Treatment > Etoposide · Temozolomide Clinical Trials

38th ASCO Annual Meeting. Orlando, FL. May 18-21, 2002. Abstract No. 2080 (Clinical Study)

Meeting Abstract

A phase I study of temozolomide (Temodar) and escalating doses of oral VP-16 for adults with recurrent malignant glioma

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

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

Although temozolomide is active against recurrent malignant glioma, 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 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), days 1-16 (dose level 4) and days 1-20 (dose level 5). Therapy was given in 28 day cycles. 
Of the 29 patients enrolled, 26 were fully evaluable and 3 partially evaluable for toxicity. 
The 29 patients received a total of 79 cycles. 
The median age of the patients was 49 years (range 28-76 years). 
Diagnoses include glioblastoma (19), gliosarcoma (3), anaplastic astrocytoma (5), and anaplastic oligoastrocytoma (2). 
The median time from diagnosis to recurrence was 8 months (3-188 mo.). 
Twenty patients were treated at first recurrence, 7 at second, and 2 at third recurrence. 
Twenty-four patients (83%) were on anti-convulsants, and 24 were on dexamethasone. 
All patients had received prior radiation and 25 of 29 had prior chemotherapy. 
Of the 3 patients at dose level 1, none had dose-limiting toxicity. 
Of the 6 patients at dose level 2, one patient had dose-limiting toxicity (DLT) - grade 3 thrombocytopenia resulting in a > 2 week delay in starting the next cycle of chemotherapy. 
Of the 6 patients at dose level 3, one patient had DLT– death due to Pneumocystis pneumonia. 
There were 2 DLT’s in the 7 patients at dose level 4 – death due to pneumonia, and fever, neutropenia, and Zoster. 
Of the 5 fully evaluable and 2 partially evaluable patients at dose level 5, there was no DLT. 
The maximum tolerated dose of this combination in this heavily treated group of patients with recurrent malignant glioma is temozolomide 150 mg/m2/d for 5 days + oral VP-16 50 mg/m2/d for 12 days. 
A phase II study of this combination is currently being conducted.

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