68 O - Maintenance low-dose (LD) oral idarubicin (oIDA) in elderly patients (pts) with acute myelogeneous leukemia (AML)

Abstract

IDA by i.v. route. especially in combination with cytosine arabinoside (Ara-C). proved quite effective for intensive chemotherapy of AML However, persisting controversies on aggressive/intensive versus “ottenvated” regimens for elderly AML pts emphasize the interest of olDA in this latter setting (ct M.R. Howard et al and M.J. Keating. Clin. Drug Invest. 1995; 9. Suppl. 2: 16–38) A 69% complete response (CR) rate was recentty reported (F. Leoni et al Br. J. Hoematol 1995; 90: 169–174) among 25 elderly AML pts (> 60 yrs old) with an “attenuated” dose of IDA, i.e. 8 mg/m2 i.v. d, 1. 3, and 5. plus Ara-C 200 mg/m2 by continuous i.v. infusion (ClV) d, 1–7, and etoposide (VP-16) 60 mg/m2 i.v. d, 1–5. The areas under the curve (AUS) of plasma concentrations/time of both unchanged IDA and of its uniquely active 13-OH metabolite, Idarubicinol (IDAol). in a group of 8 elder1y recipients of IDA 8 mg/m2 were closely comparable to those recorded in 9 younger AML pts trealed with standard-dose IDA (12 mg/m2). Importantty, due to first-pass liver metabolism. the yield of IDAol with olDA is about twofold that achieved with i.v. administration. We (Musso et al., Eur. J. Cancer 1994; 30. Suppl. 1: 537) reported 4 CR and 4 CR out of 11 evaluable elderly (age ronge 67 to 81 years) AML pts with on “attenuated” regimen of olDA 20 mg/m2 daily d. 1–3 q 3–4 wks. Subsequently, based on the assumption that sustained. chronic exposure to LD-oIDA could control minimal residual disease (MRD), possibly via cell-differentiating and/or apoptogenic stimuli. we enrolled ten previous responders to standard induction chemotherapy for AML (IDA 8 mg/m2 i.v. d. 1–3. YP-16 100 mg/m2 d. 1–3 i.v., and Ara-C 100 mg/m2 d. 1–5 CIV) to receive maintenance olDA 5 mg doily d. 1–14 at 2-wk: intervals for at least 6 months. Long-term LD-olDA was well tolerated. Dose-limiting myelosuppression was modest. with leukocyte (WBC) and platelet (PLT) nadirs ≥ 500 and 50,000x 109/1, respectively, and without ony infectious complications. Nonhemotological toxicities were also acceptable: nausea/vomiting easily managed. no recorded diarrhea or mucositis. The convenience or oral administration contributed to excellent compliance. Plasmo IDA and IDAol were monitored during the lreatment. In conclusion. long-term LD-oIDA would appear valuable as a maintenance regimen.