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

Abstract

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.

• Authors: Dana E Rathkopf, Joel Picus, Arif Hussain, Susan Ellard, Kim Nguyen Chi, Thomas Nydam, Erin Allen-Freda, Kaushal Kishor Mishra, Maria Grazia Porro, Howard I Scher, George Wilding
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 72 Issue 3 Pg. 537-44 (Sep 2013) ISSN: 1432-0843 [Electronic] Germany
• PMID: 23820963 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Indoles
• Panobinostat
• Prostate-Specific Antigen

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Disease-Free Survival
• Histone Deacetylase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Humans
• Hydroxamic Acids (administration & dosage, adverse effects, therapeutic use)
• Indoles (administration & dosage, adverse effects, therapeutic use)
• Infusions, Intravenous
• Male
• Middle Aged
• Orchiectomy
• Panobinostat
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (drug therapy, pathology, surgery)
• Treatment Outcome