Phase I trial of aclacinomycin-A. A clinical and pharmacokinetic study.
Aclacinomycin-A is a new anthracycline antibiotic with a broad spectrum of antitumor activity in animals. Compared to doxorubicin, it was found to produce less cardiotoxicity and alopecia. A Phase I trial of aclacinomycin-A given as a weekly 15 min IV infusion was conducted in 20 previously treated patients with advanced solid tumors. Four dose levels ranging from 40 to 100 mg/m2 were studied; myelotoxicity was dose-limiting at 85 and 100 mg/m2. Other toxicities were moderate to severe nausea and vomiting in 9 patients, mild phlebitis in 2 patients, and mild abnormality of liver function tests in 3 patients. No cardiac or renal toxicities were seen, but two partial responses were observed. The pharmacokinetic profile of aclacinomycin-A in plasma and urine was studied in 3 patients given 65 mg/m2 using a high performance liquid chromatography assay. The data obtained were consistent with a two compartment model of drug disposition with initial and terminal half-life values of 6.6 min and 13.3 h, respectively. The major fluorescent metabolite was eliminated with a terminal half-life of 25 h. Two metabolites as well as the parent drug were excreted in the urine as less than 10% of the doses given. This pharmacokinetic profile is similar to that of other anthracyclines, although aclacinomycin-A appears to have lower blood levels than doxorubicin given at equivalent doses. On this weekly schedule, the recommended dose is 65 mg/m2 for Phase II trials.
D015250:Aclarubicin; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009279:Naphthacenes / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D015250:Aclarubicin