alanosine and Stomatitis

Topics: Adult; Aged; Alanine; Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Clinical Trials as Topic; Colonic Neoplasms; Female; Humans; Male; Middle Aged; Nausea; Phosphonoacetic Acid; Rectal Neoplasms; Stomatitis

Topics: Alanine; Carcinoma, Squamous Cell; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Leukopenia; Male; Stomatitis; Thrombocytopenia

L-alanosine (NSC 15353) is a newly developed antitumor antibiotic which acts as an inhibitor of purine intermediary metabolism. Experimental antitumor activity was demonstrated in a variety of murine neoplasms. A Phase I trial was undertaken on a daily x 5 (d x 5) schedule in 22 evaluable patients. Dose limiting toxicity was an oral mucositis characterized by beefy red oral, lingual and pharyngeal erythema. The maximum tolerated dose is 320 mg/m2/d x 5 every three weeks. The recommended dose for Phase II evaluation is 160 mg/m2/d x 5 every three weeks.

Topics: Adult; Aged; Alanine; Antibiotics, Antineoplastic; Drug Administration Schedule; Drug Evaluation; Female; Humans; Male; Middle Aged; Neoplasms; Stomatitis

Thirty patients with advanced metastatic colorectal adenocarcinoma were treated with alanosine at a dose of 160 mg/m2 daily for 5 days every 4 weeks. Sixteen patients had received no prior chemotherapy and 14 had been previously treated with one or more cytotoxic agents. No patient met the criteria for a complete or partial response. The major toxicity was stomatitis.

Topics: Adenocarcinoma; Adult; Aged; Alanine; Antibiotics, Antineoplastic; Colonic Neoplasms; Drug Evaluation; Female; Humans; Male; Middle Aged; Nausea; Rectal Neoplasms; Stomatitis

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.

Topics: Alanine; Aspartic Acid; Diarrhea; Digestive System Neoplasms; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Humans; Injections, Intravenous; Organophosphorus Compounds; Phosphonoacetic Acid; Stomatitis