A phase 2 study of intravenous panobinostat in patients with castration-resistant prostate cancer

Abstract

Panobinostat, a pan-deacetylase inhibitor, increases acetylation of proteins associated with growth and survival of malignant cells. This phase 2 study evaluated the efficacy of intravenous (IV) panobinostat in patients with castration-resistant prostate cancer (CRPC) who had previously received chemotherapy. The primary end point was 24-week progression-free survival. Secondary end points included safety, tolerability, and the proportion of patients with a prostate-specific antigen (PSA) decline. IV panobinostat (20mg/m(2)) was administered to patients on days 1 and 8 of a 21-day cycle. Tumor response was assessed by imaging every 12weeks (4 cycles) according to modified response evaluation criteria in solid tumors (Scher et al. in Clin Cancer Res 11:5223-5232, 23), and PSA response was defined as a 50% decrease from baseline maintained for ≥4weeks. Safety monitoring was routinely performed and included electrocardiogram monitoring. Of 35 enrolled patients, four (11.4%) were alive without progression of disease at 24weeks. PSA was evaluated in 34 (97.1%) patients: five (14.3%) patients demonstrated a decrease in PSA but none ≥50%; one patient (2.9%) had carcinoembryonic antigen as a marker of his prostate cancer, which declined by 43%. Toxicities regardless of relationship to panobinostat included fatigue (62.9%), thrombocytopenia (45.7%), nausea (51.4%), and decreased appetite (37.1%). Despite promising preclinical data and scientific rationale, treatment with IV panobinostat did not show a sufficient level of clinical activity to pursue further investigation as a single agent in CRPC.