title: All trans retinoic acid in combination with intermediate-dose cytarabine and idarubicin in patients with relapsed or refractory non promyelocytic acute myeloid leukemia: a phase II randomized trial.
abstract: BACKGROUND
  All trans retinoic acid has shown a remarkable effectiveness in acute promyelocytic leukemia. These results have encouraged studies of treatment with ATRA in other acute myeloid leukemia subtypes.
  
  
  METHODS
  In order to evaluate toxicity and antileukemic efficacy of all ATRA in patients with relapsed or refractory non promyelocytic AML, 95 patients (median age, 58 years; range, 20 to 80 years), with unclassified AML according to the FAB classification or secondary AML at diagnosis, or refractory or relapsing AML, received induction therapy with Idarubicin, 10 mg/m(2)/day, for 3 days and cytarabine, 1000 mg/m(2)/12 h, for 6 days, alone or combined, on a randomized basis, with ATRA, 45 mg/m(2)/day, from day 1 to complete remission. Patients in CR received maintenance therapy with 6 monthly courses combining Ida, 10 mg/m(2)/day, intravenously, on day 1 with Ara-C100 mg/m(2)/day, subcutaneously, from day 1 to day 5.
  
  
  RESULTS
  Results were evaluated after one induction course. Overall 54 patients (57%, 26 with ATRA and 28 without ATRA) achieved CR including five patients treated at time of initial diagnosis, seven previously resistant, 38 in first relapse and four in further relapse. Thirty patients (31%) had resistant disease and 11 (12%) died from toxicity. Median time for neutrophil recovery to 0.5 x 10(9)/l and platelets to 20 x 10(9)/l was 31 and 21 days respectively. Severe toxicity (WHO grade >or=3) included infections (37%), diarrhea (9%), bleeding (3%), vomiting (16%), hyperbilirubinemia (5%), mucositis (6%) and hypercreatininemia (2%). No ATRA syndrome was noted in the ATRA arm. Median overall survival for the entire cohort was 6.3 months and median disease-free survival was 4.7 months. There were no statistical differences in terms of CR, DFS, and OS between the two arms.
  
  
  CONCLUSIONS
  We conclude that ATRA in combination with Ida and Ara-C can be administered safely to high-risk AML patients. However, in this setting, ATRA did not offer any advantage when compared to chemotherapy alone.
authors.affiliation: Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Amine
authors.initials: A
authors.lastname: Belhabri
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Eric
authors.initials: E
authors.lastname: Wattel
authors.forename: Youcef
authors.initials: Y
authors.lastname: Chelghoum
authors.forename: Bruno
authors.initials: B
authors.lastname: Anglaret
authors.forename: Anne
authors.initials: A
authors.lastname: Vekhoff
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhedin
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Denis
authors.initials: D
authors.lastname: Fière
authors.forename: Eric
authors.initials: E
authors.lastname: Archimbaud
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016879:Salvage Therapy; D016019:Survival Analysis; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D003561:Cytarabine; D014212:Tretinoin; D015255:Idarubicin