title: 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/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.
authors.affiliation: Department of Leukemia, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA. jcortes@mdanderson.org
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.forename: E
authors.initials: E
authors.lastname: Estey
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: F
authors.initials: F
authors.lastname: Giles
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: C
authors.initials: C
authors.lastname: Koller
authors.forename: M
authors.initials: M
authors.lastname: Beran
authors.forename: D
authors.initials: D
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Keating
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: 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
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D003561:Cytarabine; D003630:Daunorubicin