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Among younger patients with previously untreated acute myeloid leukemia (AML), standard-dose cytarabine appears to be less toxic than high-dose treatment, with or without vorinostat, according to research published in Leukemia.
Although clinicians must account for patient and disease characteristics when making treatment decisions in the AML space, the most common induction regimen relies at least in part on cytarabine and anthracycline. Younger, fit patients may tolerate more aggressive regimens, but relapse rates remain high.
It is also unclear whether patients are likely to benefit from a higher dose of cytarabine in the induction phase; there is also some evidence that vorinostat, a histone deacetylase inhibitor, may improve clinical outcomes.
For the randomized phase 3 S1203 trial (ClinicalTrials.gov Identifier: NCT01802333), researchers evaluated whether high-dose cytarabine, with or without vorinostat, is superior to standard-dose cytarabine among patients with previously untreated AML.
Overall, 738 patients were enrolled and randomly assigned to 1 of 3 treatment arms: daunorubicin and cytarabine (DA; 261 patients), idarubicin with higher dose cytarabine (IA; 261 patients), and IA with vorinostat (IA + V; 216 patients). In the overall cohort, at baseline, the average age was 49 years, 51% of patients were male, 87% of patients had a performance status of 0 or 1, and 13%, 63%, and 22% of patients had favorable, intermediate, and unfavorable cytogenetics, respectively.
The median follow-up among patients without events was 33 months. At this point, there was no difference in event-free survival rates in the DA, IA, or IA + V arms.
In the overall cohort, the remission rate was 77.5%; the complete response rate was 62.5%. No differences in remission rates or overall survival rates were observed.
Among patients with favorable cytogenetics, however, patients in the DA group followed by post-remission high-dose cytarabine appeared to have improved event-free, but not overall, survival.
Furthermore, patients in the IA and IA + V arms had a trend towards higher toxicity rates compared with those in the DA arm. Patients in the IA + V arm had higher rates of both grade 3 diarrhea and typhlitis than did patients in the IA and DA 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,” the authors wrote in their report.
Reference
Garcia-Manero G, Podoltsev NA, Othus M, et al. A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML. Leukemia. Published online November 7, 2023. doi:10.1038/s41375-023-02073-x
This article originally appeared on Hematology Advisor
