title: 4-demethoxydaunorubicin (idarubicin) in combination with 1-beta-D-arabinofuranosylcytosine in the treatment of relapsed or refractory acute leukemia.
abstract: We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: E
authors.initials: E
authors.lastname: Berman
authors.forename: V
authors.initials: V
authors.lastname: Raymond
authors.forename: A
authors.initials: A
authors.lastname: Daghestani
authors.forename: Z A
authors.initials: ZA
authors.lastname: Arlin
authors.forename: T S
authors.initials: TS
authors.lastname: Gee
authors.forename: S
authors.initials: S
authors.lastname: Kempin
authors.forename: C
authors.initials: C
authors.lastname: Hancock
authors.forename: L
authors.initials: L
authors.lastname: Williams
authors.forename: Y W
authors.initials: YW
authors.lastname: Stevens
authors.forename: B D
authors.initials: BD
authors.lastname: Clarkson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000493:pharmacokinetics; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D003561:Cytarabine; D015255:Idarubicin