Phase II evaluation of N-(phosphonacetyl)-L-aspartic acid (PALA) in patients with non-small cell carcinoma of the lung

E. S. Casper, Richard J. Gralla, D. P. Kelsen, A. Houghton, R. B. Golbey, C. W. Young

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Asparate transcarbamylase catalyzes a key reaction in the pathway of pyrimidine biosynthesis, the condensation of carbamyl phosphate with aspartic acid, generating carbamyl-L-aspartate. N-(Phosphonacetyl)-L-aspartic acid (PALA), a stable analog of the transition state in that reaction, is a potent inhibitor of asparate transcarbamylase. PALA has demonstrateed antitumor activity in both Lewis lung carcinoma and B16 melanoma, two solid tumor models resistant to other antimetabolites. Phase I studies have shown that PALA given at a weekly dose of 4.5 g/m 2 is nonmyelosuppressive and produces moderate, but manageable, gastrointestinal and cutaneous toxicity. Most of the drug is excreted unmetabolized in the urine. Because of its unique site of action, its activity in resistant solid tumor models, and its lack of myelotoxicity, a phase II study of PALA in non-small cell lung cancer was initiated.

Original languageEnglish (US)
Pages (from-to)705-707
Number of pages3
JournalCancer Treatment Reports
Volume64
Issue number4-5
StatePublished - 1980
Externally publishedYes

Fingerprint

Aspartic Acid
Non-Small Cell Lung Carcinoma
Carbamyl Phosphate
Lewis Lung Carcinoma
Antimetabolites
Experimental Melanomas
Neoplasms
Urine
Skin
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Casper, E. S., Gralla, R. J., Kelsen, D. P., Houghton, A., Golbey, R. B., & Young, C. W. (1980). Phase II evaluation of N-(phosphonacetyl)-L-aspartic acid (PALA) in patients with non-small cell carcinoma of the lung. Cancer Treatment Reports, 64(4-5), 705-707.

Phase II evaluation of N-(phosphonacetyl)-L-aspartic acid (PALA) in patients with non-small cell carcinoma of the lung. / Casper, E. S.; Gralla, Richard J.; Kelsen, D. P.; Houghton, A.; Golbey, R. B.; Young, C. W.

In: Cancer Treatment Reports, Vol. 64, No. 4-5, 1980, p. 705-707.

Research output: Contribution to journalArticle

Casper, ES, Gralla, RJ, Kelsen, DP, Houghton, A, Golbey, RB & Young, CW 1980, 'Phase II evaluation of N-(phosphonacetyl)-L-aspartic acid (PALA) in patients with non-small cell carcinoma of the lung', Cancer Treatment Reports, vol. 64, no. 4-5, pp. 705-707.
Casper, E. S. ; Gralla, Richard J. ; Kelsen, D. P. ; Houghton, A. ; Golbey, R. B. ; Young, C. W. / Phase II evaluation of N-(phosphonacetyl)-L-aspartic acid (PALA) in patients with non-small cell carcinoma of the lung. In: Cancer Treatment Reports. 1980 ; Vol. 64, No. 4-5. pp. 705-707.
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