Clinical effects and pharmacokinetics of different dosage schedules of adriamycin.
Adriamycin was administered to 60 adults and 21 children by 3 different dosage schedules: 22.5 mg/sq m (0.6 mg/kg) daily for 4 days, 15 mg/sq m (0.4 mg/kg) every 8 hr for a total of 6 doses, and 50 to 120 mg/sq m as a single dose every 3 to 4 weeks. Objective responses lasting more than 1 month occurred in 5 subjects with acute leukemias or lymphoma, 3 with transitional cell carcinomas, 2 with sarcomas, 2 with Ewing's sarcoma and 1 each with bronchogenic carcinoma, orchidoblastoma, and thymoma. Toxic reactions included nausea, vomiting, stomatitis, alopecia, and hematopoietic depression, but significant cardiac toxicity occurred in only 1 patient. Pharmacokinetic data, collected in 25 patients by fluorometric and chromatographic assay, suggested a biphasic plasma clearance of drug with initial and secondary half-lives of about 1.5 and 14 to 21 hr, respectively. When drug was given every 8 hr there was evidence of loss of an initial very rapid phase of distribution of adriamycin and its metabolites. Urinary excretion accounted for 3.4 to 38.1% of administered fluorescence over a 72-hr period; in the first 24 hr, between 48.2 and 100% of this urinary material was in the form of adriamycin; leter, this fraction declined. No adriamycin or its fluorescent metabolites could be extracted from the stools.
D001773:Blood Cells / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D012509:Sarcoma / Q000188:drug therapy; D013280:Stomatitis / Q000139:chemically induced; D013945:Thymoma / Q000188:drug therapy
D004317:Doxorubicin