Phase I Study of Entinostat in Combination with Enzalutamide for Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer

[摘要] Background. Entinostat inhibits prostate cancer (PCa) growthand suppresses Treg cell function in vitro and in vivo.Methods. This was a phase I study to explore the safety andpreliminary efficacy of entinostat (3 and 5 mg orally per week)in combination with enzalutamide in castration resistant PCa(CRPC). The study was carried out in an open-label two-cohortdesign. Patients who had developed disease progression on orwere eligible for enzalutamide were enrolled in the study. Thesafety profile of the combination therapy, Prostate specificantigen (PSA) levels, the pharmacokinetics of enzalutamideafter entinostat administration, peripheral T-cell subtype(including Treg quantitation), and mononuclear cell (PBMC)histone H3 acetylation were analyzed.Results. Six patients with metastatic CRPC were enrolled.There was no noticeable increment of fatigue related toentinostat. Toxicities possibly or probably related to entinostator the combination therapy included grade 3 anemia 1/6(17%), grade 2 white blood cell (WBC) decrease 1/6 (17%),and other self-limiting grade 1 adverse events (AEs). Medianduration of treatment with entinostat was 18 weeks.Entinostat did not affect the steady plasma concentration ofenzalutamide. Increased PBMC histone H3 acetylation wasobserved in blood samples. No evident T-cell subtype changeswere detected, including in Treg quantitation.Conclusion. Entinostat 5 mg weekly in combination withenzalutamide showed an acceptable safety profile in thissmall phase I study. A planned phase II part of the trial wasterminated because of sponsor withdrawal. The Oncologist2021;26:e2136–e2142.

[学科分类] 地质学

[关键词] Entinostat;Enzalutamide;Combination;Prostate cancer