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A Phase I study of the combination N‐(phosphonacetyl)‐L‐aspartate (PALA, NSC‐224131) and L‐alanosine (NSC‐153353) in patients with advanced cancer
Author(s) -
Creagan Edward T.,
O'Connell MICHAEL J.,
Kovach John S.
Publication year - 1983
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19830815)52:4<615::aid-cncr2820520407>3.0.co;2-o
Subject(s) - medicine
This article reports a Phase I study of combined therapy with N‐(phosphonacetyl)‐L‐aspartate (PALA) and L‐alanosine in 26 patients with advanced cancer. Each agent exhibits antitumor effect by enzyme inhibition: PALA blocks pyrimidine biosynthesis by impeding aspartate transcarbamylase and L‐alanosine depletes purine nucleotides by interfering with adenylosuccinate synthetase. These agents were selected for clinical investigation in light of synergistic cytotoxicity in vitro against human tumor cell lines and in vivo against P‐388 murine leukemia resistant to cytosine arabinoside. Dose‐limiting toxicities were stomatitis and diarrhea to a lesser extent. There was no substantial myelosuppression. The authors recommend either of two intravenous regimens for studies of therapeutic activity in selected patients with neoplastic diseases: a one‐day treatment repeated of PALA, 5.0 g/m 2 and L‐alanosine, 3.0 g/m 2 , repeated every 3 weeks; or a monthly program of PALA, 500 mg/m 2 /d 1–5 and L‐alanosine, 60 mg/m 2 /d 1‐5.