Phase I clinical trial of mitozolomide.
Mitozolomide (NSC-353451; CCRG 81010; M and B 39565) is a novel potential anticancer agent that was selected for phase I study on the basis of broad spectrum activity in mouse tumors. Initially, mitozolomide was given iv as a short infusion to 37 patients in doses ranging from 8 to 153 mg/m2. Nausea and vomiting was dose-related but was not severe. The dose-limiting toxic effect was thrombocytopenia at doses greater than 115 mg/m2, and recovery from the thrombocytopenia was delayed up to 8 weeks. Partial responses were seen in two patients with adenocarcinoma of the ovary. The pharmacokinetics of mitozolomide showed that the half-life of the intact drug in the plasma was between 1 and 1.3 hours. The area under the curve was proportional to the dose administered. Mitozolomide is well-absorbed; therefore, future studies are recommended using a single-dose schedule orally or iv. In the phase I study reported here, a dose of 115 mg/m2 appeared to be safe, but additional studies have shown that when given orally to an older population, most patients experienced thrombocytopenia less than 50,000 cells/mm3. The recommended dose using current data is 90 mg/m2 iv or orally.
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001682:Biological Availability; D004341:Drug Evaluation; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C040369:mitozolomide