THIOTEPA AND ETOPOSIDE TREATMENT OF RECURRENT MALIGNANT GLIOMAS - PHASE-I STUDY

Purpose: To determine: (1) the maximum tolerable dose (MTD) of thiotep a (TT) that can be administered with etoposide without stem cell suppo rt; (2) whether this is active against recurrent malignant gliomas. Ba ckground: Although several chemotherapeutic agents show minor activity against recurrent brain tumors, there is no consensus about the most effective regimen. The alkylating agent TT has excellent central nervo us system (CNS) penetration and is synergistic with the topoisomerase II inhibitor etoposide. Design/Methods: Fifteen patients with recurren t malignant gliomas (14 glioblastomas, 1 anaplastic astrocytoma) recei ved intravenous etoposide 100 mg/m(2) on days 1, 2, and 3, and intrave nous TT (40, 50, 60, or 70 mg/m(2)) on day 2. All had received irradia tion, and eight BCNU. Chemotherapy was repeated every 3-4 weeks, with stepwise TT dose increments of 10 mg/m(2), provided toxicity was less than grade III. Results: The major toxicity was dose-limiting leukopen ia. The MTD of TT in cycle 1 was 60 mg/m(2). All patients died of prog ressive disease and none died of chemotherapy-related complications. C onclusions: The MTD of TT in this regimen for recurrent malignant glio mas is 60 mg/m(2). Higher doses of TT would require colony-stimulating factors or stem cell support.