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 therapeuticadvantages. PATIENTS AND METHODS:: A total of 68 patients with advanced non-small-cell lung cancer,not previously treated by chemotherapy, were randomized to receiveeither ifosfamide given orally (OSI) at a dose of 1 g/day for14 days every 4 weeks, or as a 1-hour intravenous infusion (IVI)at a dose of 1.6 g/m²/day for 5 days every 4 weeks. Accordingto the route of ifosfamide administration, patients receivedeither mesna i.v. or mesna film-coated tablets for uroprotection. RESULTS:: Eight patients were found to be ineligible for the study andtherefore excluded for all analyses. Thirty-three patients receivedIVI, and 27 patients OSI. One patient randomized to OSI diedbefore treatment was initiated, leaving 59 patients fully evaluablefor toxicity. Hematological toxicity was less severe for patientson OSI, but CNS toxicity was reported more frequently on OSI(39%; 12% grade III/IV), than on 1VI (15%; 9% grade III/IV),which caused the premature close of the study. Other non-hematologicaladverse events were of modest clinical significance and comparablein both arms. Forty-nine patients were considered evaluablefor response: in the IVI arm, 5 (17%) of the 29 evaluable patientsobtained a partial remission, and 7 patients a no change (24%).In the OSI arm, 2 (10%) of the 20 evaluable patients obtaineda partial remission, and 11(52%) a stable disease. CONCLUSION:: Both arms have some activity in non-small-cell lung cancer;while OSI was less myelosuppressive than IVI, it was associatedwith a higher incidence of CNS toxicity. Oral administrationof ifosfamide, in the schedule and daily dose tested here cannotbe recommended. chemotherapy, ifosfamide, non-small-cell lung cancer, phase II trial