Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases

Purpose: To determine the efficacy, tolerability, and safety of temozolomid e in heavily pretreated patients with solid tumors and brain metastases. Patients and methods: Twenty-seven of twenty-eight enrolled patients with b rain metastases from solid tumors received temozolomide (150 mg/m(2)/day fo r five days every 28 days). Twelve patients had non-small-cell lung cancer, five patients had small-cell lung cancer, four patients had breast cancer, and seven patients had other solid tumors. The majority of the patients ha d multiple metastatic sites, a poor performance status, and had been heavil y pretreated. The primary end points were objective response rate, time to progression, and overall survival. Secondary end points included safety and tolerability, and neurologic performance status. Results: A partial response was achieved in 1 (4%) of 24 evaluable patients . Disease stabilization was observed in four (17%) patients. Overall median survival was 4.5 months and median time to progression was 3 months. Impro vements in clinical neurologic status were achieved in 10 (37%) patients. T reatment with temozolomide was well tolerated. Four patients had grade 3 na usea and vomiting. No grade 4 toxicity or treatment-related deaths were obs erved. Conclusions: Temozolomide demonstrated encouraging activity in the treatmen t of brain metastases in heavily pretreated patients with solid tumors, and was safe and well tolerated.