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

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

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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/m2) 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.

Original languageEnglish
Pages (from-to)537-544
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume72
Issue number3
DOIs
StatePublished - Sep 2013

Keywords

  • Deacetylase inhibitor
  • Panobinostat
  • Prostate cancer
  • Prostate-specific antigen

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