Oral idarubicin in patients with late chronic phase chronic myelogenous leukemia or chronic myelomonocytic leukemia

Patients with chronic myelogenous leukemia (CML) who have failed or cannot receive interferon alpha (IFN-alpha) based regimens or patients with advanc ed chronic myelomonocytic leukemia (CMML) have very limited current therape utic options. Hence, there is a need to develop new strategies for these pa tients. This study was undertaken to determine the efficacy and toxicity of a chronic low-dose oral idarubicin regimen in these patients as positive d ata has been generated on this agent in shorter schedules given to patients with other hematological malignancies. Eighteen patients were treated on s tudy. The starting dose of oral idarubicin was 2 to 5 mg/m(2) daily dependi ng in initial WBC count. This dose was escalated in the absence of Grade 4 myelosuppression or Grade 3 or 4 extramedullary toxicity. Oral idarubicin w as given daily for 28 days followed by a 21 day break off treatment in repe ated cycles until there was evidence of disease progression or intolerable toxicity. The dose of idarubicin was adjusted, at 2-week intervals, by 25% to maintain a white blood cell (WBC) count between 2 and 4x10(9)/L and a pl atelet count of >75x10(9)/L. The dose was reduced by 25% for grade 2 extram edullary toxicity and held until toxicity resolved to grade 2 or better for grade 3 toxicity. Oral idarubicin was then restarted at 75% of the initial dose. Five out of 14 CML patients achieved a complete hematologic remission. No C MML patient responded (median survival 3 months). The overall median surviv al was 24 months. CML patients had a median survival of 28 months. Major to xicities (myelosuppression, gastrointestinal, cardiac) were infrequent with a median cumulative dose of 1110mg/m(2) (range 54-9750). Five patients hav e received oral idarubicin for > 1 year with no overt cardiotoxicity, reach ing median cumulative dose of 2756 mg/m(2) (range 2550-9750) which is highe r than those documented in prior studies. We conclude that Oral idarubicin is sufficiently safe and active to warrant phase II studies investigating i t as part of interferon-based regimens in patients with advanced CML.