Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial.

ABSTRACT

PURPOSE: To evaluate the safety profile and efficacy of whole brain radiotherapy (WBRT) concomitantly with temozolomide (TMZ) in patients with brain metastases (BM). METHODS AND MATERIALS Patients with BM were randomly assigned to 30 Gy of WBRT with or without concomitant TMZ (75 mg/m(2)/d) plus two cycles of TMZ (200 mg/m(2)/d for 5 days). The primary outcome was analysis of neurologic toxicity. The primary efficacy measures were 90-day progression-free survival of BM and the radiologic response at Days 30 and 90. RESULTS: We enrolled 82 patients. No neurologic acute toxicity was observed. Grade 3 or worse hematologic toxicity was seen in 3 patients and Grade 3 or worse vomiting in 1 patient of the WBRT plus TMZ arm. The objective response rate at 30 and 90 days and overall survival were similar in both arms. The percentage of patients with progression-free survival of BM at 90 days was 54% for WBRT vs. 72% for WBRT and TMZ (p = 0.03). Death from BM was greater in the WBRT arm (69% vs. 41%, p = 0.03). CONCLUSION: The concomitant use of RT with TMZ was well tolerated and resulted in significantly better progression-free survival of BM at 90 days. Although caution should be used, these results suggest TMZ could improve local control of BM.