Potentiation of a Three Drug Chemotherapy Regimen by Radiation

Jason A. Koutcher, Alan A. Alfieri, Robert L. Stolfi, Mary L. Devitt, Joseph R. Colofiore, L. Dee Nord, Daniel S. Martin

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The combination of N-(phosphonacetyl)-L-äspartate, 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-äspartate, 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-methylmer-captopurine 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.

Original languageEnglish (US)
Pages (from-to)3518-3523
Number of pages6
JournalCancer Research
Volume53
Issue number15
StatePublished - Aug 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Koutcher, J. A., Alfieri, A. A., Stolfi, R. L., Devitt, M. L., Colofiore, J. R., Nord, L. D., & Martin, D. S. (1993). Potentiation of a Three Drug Chemotherapy Regimen by Radiation. Cancer Research, 53(15), 3518-3523.