Phase I trial of 4-demethoxydaunorubicin (idarubicin) with single oral doses.
Twenty-four patients with a variety of solid tumors entered a Phase I trial with 4-demethoxydaunorubicin, a new analogue of daunorubicin. The drug was given as a single oral dose of 10-60 mg/m2 repeated every 3-4 weeks. Leukopenia was the dose-limiting toxicity. Other toxic effects included mild to moderate nausea and vomiting. Sixty mg/m2 was found to be the maximum tolerated dose in patients with fair tolerance to chemotherapy and normal liver function. Similar hematologic toxicity was reported in patients with very extensive prior chemotherapy or diffuse bone and/or liver metastases receiving 50 mg/m2. However, the wide range of the WBC nadirs reported with the same dose in 'good risk' cases, suggest that 40 mg/m2, increased up to 50 mg/m2 in the absence of significant myelotoxicity, could be more safely proposed as starting dose for Phase II trials. Pharmacokinetic studies were performed in five patients given a single dose of 40-60 mg/m2. IMI-30 (NSC 256439) appears to be rapidly absorbed and rapidly eliminated from plasma by means of a rapid and extensive biotransformation to 13-OH-idarubicin. The 13-dihydroderivative was present at higher and more prolonged levels than the parent compound, with an elimination half-life of about 40 hours.
D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D001682:Biological Availability; D001769:Blood / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D004341:Drug Evaluation; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D015255:Idarubicin; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D015255:Idarubicin; D003630:Daunorubicin