Phase I trial of mitoxantrone by 24-hour continuous infusion.
Mitoxantrone (DAD) is a new agent which intercalates into DNA. Preclinical studies have demonstrated activity equal to or greater than that of doxorubicin in all tumor systems tested. In this phase I clinical trial, the schedule of drug administration consisted of a 24-hour continuous iv infusion repeated at 21-day intervals. Twenty-nine patients received a total of 66 courses over a dose range of 4-15 mg/m2. The dose-limiting toxic effect was leukopenia, with a wbc count nadir on Day 12 and resolution prior to Day 21. Other toxic effects were thrombocytopenia, mild phlebitis, and blue discoloration of veins. Objective tumor responses were seen in a patient with adenocarcinoma of the breast and in another patient with clear cell carcinoma of the vagina. An additional six patients with acute leukemia were treated at a dose of 12 mg/m2; a decrease in peripheral blast count was observed in four of these six patients. The toxicity of DAD by 24-hour iv infusion was similar to that previously reported for iv bolus administration. We recommend phase II evaluation of DAD at a dose of 12 mg/m2 by single iv injection at 21-day intervals. Patients with acute leukemia should be evaluated at higher dose levels.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000880:Anthraquinones / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D006801:Humans; D007223:Infant; D007263:Infusions, Parenteral; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D008942:Mitoxantrone; D009369:Neoplasms / Q000188:drug therapy*
D000880:Anthraquinones; D000970:Antineoplastic Agents; D008942:Mitoxantrone