyses. Thirty-three patients received IVI, and 27 patients OSI. One patient randomized to OSI died before treatment was initiated, leaving 59 patients fully evaluable for toxicity. Hematological toxicity was less severe for patients on OSI, but CNS toxicity was reported more frequently on OSI (39%; 12% grade III/IV), than on IVI (15%; 9% grade III/IV), which caused the premature close of the study. Other non-hematological adverse events were of modest clinical significance and comparable in both arms. Forty-nine patients were considered evaluable for response: in the M arm, 5 (17%) of the 29 evaluable patients obtained a partial remission, and 7 patients a no change (24%). In the OSI arm, 2 (10%) of the 20 evaluable patients obtained a partial remission, and 11 (52%) a stable disease. Conclusions: Both arms have some activity in non-small-cell lung cancer; while OSI was less myelosuppressive than IVI, it was associated with a higher incidence of CNS toxicity. Oral administration of ifosfamide, in the schedule and daily dose tested here cannot be recommended.