Coadministration with entinostat – a cell-cycle inhibitor – appears to decrease hematologic responsiveness to azacitidine treatment for high-risk myelodysplastic syndrome, according to data from an open-label, phase II randomized trial.
An earlier, phase I pilot study had suggested that the combination was effective and tolerable, however this phase II study in 149 patients (97 patients with myelodysplastic syndrome and 52 patients with acute myeloid leukemia) showed a lower overall hematologic response and lower median overall survival in the combination arm, compared with the azacitidine-only arm, said Dr. Thomas Prebet, who was at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, when the work was done, but is now at Institut Paoli Calmettes, Marseille, France, and his colleagues.
They also performed genome-wide methylation studies on 99 specimens, finding that while demethylation in the combination arm was trending toward overall demethylation, it was significantly reduced, compared with the single agent arm, suggesting the entinostat was actually blocking the action of the azacitidine (J. Clin. Oncol. 2014 March 24 [doi:10.1200/JCO.2013.50.3102]).
The authors did note that the lower-dose, 10-day schedule of azacitidine, which was developed specifically for this phase II trial, appeared to double the rate of hematologic normalization, compared with that observed in a previous study using the standard 7-day schedule, suggesting that the longer schedule was more effective.
Some authors reported being consultants for and/or receiving research funding from various pharmaceutical companies. The study was partly supported by grants from the Leukemia and Lymphoma Society of America and Fulbright Franco-American Commission/Foundation.