Phase I/II dose escalation trial of concurrent temozolomide and whole brain radiation therapy for multiple brain metastasis.

This study sought to establish the recommended phase II dose and efficacy of temozolomide (TMZ) with concurrent radiotherapy in patients with brain metastases. Patients were stratified by prior systemic therapy (≤1 vs. ≥2) and enrolled in cohorts of escalating doses of daily TMZ for 14 days (group A: 75, 95, 115, 135, or 150 mg/m(2), group B: 75, 90, 105, 120, or 135 mg/m(2)). Endpoints included safety and clinical activity. For group A (≤1 prior chemotherapy) no dose limiting toxicity was seen at 75 and 95 mg/m(2). Five of eight patients experienced dose limiting toxicities at 115 mg/m(2), thus the recommended phase II dose was 95 mg/m(2). Arm B (≥2 prior chemotherapy regimens) was closed due to poor enrollment. In the phase II portion, 17 patients in group A were treated. There were 0 patients with complete radiographic response, three with a partial response, ten remained stable, and four demonstrated early progression. The 3 and 6 month progression-free survival (PFS) rates were 41 and 18% with a median PFS time of 2.4 months. Overall survival at 3 and 6 months was 53 and 41%, respectively, with a median survival time of 4.1 months. The maximum tolerated dose of daily TMZ with concurrent WBRT was 95 mg/m(2). Despite dose escalation, outcomes did not appear to be improved in the sample treated.