Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0038362 (
stomatitis
)
8,852
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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/m2 and L-alanosine, 3.0 g/m2, repeated every 3 weeks; or a monthly program of PALA, 500 mg/m2/d 1-5 and L-alanosine, 60 mg/m2/d 1-5.
...
PMID:A Phase I study of the combination N-(phosphonacetyl)-L-aspartate (PALA, NSC-224131) and L-alanosine (NSC-153353) in patients with advanced cancer. 686 Oct 99