Temozolomide Enhances Radiation Treatment Efficacy in Brain Metastases: a Randomized Phase II Study.
D Antonadou, M Paraskevaides, N Coliarakis, G Sarris, P Karageorgis, N Throuvalas, Hellenic Group Clinical Radiation Oncology, Kifisia, Greece.
Presented at the American Society Of Clinical Oncology, 2001 Conference

Brain metastases occur in 20%–40% of all cancer patients, most often as multiple lesions rather than as a single metastasis. While radiation treatment (XRT) remains the most effective recourse, only modest gains in survival are achieved despite high initial response rates. [Para]A randomized study was conducted to evaluate the efficacy and safety of concurrent administration of temozolomide (TMZ), an oral cytotoxic agent that crosses the blood-brain barrier, and XRT in patients with previously untreated brain metastases. Patients with histologically proven lung or breast cancer and brain metastases were randomly allocated to treatment with TMZ 75 mg/m2 daily during conventional XRT 2 Gy/5 days/week for a total dose of 40 Gy or to XRT alone (control). In the TMZ + XRT group, 200 mg/m2 TMZ was administered 1 month post XRT for 5 consecutive days every 28 days for 6 cycles. The primary endpoint was radiological response as assessed by CT scan or MRI and neurological symptom evaluation at 2 months post XRT. [Para]To date, 48 evaluable patients have been enrolled. The groups did not differ significantly in primary tumor site, age, gender, and performance status. No grade 3 toxicity occurred. Thus far, 45 patients have been evaluated for response by radiological assessment (24 in the TMZ + XRT group and 21 in the XRT only [control] group). In the TMZ + XRT arm 38% of patients achieved a complete response and 58% achieved a partial response versus 33% and 33%, respectively, in the control arm (p = 0.017). At baseline, neurological evaluation showed 24% of patients in the TMZ + XRT group and 26% of patients in the control group were fully functional. After treatment, the percentages of patients who were fully functional were 46% and 38%, respectively (p = 0.653). These preliminary results indicate that combined treatment with TMZ and XRT is well tolerated and enhances XRT efficacy in brain metastases.