TY - JOUR
T1 - Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients
AU - Tassara, Michela
AU - Döhner, Konstanze
AU - Brossart, Peter
AU - Held, Gerhard
AU - Götze, Katharina
AU - Horst, Heinz A.
AU - Ringhoffer, Mark
AU - Köhne, Claus Henning
AU - Kremers, Stephan
AU - Raghavachar, Aruna
AU - Wulf, Gerald
AU - Kirchen, Heinz
AU - Nachbaur, David
AU - Derigs, Hans Gun̈ter
AU - Wattad, Mohammed
AU - Koller, Elisabeth
AU - Brugger, Wolfram
AU - Matzdorff, Axel
AU - Greil, Richard
AU - Heil, Gerhard
AU - Paschka, Peter
AU - Gaidzik, Verena I.
AU - Göttlicher, Martin
AU - Doḧner, Hartmut
AU - Schlenk, Richard F.
PY - 2014/6/26
Y1 - 2014/6/26
N2 - The outcome of patients with acute myeloid leukemia who are older than 60 years has remained poor because of unfavorable disease characteristics and patient-related factors. The randomized German-Austrian AML Study Group 06-04 protocol was designed on the basis of in vitro synergistic effects of valproic acid (VPA) and all-trans retinoic acid with chemotherapy. Between 2004 and 2006, 186 patients were randomly assigned to receive 2 induction cycles with idarubicin, cytarabine, and all-trans retinoic acid either with VPA or without (STANDARD). In all patients, consolidation therapy was intended. Complete remission rates after induction tended to be lower in VPA compared with STANDARD (40% vs 52%; P 5 .14) as a result of a higher early death rate (26% vs 14%; P 5 .06). The main toxicities attributed to VPA were delayed hematologic recovery and grade 3/4 infections, observed predominantly during the second induction cycle. After restricting VPA to the first induction cycle and reducing the dose of idarubicin, these toxicities dropped to rates observed in STANDARD. After a median follow-up time of 84 months, event-free and overall survivalwere not different between the 2 groups (P 5 .95 andP5.57, respectively). However, relapse-free-survival was significantly superior in VPAcompared with STANDARD(24.4% vs 6.4% at 5 years; P 5 .02). Explorative subset analyses revealed that AML with mutated Nucleophosmin 1 (NPM1) may particularly benefit from VPA. This trial was registered at www.clinicaltrials.gov as #NCT00151255.
AB - The outcome of patients with acute myeloid leukemia who are older than 60 years has remained poor because of unfavorable disease characteristics and patient-related factors. The randomized German-Austrian AML Study Group 06-04 protocol was designed on the basis of in vitro synergistic effects of valproic acid (VPA) and all-trans retinoic acid with chemotherapy. Between 2004 and 2006, 186 patients were randomly assigned to receive 2 induction cycles with idarubicin, cytarabine, and all-trans retinoic acid either with VPA or without (STANDARD). In all patients, consolidation therapy was intended. Complete remission rates after induction tended to be lower in VPA compared with STANDARD (40% vs 52%; P 5 .14) as a result of a higher early death rate (26% vs 14%; P 5 .06). The main toxicities attributed to VPA were delayed hematologic recovery and grade 3/4 infections, observed predominantly during the second induction cycle. After restricting VPA to the first induction cycle and reducing the dose of idarubicin, these toxicities dropped to rates observed in STANDARD. After a median follow-up time of 84 months, event-free and overall survivalwere not different between the 2 groups (P 5 .95 andP5.57, respectively). However, relapse-free-survival was significantly superior in VPAcompared with STANDARD(24.4% vs 6.4% at 5 years; P 5 .02). Explorative subset analyses revealed that AML with mutated Nucleophosmin 1 (NPM1) may particularly benefit from VPA. This trial was registered at www.clinicaltrials.gov as #NCT00151255.
UR - http://www.scopus.com/inward/record.url?scp=84903624892&partnerID=8YFLogxK
U2 - 10.1182/blood-2013-12-546283
DO - 10.1182/blood-2013-12-546283
M3 - Article
C2 - 24797300
AN - SCOPUS:84903624892
SN - 0006-4971
VL - 123
SP - 4027
EP - 4036
JO - Blood
JF - Blood
IS - 26
ER -