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/m(2) daily for 3 days together with ara-c 1 g/m(2) 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 x 10(9)/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/m(2) dose level, but minimal at 125 mg/m(2) (2 of 32, 6%) or 135 mg/m(2) (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.