Stewart J A, Ackerly C C, Myers C F, Newman R A, Krakoff I H
Cancer Chemother Pharmacol. 1986;16(3):287-91. doi: 10.1007/BF00293994.
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.
对2-氨基-1,3,4-噻二唑（A-TDA）进行了临床I-II期评估，给药方式为每日、每周两次或每周一次，71例患者接受了2mg/m²至200mg/m²不等剂量的治疗。采用高效液相色谱法（HPLC）进行的药代动力学研究表明，终末（β）血清半衰期为2.19小时。观察到口腔炎、皮炎、恶心、呕吐和嗜睡。然而，未发现明显的白细胞减少或血小板减少。给予A-TDA导致高尿酸血症，通过同时给予别嘌呤醇可得到充分控制。抗肿瘤反应包括1例肺大细胞癌患者出现部分缓解，以及3例客观反应（2例非小细胞肺癌和1例食管鳞状细胞癌）。2例肺腺癌患者在A-TDA治疗期间银屑病有明显改善。建议对癌症患者进一步开展II期研究，并对银屑病患者进行试验。
