LOCAL-DELIVERY OF CHEMOTHERAPY AND CONCURRENT EXTERNAL-BEAM RADIOTHERAPY PROLONGS SURVIVAL IN METASTATIC BRAIN-TUMOR MODELS

Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. Ho wever, use of local chemotherapy for metastatic brain tumors has not b een defined. We studied the safety and the efficacy of locally deliver ed chemotherapy with and without concurrent radiation therapy in treat ing tumors that frequently metastasize to the brain. The chemotherapeu tic agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), carboplatin, a nd camptothecin were incorporated into controlled-release polymers and tested individually against intracranial challenges with one of four tumors (lung carcinoma, renal cell carcinoma, colon carcinoma, and mel anoma). For each combination of drug and tumor type, four groups were tested: (a) empty polymer (no drug); (b) external beam radiotherapy (X RT) alone; (c) local chemotherapy from biodegradable polymer alone; an d (d) local chemotherapy and XRT together. Polymers were implanted 5 d ays after tumor inoculation; XRT was given on days 7-9 (300 cGy/day). BCNU and XRT together were effective against all four tumors. BCNU pol ymer alone significantly prolonged survival in mice with intracranial melanoma or renal cell carcinoma. Carboplatin alone was effective agai nst both melanoma and colon carcinoma and in combination with XRT agai nst colon and renal cell carcinomas. Camptothecin was effective only w ith XRT against melanoma. These studies demonstrate that local deliver y of chemotherapy with concurrent radiation therapy is safe and can si gnificantly prolong survival in models of common intracranial metastat ic tumors. Concurrent use of local chemotherapy with standard XRT appe ars to be more effective than either treatment alone. Local chemothera py may also be of benefit to patients who have previously received max imal cranial irradiation but suffer an intracranial recurrence.