Intra-arterial carboplatin and intravenous etoposide for the treatment of metastatic brain tumors.

Abstract

Metastatic brain tumors (MBT) are the most frequent complication of systemic cancer and often respond poorly to treatment. Median survival is only 16-24 weeks after conventional radiation therapy. Regional intra-arterial (IA) administration of chemotherapy results in increased tumor uptake of drug and may improve response rates and survival. Twenty-seven patients with MBT who had received prior irradiation were treated with IA carboplatin (200 mg/m2/d) and intravenous (i.v.) etoposide (100 mg/m2/d) for 2 days every 3-4 weeks. Eighteen patients (67%) had received prior systemic chemotherapy for their primary tumor. Patients ranged in age from 19 to 68 years (mean 48.1). Thirteen of 24 evaluable patients had objective responses (54.2%). There were 6 complete responses (25%), 6 partial responses (25%), 1 minor response (4.2%), 7 stable disease (32%), and 5 progressive disease (20.8%). Some patients with multifocal tumors had a mixture of responses. The median time to progression was 16.0 weeks overall and 30.0 weeks in responders (range 6-118 weeks). Overall median survival from the time of protocol initiation was 20.0 weeks. In six responders, death occurred due to systemic illness unrelated to MBT progression. Therapy was well tolerated, with predominantly hematologic toxicity. Angiographic complications were rare. Although these are preliminary results, IA carboplatin and IV etoposide is safe and well tolerated, appears to be active against brain metastases, and warrants further study.