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 Koutcher, J. A. Articles by Martin, D. S. Search for Related Content PubMed PubMed Citation Articles by Koutcher, J. A. Articles by Martin, D. S.

Potentiation of a Three Drug Chemotherapy Regimen by Radiation¹

Departments of Medical Physics [J. A. K., A. A. A., M. L. D.], Radiology [J. A. K.], and Medicine [J. A. K., D. S. M.], Memorial Sloan Kettering Cancer Center, New York 10021, and Catholic Medical Center, Woodhaven 11421 [R. L. S., J. R. C., L. D. N., D. S. M.], New York

The combination of N-(phosphonacetyl)-L-aspartate, 6-methylmercaptopurine, and 6-aminonicotinamide has been shown to be an effective antineoplastic regimen and also to enhance the effects of other chemotherapeutic agents. The mechanism of action of this combination of drugs is not known definitively, but one possible mechanism is biochemical modulation of energy metabolism and inhibition of production of tumor ATP. Tumor-bearing mice were treated with N-(phosphonacetyl)-L-aspartate, followed 17 h later by 6-methylmercaptopurine and 6-aminonicotinamide. ³¹P nuclear magnetic resonance spectroscopic studies demonstrated a significant depletion of high energy phosphates at 10 h post-6-methylmercaptopurine and 6-aminonicotinamide. The addition of radiation at this time was shown to induce a significantly longer tumor growth delay and a greater number of regressions (including durable complete regressions) than either chemotherapy or radiation alone. The combination of chemotherapy and radiation was found to be supra-additive compared to the antineoplastic effects of either modality administered separately, without a measurable increase in host toxicity.

¹ This work was supported by USPHS Grant CA 25842 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Received 12/ 7/92. Accepted 5/21/93.

This article has been cited by other articles:

				D. S. Martin, J. R. Bertino, and J. A. Koutcher ATP Depletion + Pyrimidine Depletion Can Markedly Enhance Cancer Therapy: Fresh Insight for a New Approach Cancer Res., December 1, 2000; 60(24): 6776 - 6783. [Full Text]