Potentiation of a three drug chemotherapy regimen by radiation

• Published in: Cancer research (Chicago, Ill.) Ill.), 1993-08, Vol.53 (15), p.3518-3523
• Main Authors: KOUTCHER, J. A, ALFIERI, A. A, STOLFI, R. L, DEVITT, M. L, COLOFIORE, J. R, NORD, L. D, MARTIN, D. S
• Format: Article
• Language: English
• Subjects: 6-Aminonicotinamide - administration & dosage; Animals; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Aspartic Acid - administration & dosage; Aspartic Acid - analogs & derivatives; Biological and medical sciences; Combined Modality Therapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Female; Medical sciences; Mercaptopurine - administration & dosage; Mercaptopurine - analogs & derivatives; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Neoplasm Transplantation; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - radiotherapy; Neoplasms, Experimental - therapy; Pharmacology. Drug treatments; Phosphonoacetic Acid - administration & dosage; Phosphonoacetic Acid - analogs & derivatives
• ISSN: 0008-5472; 1538-7445

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.