A Phase I Study of Temozolomide and CCNU in Pediatric Patients With Newly Diagnosed Incompletely Resected Non-Brainstem High-Grade Gliomas

OBJECTIVES:

• Determine the maximum tolerated dose of temozolomide when administered with lomustine in patients with high-grade malignant gliomas.
• Determine the dose-limiting toxic effects of this regimen in these patients.
• Evaluate the feasibility of radiotherapy after this treatment regimen in this patient population.
• Evaluate the radiographic responses in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of temozolomide.

Patients receive oral temozolomide on days 1-5 and oral lomustine on day 1. Treatment continues every 28 days, if blood counts have recovered, for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy on days 1-5 weekly for 6 weeks. Patients continue the same chemotherapy regimen for up to 6 more courses beginning 4 weeks after completion of radiotherapy.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.