Phase I trial of aclacinomycin A.
Aclacinomycin A (ACM-A), an anthracycline analog, was given to 17 patients with solid tumors and to one patient with multiple myeloma, in a phase I clinical trial. A single dose of 60-120 mg/m2 was given every 3 weeks. Dose-limiting toxicity was myelosuppression, especially thrombocytopenia. Granulocytopenia was variable and did not always recover by Day 21 in time for the next ACM-A treatment. Other toxic effects were nausea, vomiting, urticaria, and elevation of hepatic enzymes. Alopecia was not a side effect, even in patients receiving multiple courses of ACM-A. Nine patients were monitored with 24-hour continuous ECG recordings (Holter) on 19 ACM-A treatment days. The incidence of premature atrial and ventricular beats was significantly increased following ACM-A administration. In addition, one patient developed episodes of high-degree atrioventricular block and complete heart block after each of four ACM-A doses, necessitating the insertion of a pacemaker. No antitumor responses were seen in the ten patients who had measurable disease and who had received two or more courses of ACM-A. The recommended doses for solid tumor phase II studies are 100 mg/m2 as a single dose every 4 weeks for patients with high performance status and minimal prior chemotherapy and 60 mg/m2 every 4 weeks for all other patients. Until the acute cardiac effects of ACM-A are further understood, we recommend that all patients receiving ACM-A be monitored by ECG recordings.
D015250:Aclarubicin; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001773:Blood Cells / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009279:Naphthacenes / Q000009:adverse effects / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D015250:Aclarubicin