Phase I and pharmacologic evaluation of nafazatrom in patients with cancer.
Nafazatrom was evaluated in escalating daily oral doses ranging from 0.25 to 8.0 g/m2 without producing significant toxicities. Malabsorption proved dose limiting at 8.0 g/m2 as a single daily dose, but splitting the same total dose into two or four doses circumvented this problem. Doses of 2.0 g/m2 at 6-h intervals or 4.0 g/m2 every 12 h are reasonable for Phase II and adjuvant trials. Pharmacologic evaluation of nafazatrom confirmed malabsorption at the highest single daily dose level tested and suggests that absorption was impaired in patients with extensive liver metastases.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000097:blood; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D047069:Pyrazolones
D000970:Antineoplastic Agents; D011720:Pyrazoles; D047069:Pyrazolones; D003545:Cysteine; C018845:nafazatrom