Treatment > Etoposide · Temozolomide Clinical Trials

ASCO Proceedings, 2001 Annual Meeting, Abstract No. 2055. (Clinical Study)

Meeting Abstract

A Phase 1 Study of Temozolomide (Temodar) and Escalating Doses of Oral VP-16 for Adults with Recurrent Malignant Gliomas

David N Korones, Michal Benita-Weiss, Lazlo Mechtler, Peter Bushunow, Henry S Friedman

University of Rochester, Rochester, NY; Dent Neurological Institute, Buffalo, NY; Duke University, Durham, NC

Although Temozolomide is active against recurrent malignant gliomas, responses in many patients are modest and short-lived. Temozolomide may prove more effective in combination with other agents, and combination oral chemotherapy for these patients is a particularly attractive approach. 
We therefore conducted a phase 1 study of Temozolomide in combination with escalating doses of oral VP-16 to determine the maximum tolerated doses of these 2 agents when given together. 
The Temozolomide dose was fixed at 150 mg/m2/d days 1-5. 
The oral VP-16 was escalated in cohorts of 3 - 6 patients by numbers of days of VP-16 administered: 50 mg/m2/day, days 1-5 (dose level 1), days 1-8 (dose level 2), days 1-12 (dose level 3), and days 1-16 (dose level 4). 
Therapy was given in 28 day cycles. 
Twelve patients have thus far been enrolled and received a total of 34 cycles. 
The median age of the patients was 50 years (range 31-75 years). 
Diagnoses included 7 glioblastoma, 2 gliosarcoma, and 3 anaplastic astrocytoma. 
All patients had received prior radiation and 10 of 12 patients had received prior chemotherapy. 
Of the 3 patients receiving 6 courses at dose level 1, one had a grade 2 infection. 
Of the 6 patients receiving 22 courses at dose level 2, one patient had dose-limiting toxicity - grade 3 thrombocytopenia resulting in a 2 week delay in starting the next cycle of chemotherapy. 
Of the 3 patients receiving 6 courses at dose level 3, one had a grade 2 infection, and the other grade 2 emesis. 
Of the 34 cycles administered, there were four 1 week delays between cycles due to delayed recovery of blood counts. 
No doses of chemotherapy were missed. 
The maximum tolerated dose has not yet been reached. 
Of the 11 evaluable patients, 7 had progressive disease at 1, 1, 1, 2, 2, 3, and 3 months, and 4 have stable disease at 3+, 4+, 6+, and 7+ months. 
This regimen of combination oral chemotherapy is well-tolerated. 
A phase 2 trial of these agents will be conducted when the maximum tolerated dose of the combination is determined.

© Copyright 2001 American Society of Clinical Oncology. All rights reserved worldwide