Evaluation of chemotherapy and radiation enhancement and 31P NMR spectral changes induced by biochemical modulation.

Publication Type	Academic Article
Authors	Koutcher J, Alfieri A, Tsai J, Matei C, Stolfi R, Ballon D, Martin D
Journal	Cancer Invest
Volume	15
Issue	2
Pagination	111-20
Date Published	01/01/1997
ISSN	0735-7907
Keywords	Antineoplastic Combined Chemotherapy Protocols, Magnetic Resonance Spectroscopy, Mammary Neoplasms, Experimental, Radiation-Sensitizing Agents
Abstract	The combination of N-(phosphonacetyl)-L-aspartate (PALA), 6-methylmercaptopurine riboside (MMPR), and 6-aminonicotinamide (6AN) has been shown to be an effective antineoplastic regimen and also to enhance the effects of other antineoplastic agents (1-4). To further enhance the effect of this combination, we investigated the effects of adding adriamycin, at its maximally tolerated dose, to this regimen. The response rate (complete regression+partial regression) for the four-drug regimen was higher than for the three-drug regimen, and the tumor growth delay was also significantly higher than for treatment with PALA, MMPR, 6AN, or after treatment with maximally tolerated doses of adriamycin alone (11 mg/kg). The addition of adriamycin to PALA, MMPR, 6AN did not result in enhancement of the effect of radiation, as measured by tumor growth delay studies and tumor control (complete and partial regression rate). The mechanism of action of the combination of PALA, MMPR, and 6AN is not known definitively, but a possible mechanism previously suggested is biochemical modulation of energy metabolism and inhibition of production of tumor ATP. Treatment with PALA, MMPR, 6AN, and adriamycin (at 2.5 hr post MMPR, 6AN) resulted in a nadir NTP/Pi value, as determined by 31P NMR spectroscopy, at approximately 10 hr post MMPR + 6AN (7.5 hr post adriamycin), which was not significantly different from the NTP/Pi value determined after treatment with the three-drug combination.
DOI	10.3109/07357909709115763
PubMed ID	9095206