Phase i trial of n-(phosphonacetyi)-l-aspartate

Charles Erlichman, John M. Strona, Peter H. Wiernik, Linda M. McAvov, Martin H. Cohen, Arthur S. Levine, Susan M. Hubbard, Bruce A. Chabner

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

A Phase I clinical trial of N-(phosphonacetyI)-L-aspartate an antimetabolite which inhibits a key enzyme in the de novo pathway of pyrimidine biosynthesis, was conducted. N-(Phos-phonacety1)4.-aspartate was given as an i.v. 15-min infusion once daily for five days; cycles of treatment were repeated every three weeks. Thirty-four patients received treatment. Dose-limiting toxicity was observed at 1500 to 2000 mg/sq m/day and was manifested by skin rash, diarrhea, and stomatitis. Rash and diarrhea usually began during the first week of treatment and persisted up to Day 17 of a cycle of therapy. No consistent hematopoietic, hepatic, or renal toxicity was observed. One partial response in a patient with colon carcinoma was seen and continues at more than eight months. Stable disease was observed in three patients with colon carcinoma, two patients with hypernephroma, one patient with pancreatic carcinoma, and one patient with melanoma. The predictability and reversibility of toxicity and the suggestion of antitumor activity in humans are observations which support the further evaluation of N-(phosphonacetyI)-L-aspartate in Phase II studies. Downloaded from cancerres.aacrjournals.org on February 9, 2016.

Original languageEnglish (US)
Pages (from-to)3992-3995
Number of pages4
JournalCancer research
Volume39
Issue number10
StatePublished - Oct 1 1979

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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