A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML.
Publication Title
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Document Type
Article
Publication Date
1-1-2024
Keywords
washington; swedish; swedish cancer; Humans; Cytarabine; Vorinostat; Leukemia, Myeloid, Acute; Daunorubicin; Idarubicin; Remission Induction; Antineoplastic Combined Chemotherapy Protocols
Abstract
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.).
Clinical Institute
Cancer
Specialty/Research Institute
Oncology
DOI
10.1038/s41375-023-02073-x
