Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma

BACKGROUND. A single-institution Phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) and define the safety profile of temozolomide and capecitabine when used in combination to treat brain metastases from breast cancer. METHODS. Patients were eligible if they had bidimensionally measurable supratentorial or infratentorial brain metastasis from histologically confirmed breast carcinoma. Patients could have received up to 3 prior chemotherapy regimens. Temozolomide and capecitabine were administered concomitantly to 4 sequential cohorts at different dosing levels on Days 1-5 and Days 8-12, with cycles repeated every 21 days until disease progression. RESULTS. Twenty-four patients with multiple brain lesions were treated, including 14 patients with newly diagnosed brain metastases and 10 patients with recurrent brain metastases. Only 1 patient was chemotherapy-naive. Fatigue and nausea were the most commonly observed toxicities observed at any dose levels. Significant antitumor activity was observed, with a total of 1 complete and 3 partial responses (18% objective response rate) in the brain. The median response duration was 8 weeks (range, 6-64 weeks) and the median time to progression in the brain was 12 weeks (range, 3-70 weeks). Neurocognitive function improved or remained stable in patients with a response or stable disease. CONCLUSIONS. The combination of temozolomide and capecitabine is an active, well-tolerated regimen. The observed antitumor activity warrants further evaluation of this combination as an alternative to or in combination with whole-brain radiation therapy for the treatment of multiple brain metastases.