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Phase I study of N-(phosphonacetyl)-L-aspartic acid (PALA).

Abstract
N-(Phosphonacetyl)-L-aspartic acid, an inhibitor of aspartate transcarbamylase, was administered to 25 patients with advanced cancer by 10-minute infusion daily x 5 consecutive days to determine the toxicity and to look for evidence of therapeutic effect. Planned dose escalations ranged from 100 to 1250 mg/m2 (daily dose). Nausea, vomiting, and diarrhea were the most frequent toxic effects, with three of six patients treated at a daily dose of 1250 mg/m2 having severe diarrhea. Other toxic effects were encountered rarely and were not dose-limiting; these included mild leukopenia, thrombocytopenia, rash, stomatitis, and increases in SGOT. One patient with a widely metastatic carcinoid of unknown origin had an objective response lasting 6 weeks.
AuthorsJ S Kovach, A J Schutt, C G Moertel, M J O'Connell
JournalCancer treatment reports (Cancer Treat Rep) 1979 Nov-Dec Vol. 63 Issue 11-12 Pg. 1909-12 ISSN: 0361-5960 [Print] United States
PMID526923 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Organophosphorus Compounds
  • Aspartic Acid
  • sparfosic acid
  • Phosphonoacetic Acid
Topics
  • Adult
  • Aged
  • Aspartic Acid (analogs & derivatives, therapeutic use, toxicity)
  • Bone Marrow (drug effects)
  • Carcinoid Tumor (drug therapy)
  • Diarrhea (chemically induced)
  • Drug Evaluation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms (drug therapy)
  • Organophosphorus Compounds (therapeutic use)
  • Phosphonoacetic Acid (analogs & derivatives, therapeutic use, toxicity)
  • Vomiting (chemically induced)

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