A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML.

Autor: Garcia-Manero G; Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA., Podoltsev NA; Yale School of Medicine, New Haven, CT, USA. nikolai.podoltsev@yale.edu., Othus M; SWOG Statistics and Data Management Center, Seattle, WA, USA., Pagel JM; Swedish Cancer Institute, Seattle, WA, USA., Radich JP; Fred Hutchinson Cancer Center, Seattle, WA, USA., Fang M; Fred Hutchinson Cancer Center, Seattle, WA, USA., Rizzieri DA; Duke University Medical Center, Durham, NC, USA., Marcucci G; Ohio State University (Alliance), Columbus, OH, USA.; City of Hope, Duarte, CA, USA., Strickland SA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.; Sarah Cannon, Nashville, TN, USA., Litzow MR; Mayo Clinic, Rochester, MN, USA., Savoie ML; Tom Baker Cancer Centre, Calgary, AB, Canada., Medeiros BC; Stanford University, Stanford, CA, USA., Sekeres MA; Cleveland Clinic, Cleveland, OH, USA.; University of Miami, Maiami, FL, USA., Lin TL; University of Kansas Medical Center, Kansas City, KS, USA., Uy GL; Washington University School of Medicine, St. Louis, USA., Powell BL; Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, USA., Kolitz JE; North Shore University Hospital, Manhasset, NY, USA., Larson RA; University of Chicago, Chicago, IL, USA., Stone RM; Dana Farber Cancer Institute, Boston, MA, USA., Claxton D; Pennsylvania State Milton S Hershey Medical Center, Hummelstown, USA., Essell J; Jewish Hospital, Cincinnati, OH, USA., Luger SM; University of Pennsylvania Abramson Cancer Center, Philadelphia, PA, USA., Mohan SR; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.; Sarah Cannon, Nashville, TN, USA., Moseley A; SWOG Statistics and Data Management Center, Seattle, WA, USA., Appelbaum FR; Fred Hutchinson Cancer Center, Seattle, WA, USA., Erba HP; Duke University Cancer Center, Durham, NC, USA.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Jan; Vol. 38 (1), pp. 58-66. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1038/s41375-023-02073-x
Abstrakt: Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 were NPM1 and 158 FLT3 mutated. The overall remission rate was 77.5% including 62.5% CR and 15.0% CRi. No differences in remission, EFS, or overall survival were observed among the 3 arms except for the favorable cytogenetics subset who had improved outcomes with DA and postremission high dose cytarabine. A trend towards increased toxicity was observed with the IA and IA + V arms. The use of higher dose cytarabine during induction therapy in younger patients with AML, with or without vorinostat, does not result in improved outcomes. (Funded by the US National Institutes of Health and others, ClinicalTrials.gov number, NCT01802333.).
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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