Phase I-II study of aclacinomycin for a treatment of acute myeloid leukemia.

Aclacinomycin A (ACM) was administered for induction treatment to 40 previously treated acute myeloid leukemia (AML) patients. 38 patients aged 2 to 80 years (mean +/- SE, 35.0 +/- 3.2 years) with overt AML were evaluated; of these, seventeen patients were given ACM after an unsuccessful attempt to obtain a complete remission (CR) with various regimens comprising adriamycin (ADM) or daunorubicin (DNR) and were considered resistant to these drugs. Thirteen patients received ACM at a daily dose of 10 to 30 mg/m2 IV bolus until the maximum total dose of 300 mg/m2 per course was reached or until unacceptable toxicity appeared; of these patients, 2 (15%) attained a CR. Twenty-five patients were given 10-day courses of ACM at the daily dose of 15 mg/m2 IV bolus with 10-day intervals between courses; with this regimen 11 patients (44%) attained a CR. The overall CR rate was 34%. Total doses necessary to attain a CR ranged from 150 to 600 mg/m2. CR was attained by 6 patients (35%) of the 17 who were previously resistant to ADM or DNR. The incidence and severity of the toxic effects such as mucositis, diarrhea, vomiting and infection were related to the dose of ACM administered during each course of therapy. However, in patients who received 150 mg/m2 per course the toxicity was within acceptable limits. Alopecia was not observed. Transient T-wave inversion was observed in 3 patients and atrial flutter developed in one patient. Therefore, we conclude that ACM is a new major drug in the treatment of AML.