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Updated: May 10, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A phase 2 study of intravenous panobinostat in patients with castration-resistant prostate cancer
Dana E Rathkopf1, Joel Picus, Arif Hussain
1Memorial Sloan-Kettering Cancer Center, New York, NY, USA. rathkopd@mskcc.org
Purpose:
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.
Methods:
IV panobinostat (20 mg/m(2)) was administered to patients on days 1 and 8 of a 21-day cycle. Tumor response was assessed by imaging every 12 weeks (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 ≥4 weeks. Safety monitoring was routinely performed and included electrocardiogram monitoring.
Results:
Of 35 enrolled patients, four (11.4 %) were alive without progression of disease at 24 weeks. 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 %).
Conclusions:
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.
Insights
Panobinostat did not demonstrate significant clinical activity in patients with castration-resistant prostate cancer (CRPC). Further investigation as a single agent is not recommended due to insufficient efficacy in this patient population.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Panobinostat is a pan-deacetylase inhibitor with preclinical activity against malignant cells.
- Castration-resistant prostate cancer (CRPC) is an advanced stage of prostate cancer with limited treatment options.
Purpose of the Study:
- To evaluate the efficacy and safety of intravenous (IV) panobinostat in patients with previously treated CRPC.
- To determine the 24-week progression-free survival rate as the primary endpoint.
Main Methods:
- A phase 2 study administered IV panobinostat (20 mg/m(2)) on days 1 and 8 of a 21-day cycle.
- Tumor response was assessed by imaging, and PSA response was defined as a 50% decrease from baseline.
- Safety monitoring included electrocardiogram monitoring.
Main Results:
- Only 11.4% of patients (4 out of 35) were alive without disease progression at 24 weeks.
- No patient achieved a 50% or greater prostate-specific antigen (PSA) decline.
- Common toxicities included fatigue, thrombocytopenia, nausea, and decreased appetite.
Conclusions:
- Intravenous panobinostat did not show sufficient clinical activity as a single agent in CRPC patients.
- Despite a strong scientific rationale, further investigation of panobinostat alone in this setting is not warranted.
