Evaluation of chemotherapy and radiation enhancement and (31)P NMR spectral changes induced by biochemical modulation Journal Article
| Authors: | Koutcher, J. A.; Alfieri, A. A.; Tsai, J. C.; Matei, C.; Stolfi, R. L.; Ballon, D.; Martin, D. S. |
| Article Title: | Evaluation of chemotherapy and radiation enhancement and (31)P NMR spectral changes induced by biochemical modulation |
| Abstract: | The combination of N-(phosphonoacetyl)-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. |
| Keywords: | controlled study; doxorubicin; drug potentiation; nonhuman; mouse; animals; mice; cell division; breast cancer; antineoplastic combined chemotherapy protocols; animal experiment; animal model; drug synergism; disease progression; magnetic resonance spectroscopy; evaluation studies; radiation-sensitizing agents; energy metabolism; aspartic acid; nuclear magnetic resonance; intravenous drug administration; mammary neoplasms, experimental; phosphorus isotopes; intraperitoneal drug administration; sparfosic acid; 6 aminonicotinamide; female; priority journal; article; methylthioinosine; 6 methylthioinosine; 6-aminonicotinamide |
| Journal Title: | Cancer Investigation |
| Volume: | 15 |
| Issue: | 2 |
| ISSN: | 0735-7907 |
| Publisher: | Informa Healthcare |
| Date Published: | 1997-01-01 |
| Start Page: | 111 |
| End Page: | 120 |
| Language: | English |
| PUBMED: | 9095206 |
| PROVIDER: | scopus |
| DOI: | 10.3109/07357909709115763 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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