High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia.
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.
Cortes
J
J
Department of Leukemia, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA. jcortes@mdanderson.org
Estey
E
E
O'Brien
S
S
Giles
F
F
Shen
Y
Y
Koller
C
C
Beran
M
M
Thomas
D
D
Keating
M
M
Kantarjian
H
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004337:Drug Carriers; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008081:Liposomes; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome
D004337:Drug Carriers; D008081:Liposomes; D003561:Cytarabine; D003630:Daunorubicin