Treatment of recurrent malignant supratentorial gliomas with ifosfamide, carboplatin and etoposide: a phase II study.

Thirty-six patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of ifosfamide, carboplatin and etoposide (ICE) at tumour progression. Carboplatin and etoposide were both given at a dose of 75-100 mg/m2/day for 3 days, whereas ifosfamide doses ranged from 750 mg/m2/day to 1500 mg/m2/ day for 3 days, according to haematological tolerance. Treatment was repeated every 4 weeks. A minimum of three courses was required to evaluate the response unless the patient had rapid tumour progression. Grade III and IV haematological toxicity occurred in 15 patients (42%) and was lethal in one patient. Grade II hepatic toxicity was observed in one patient. Five complete (CR) and five partial responses (PR) were noted. 9 patients had stable disease (SD) after a minimum of three courses. CR + PR + SD was 53% (19/36). The median time to tumour progression (MTTP) was 13 weeks. Median survival (MST) was 29 weeks (44 weeks for R + S patients and 17 weeks for patients with progressing disease). This study suggests that the ICE combination is active in recurrent supratentorial malignant gliomas after failure of surgery, radiation therapy and chemotherapy, but at the cost of substantial haematological toxicity.