Clinical and clinical pharmacologic studies of 2-amino-1,3,4-thiadiazole (A-TDA:NSC 4728).
A clinical phase I-II evaluation of 2-amino-1,3,4-thiadiazole (A-TDA) administered daily, twice a week, or weekly was undertaken, in which 71 patients were treated with a range of doses from 2 mg/m2 to 200 mg/m2. Pharmacokinetic studies employing high-performance liquid chromatography (HPLC) demonstrated a terminal (beta) serum half-life of 2.19 h. Stomatitis, dermatitis, nausea, vomiting, and lethargy were observed. No significant leukopenia or thrombocytopenia, however, was noted. A-TDA administration led to hyperuricemia, which was adequately controlled with concurrent administration of allopurinol. Antitumor responses included one partial response in a patient with large cell carcinoma of the lung and three objective responses (2 non-small cell lung and 1 squamous cell carcinoma of the esophagus). Two patients with adenocarcinoma of the lung had a marked improvement of psoriasis during A-TDA therapy. Further phase II studies in patients with cancer and trials in patients with psoriasis are recommended.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D003875:Drug Eruptions / Q000209:etiology; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D013280:Stomatitis / Q000139:chemically induced; D013830:Thiadiazoles / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D014527:Uric Acid / Q000097:blood
D000970:Antineoplastic Agents; D013830:Thiadiazoles; D014527:Uric Acid; C010852:2-amino-1,3,4-thiadiazole