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

Jason A. Koutcher, Alan A. Alfieri, Jason C. Tsai, Cornelia Matei, Robert L. Stolfi, Douglas Ballon, Daniel S. Martin

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalCancer Investigation
Volume15
Issue number2
StatePublished - 1997
Externally publishedYes

Fingerprint

6-Aminonicotinamide
NSC 224131
Radiation
Doxorubicin
Drug Therapy
Maximum Tolerated Dose
Antineoplastic Agents
Methylthioinosine
Neoplasms
Radiation Effects
Drug Combinations
Growth
Pharmaceutical Preparations
Energy Metabolism
6-methylthiopurine
Magnetic Resonance Spectroscopy
Therapeutics
Adenosine Triphosphate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Koutcher, J. A., Alfieri, A. A., Tsai, J. C., Matei, C., Stolfi, R. L., Ballon, D., & Martin, D. S. (1997). Evaluation of chemotherapy and radiation enhancement and 31P NMR spectral changes induced by biochemical modulation. Cancer Investigation, 15(2), 111-120.

Evaluation of chemotherapy and radiation enhancement and 31P NMR spectral changes induced by biochemical modulation. / Koutcher, Jason A.; Alfieri, Alan A.; Tsai, Jason C.; Matei, Cornelia; Stolfi, Robert L.; Ballon, Douglas; Martin, Daniel S.

In: Cancer Investigation, Vol. 15, No. 2, 1997, p. 111-120.

Research output: Contribution to journalArticle

Koutcher, JA, Alfieri, AA, Tsai, JC, Matei, C, Stolfi, RL, Ballon, D & Martin, DS 1997, 'Evaluation of chemotherapy and radiation enhancement and 31P NMR spectral changes induced by biochemical modulation', Cancer Investigation, vol. 15, no. 2, pp. 111-120.
Koutcher JA, Alfieri AA, Tsai JC, Matei C, Stolfi RL, Ballon D et al. Evaluation of chemotherapy and radiation enhancement and 31P NMR spectral changes induced by biochemical modulation. Cancer Investigation. 1997;15(2):111-120.
Koutcher, Jason A. ; Alfieri, Alan A. ; Tsai, Jason C. ; Matei, Cornelia ; Stolfi, Robert L. ; Ballon, Douglas ; Martin, Daniel S. / Evaluation of chemotherapy and radiation enhancement and 31P NMR spectral changes induced by biochemical modulation. In: Cancer Investigation. 1997 ; Vol. 15, No. 2. pp. 111-120.
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