PHASE-I-II STUDY OF ACLARUBICIN FOR TREATMENT OF ACUTE MYELOID-LEUKEMIA

  • 1 January 1984
    • journal article
    • research article
    • Vol. 68  (6) , 881-886
Abstract
Aclarubicin (ACM) was administered as induction treatment to 40 patients with acute myeloid leukemia (AML) who were refractory to initial induction chemotherapy or in relapse. Thirty-eight patients with AML, 2-80 yr of age (mean .+-. SE, 35.0 .+-. 3.2), were evaluated during this study. Seventeen of these patients were given ACM after an unsuccessful attempt had been made to attain a complete remission (CR) with various regimens that included doxorubicin or daunorubicin; this group was considered resistant to these drugs. ACM was administered by rapid i.v. injection. Thirteen patients received a single course of ACM at a daily dose of 10-30 mg/m2 until a maximum total dose of 300 mg/m2 was reached or until unacceptable toxicity appeared. Of these patients, 2 (15%) attained a CR. The other 25 patients were given 10-day courses of ACM at a daily dose of 15 mg/m2 with 10-day intervals between courses; courses were repeated until the blast cells were cleared from peripheral blood and bone marrow or until progressive disease became evident. With this regimen, 11 patients (44%) attained a CR. The overall CR rate for the 38 patients was 34%. Total doses necessary to achieve a CR ranged from 150-600 mg/m2. A CR was attained by 6 patients who were previously resistant to a regimen containing moderate doses of doxorubicin. The incidence and severity of the toxic effects were related to the dose of ACM administered per course of therapy. The incidence of mucositis, diarrhea, vomiting and infection in patients who received doses > 150 mg/m2 per course was significantly higher than that observed in patients who received a dose of 150 mg/m2 per course. In the latter patients, toxicity was within acceptable limits. Alopecia was not observed. Three patients had transient T-wave inversion; reversible atrial flutter developed in 1 patient. ACM apparently is a major new drug for the treatment of AML.