Ifosfamide in malignant mesothelioma: a phase II study

Malignant mesothelioma is a rare malignancy with a median survival, ranging from 4 to 18 months in untreated patients. In a phase II study of patients with mesothelioma, the efficacy and toxicity of ifosfamide and mesna was e valuated, Twenty-nine previously untreated patients, with histologically pr oven and unresectable mesothelioma, entered the study. Three patients were later excluded from the study due to revision of the diagnoses. The patient s had to have bidimensionally measurable disease by CT scans and a WHO perf ormance status less than or equal to 3. Eligible patients received ifosfami de 3000 mg/m(2) per day for 3 days as a 1-h infusion and mesna 1800 mg/m(2) per day for 3 days every third week. Dose modifications were made accordin g to the degree of hematologic, neurologic and renal toxicity. Response to treatment was evaluated in accordance with WHO criteria. The median age of patients was 59 years (range 39-68), 18 patients (69%) had a history of asb estos exposure and the median of treatment cycles was four (range 1-10). No complete responses were observed. One patient obtained a partial response after five cycles with a duration of response of 25 months. Nine patients ( 35%) had stable disease, while 13 (54%) progressed. The median survival for all patients was 10 months. The toxicity of the treatment was considerable . Thirteen patients (50%) had grade 4 leucopenia, ten patients (38%) had gr ade 3 or 4 reversible neurotoxicity and ten patients (38%) had grade 3 or 3 nausea and vomiting. Eleven patients (42%) went off the study due to the t oxicity of the treatment. In conclusion, ifosfamide did not show any substa ntial activity of relevance in malignant mesothelioma at the dose level inv estigated, in spite of considerable toxicity. (C) 1999 Elsevier Science Ire land Ltd. All rights reserved.