ATTENUATED-DOSE IDARUBICIN IN ACUTE MYELOID-LEUKEMIA OF THE ELDERLY -PHARMACOKINETIC STUDY AND CLINICAL-RESULTS

AML in the elderly is characterized by intrinsic biological features i mplying an enhanced chemoresistance. Intensive chemotherapy should be the treatment of choice, but the standard doses could induce unaccepta ble rates of aplastic deaths. We evaluated the efficacy of an inductio n protocol with attenuated-dose idarubicin (IDA) 8 mg/m(2) for 3 d plu s cytarabine and etoposide in 26 AML patients aged >60. 18 patients (6 9%) achieved CR, five (19%) were nonresponders and three (12%) died du ring induction. To compare the pharmacokinetics of IDA between elderly and young patients, we assayed daily the serum level of the drug and of its metabolite (idarubicinol, IDAol) in a group of eight elderly pa tients who received a dose of 8 mg/m(2) (group A) and in a group of ni ne younger AML patients treated with 12 mg/m(2) (group B). The apparen t terminal half-life of IDAol was significantly longer in the elderly than in the younger patients (mean half-life 59.7 h versus 41.4 h, P < 0.05). The values of the area under the serum concentration curve of IDAol indicated that the two patient groups received a very similar ex posure to the drug despite the different doses. In conclusion, this pr otocol, based on attenuated doses of IDA, compares well with the resul ts obtained previously in similar age-matched patient series.