PHASE II STUDY OF IFOSFAMIDE IN MALIGNANT MESOTHELIOMA

Andersen MK¹, Krarup-Hansen A¹, Mårtensson G², Winther-Nielsen H³, Thylen A², Damgaard K⁴, Olling O⁵, Wallin J⁶. (Dept. of Oncology¹, Dept. of Pathology³, Dept of Radiology⁴, National University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark, Dept. of Pulmonary Medicine², Sahlgrenska University Hospital, Dept. of Pathology⁵, Dept. of Radiology⁶, Ostra Sjukhuset, Goteborg, Sweden.

Introduction: Malignant mesothelioma is a rare malignancy with a median survival typical ranging from 4 to 18 months in untreated patients. No standard therapy has been established.

Material & Methods: In a phase II study of patients with mesothelioma the efficacy and toxicity of ifosfamide and mesna was evaluated. The patients had to have bidimensionally measurable disease by CT scans and a WHO performance status ( 3. Eligible patients received ifosfamide 3 g/m2 per day for 3 days as a one-hour infusion and mesna 1.8 g/m2 per day for 3 days every third week. Dose modifications were made according to the degree of hematologic, neurologic, and renal toxicity. Response to treatment was evaluated in accordance to WHO criteria.

Results: Twenty-nine previously untreated patients with histologically proven and unresectable mesothelioma entered the study. Three patients were excluded from the study due to revision of the diagnoses. The median age of patients was 59 years (range 39-68), 18 patients (69%) had a history of asbestos exposure, and the median of treatment cycles was 4 (range 1-10). No complete responses were observed. One patient obtained a partial response after 5 cycles with 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, 10 patients (38%) had grade 3 or 4 reversible neurotoxicity, and 10 patients (38%) had grade 3 or 4 nausea and vomiting. Eleven patients (42%) went off study due to toxicity of the treatment.

Conclusion: Ifosfamide did not show any substantial activity of relevance in malignant mesothelioma at the dose level investigated, in spite of considerable toxicity.