Overview of N-(phosphonacetyl)-L-aspartate + fluorouracil in clinical trials.
The clearest example of successful biochemical modulation of cancer chemotherapy in the laboratory, followed by initial failure to reproduce successful therapeutic results in the clinic, and then eventually followed by clinical success, is that of the combination of N-(phosphonacetyl)-L-aspartate (PALA) and fluorouracil (5-FU). This review covers the biochemistry involved, the preclinical findings, the many clinical trials, and explains the differences between the initial unsuccessful and the later successful clinical studies. The overall findings demonstrate that, to be successful, the design of modulation-based clinical trials should adhere to the principles determined in preclinical studies.
Martin
D S
DS
Department of Medicine, Memorial Sloan Kettering Cancer Center, Cornell University Medical College, New York, NY.
Kemeny
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NE
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism; D005544:Forecasting; D006801:Humans; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives
D000964:Antimetabolites, Antineoplastic; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil