title: Combination of cytarabine and topotecan in patients treated for acute myeloid leukemia with persistent disease after frontline induction.
abstract: After a first course of induction chemotherapy, 30-40% of patients with acute myeloid leukemia (AML) do not achieve a complete response (CR). A second course of an anthracycline and intermediate-dose cytarabine (IDAC) allows a significant number of patients with persistent AML at day 14 to finally achieve a CR. We hypothesized that use of a topotecan and cytarabine combination in this setting might improve tolerance and efficacy. Cytarabine (1000 mg/m(2)/12 h days 1-4) was combined with topotecan (TA, 1.25 mg/m(2)/day by continuous intravenous infusion [CIV] days 1-4) in 31 consecutive patients with ≥ 5% marrow blasts by day 14 of induction. The median follow-up was 36 months. The CR rate was 81%, and the 2-year probability of overall survival and cumulative incidence of relapse were 66% and 38%, respectively. No unexpected toxicity was observed. Comparison with historical controls treated with the combination of a similar schedule of cytarabine and an anthracycline showed a better CR rate (p = 0.054), overall survival (p = 0.03) and cumulative incidence of relapse (p = 0.03). These results were confirmed in a multivariate analysis model. This work shows that the substitution of an anthracycline by topotecan is feasible and associated with significant efficacy for patients with AML with persistent leukemia at day 14 after standard-dose anthracycline induction.
authors.affiliation: Department of Hematology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prébet
authors.forename: Estelle
authors.initials: E
authors.lastname: Jean
authors.forename: Aurélie
authors.initials: A
authors.lastname: Autret
authors.forename: Aude
authors.initials: A
authors.lastname: Charbonnier
authors.forename: Jerome
authors.initials: J
authors.lastname: Rey
authors.forename: Anne
authors.initials: A
authors.lastname: Etienne
authors.forename: Evelyne
authors.initials: E
authors.lastname: D'incan
authors.forename: Sabine
authors.initials: S
authors.lastname: Fürst
authors.forename: Christine
authors.initials: C
authors.lastname: Arnoulet
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003561:Cytarabine; D019772:Topotecan