High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia

Abstract

BACKGROUND Liposomal encapsulation of daunorubicin (DaunoXome, DNX; Nexstar Pharmaceutical, Boulder, CO) changes the pharmacology profile to increase delivery to tumor sites and decrease toxicity. The authors investigated the effect of daunorubicin in combination with ara‐C in patients with refractory or recurring acute myelogenous leukemia (AML). PATIENTS AND METHODS Sixty‐two patients with refractory or recurring AML received escalating doses of daunorubicin of 75, 100, 125, or 135 mg/m² daily for 3 days together with ara‐C 1 g/m² intravenous continuous infusion daily for 4 days. RESULTS Eighteen patients (29%) achieved a complete remission (CR) and 7 (11%) a hematologic improvement (i.e., met all criteria for CR except for platelet count < 100 × 10⁹/L) for an overall response rate of 40%. The dose‐limiting toxicity was mucositis in 4 in 9 (44%) patients treated at the 150 mg/m² dose level, but minimal at 125 mg/m² (2 of 32, 6%) or 135 mg/m² (1 of 13, 8%). Cardiotoxicity Grade 2 was observed in 4 patients (6%) and Grade 3 or higher in 4 patients (6%). The median CR duration was 63 weeks, and overall survival rate was 25 weeks, with 28% patients alive after 1 year. CONCLUSIONS The combination of DNX (or liposomal daunorubicin) and ara‐C has significant antileukemia activity with acceptable toxicity. Further studies are warranted to investigate the role of high‐dose anthracyclines in frontline AML therapy. Cancer 2001;92:7–14. © 2001 American Cancer Society.