Romidepsin (FK228), a histone deacetylase inhibitor: Final results of a phase II study in metastatic hormone refractory prostate cancer (HRPC)

15507 Background: Romidepsin is a bicyclic depsipeptide that inhibits histone deacetylase (HDAC). Translocations fusing TMPRSS2 gene and ERG oncogenic factor is associated with elevated HDAC-1 expression. HDAC inhibition results in accumulation of hyperacetylated histone proteins resulting in G1 and G2/M arrest, differentiation of transformed cells and apoptosis. Romidepsin can also inhibit HSP90, ablating androgen receptor expression. This is the 1st study to report activity of an HDAC inhibitor in HRPC. Methods: Romidepsin was administered intravenously at 13mg/m2 on days 1, 8 and 15 of a 28-day schedule. A 2-stage design was used. Eligibility criteria included: no prior chemotherapy, metastatic disease, QTcB <470msec, Karnofsky PS =80. The primary endpoint was to determine rate of disease control (complete response [CR], partial response [PR], stable disease [SD] for 6 months). Secondary endpoints were PSA response rate (RR), time to PSA and objective disease progression, safety profile, effect on dise...