C. Balmaceda et al., THIOTEPA AND ETOPOSIDE TREATMENT OF RECURRENT MALIGNANT GLIOMAS - PHASE-I STUDY, Cancer chemotherapy and pharmacology, 40(1), 1997, pp. 72-74
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.