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Local delivery of chemotherapy and concurrent external beam radiotherapy prolongs survival in metastatic brain tumor models.

Abstract：

:Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. However, use of local chemotherapy for metastatic brain tumors has not been defined. We studied the safety and the efficacy of locally delivered chemotherapy with and without concurrent radiation therapy in treating tumors that frequently metastasize to the brain. The chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), carboplatin, and 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 melanoma). For each combination of drug and tumor type, four groups were tested: (a) empty polymer (no drug); (b) external beam radiotherapy (XRT) alone; (c) local chemotherapy from biodegradable polymer alone; and (d) local chemotherapy and XRT together. Polymers were implanted 5 days after tumor inoculation; XRT was given on days 7-9 (300 cGy/day). BCNU and XRT together were effective against all four tumors. BCNU polymer alone significantly prolonged survival in mice with intracranial melanoma or renal cell carcinoma. Carboplatin alone was effective against both melanoma and colon carcinoma and in combination with XRT against colon and renal cell carcinomas. Camptothecin was effective only with XRT against melanoma. These studies demonstrate that local delivery of chemotherapy with concurrent radiation therapy is safe and can significantly prolong survival in models of common intracranial metastatic tumors. Concurrent use of local chemotherapy with standard XRT appears to be more effective than either treatment alone. Local chemotherapy may also be of benefit to patients who have previously received maximal cranial irradiation but suffer an intracranial recurrence.

journal_name

Cancer Res

journal_title

Cancer research

authors

Ewend MG,Williams JA,Tabassi K,Tyler BM,Babel KM,Anderson RC,Pinn ML,Brat DJ,Brem H

subject

Has Abstract

pub_date

1996-11-15 00:00:00

pages

5217-23

issue

eissn

0008-5472

issn

1538-7445

journal_volume

pub_type

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Local delivery of chemotherapy and concurrent external beam radiotherapy prolongs survival in metastatic brain tumor models.