Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in the treatment of cerebral metastasis

BACKGROUND: Cerebral metastases are clinically significant in 10% to 30% of patients with neoplasia. Multiple cerebral metastases are typically treated with palliative radiotherapy. There is no consensus on the role of enhanced chemotherapy delivery as an adjuvant treatment modality in this disease. In this report, the authors detailed their experience with intraarterial (IA) chemotherapy infusion with and without blood-brain barrier disruption (BBBD) in patients with multiple cerebral metastases. METHODS: From November 1999 to May 2005, 38 patients with multiple cerebral metastases were enrolled in a prospective study. Patients were treated with IA carboplatin, except for those with cerebral metastases of systemic lymphoma, who were administered IA methotrexate. Osmotic BBBD was offered to patients without the presence of a significant mass effect. These regimens were coupled with intravenous etoposide and cyclophosphamide. Cycles were repeated every 4 weeks. RESULTS: Survival was calculated from study entry and radiologic response was based on MacDonald criteria. Kaplan-Meier estimates were generated for all subgroups. Mean and median survival obtained was as follows: 34 and 29.6 months for the whole group; 33.6 and 42.3 months for ovarian carcinoma; 15.3 and 13.5 months for lung adenocarcinomas; 8.3 and 8.8 months for small cell lung carcinoma; 8.9 and 8.1 months for breast carcinoma; and 24.8 and 16.3 months, respectively, for cerebral metastasis from systemic lymphoma. CONCLUSIONS: Even with a small number of patients in each subgroup, the results obtained seem promising for multiple brain metastasis of ovarian carcinoma, adenocarcinoma of lung, small cell lung carcinoma, and systemic lymphoma.