This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ewend, M. G. Articles by Brem, H. Search for Related Content PubMed PubMed Citation Articles by Ewend, M. G. Articles by Brem, H.

Local Delivery of Chemotherapy and Concurrent External Beam Radiotherapy Prolongs Survival in Metastatic Brain Tumor Models¹

Hunterian Neurosurgical Laboratory, Department of Neurosurgery [M. G. E., J. A. W., K. T., B. M. T., K. M. B., R. C. A., M. L. P., H. B.], Department of Oncology [H. B.], Division of Radiation Oncology [J. A. W.], and Department of Pathology, [D. J. B.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. However, use of local chemotherpy 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.

¹ Supported in part by the National Cooperative Drug Discovery Group (UO1-CA52857) of the National Cancer Institute of the National Institutes of Health, Bethesda, Maryland.

² Dr. Ewend is a recipient of the NIH National Research Service Award CA-09574.

³ To whom requests for reprints should be addressed, at Department of Neurosurgery, Hunterian Neurosurgical Laboratory, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Hunterian 817, Baltimore, MD 21205.

Received 7/ 2/96. Accepted 9/17/96.

This article has been cited by other articles:

				M. G. Ewend, S. Brem, M. Gilbert, R. Goodkin, P. L. Penar, M. Varia, S. Cush, and L. A. Carey Treatment of Single Brain Metastasis with Resection, Intracavity Carmustine Polymer Wafers, and Radiation Therapy Is Safe and Provides Excellent Local Control Clin. Cancer Res., June 15, 2007; 13(12): 3637 - 3641. [Abstract] [Full Text] [PDF]

				Q. Wu, B. Tyler, L. Sukay, L. Rhines, F. DiMeco, R. E. Clatterbuck, M. Guarnieri, and B. S. Carson Sr. Experimental Rodent Models of Brainstem Tumors Vet. Pathol., May 1, 2002; 39(3): 293 - 299. [Abstract] [Full Text] [PDF]

				D. C. Bowers, S. Fan, K. A. Walter, R. Abounader, J. A. Williams, E. M. Rosen, and J. Laterra Scatter Factor/Hepatocyte Growth Factor Protects against Cytotoxic Death in Human Glioblastoma via Phosphatidylinositol 3-Kinase- and AKT-dependent Pathways Cancer Res., August 1, 2000; 60(15): 4277 - 4283. [Abstract] [Full Text]

				P. Sampath, J. Hanes, F. DiMeco, B. M. Tyler, D. Brat, D. M. Pardoll, and H. Brem Paracrine Immunotherapy with Interleukin-2 and Local Chemotherapy Is Synergistic in the Treatment of Experimental Brain Tumors Cancer Res., May 1, 1999; 59(9): 2107 - 2114. [Abstract] [Full Text] [PDF]