Journal Article

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

Nydam, Thomas, Allen-Freda, Erin, Chi, Kim Nguyen, Scher, Howard I., Porro, Maria Grazia, Wilding, George, Picus, Joel, Mishra, Kaushal Kishor, Rathkopf, Dana E., Hussain, Arif, Ellard, Susan

2013

Overview

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.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Aged / Aged, 80 and over / Antineoplastic agents / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - adverse effects / Antineoplastic Agents - therapeutic use / Biological and medical sciences / Cancer Research / Disease-Free Survival / Gynecology. Andrology. Obstetrics / Histone Deacetylase Inhibitors - administration & dosage / Histone Deacetylase Inhibitors - adverse effects / Histone Deacetylase Inhibitors - therapeutic use / Humans / Hydroxamic Acids - administration & dosage / Hydroxamic Acids - adverse effects / Hydroxamic Acids - therapeutic use / Indoles - administration & dosage / Indoles - adverse effects / Indoles - therapeutic use / Infusions, Intravenous / Male / Male genital diseases / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / Nephrology. Urinary tract diseases / Oncology / Orchiectomy / Original Article / Panobinostat / Pharmacology. Drug treatments / Pharmacology/Toxicology / Prostate-Specific Antigen - blood / Prostatic Neoplasms - drug therapy / Prostatic Neoplasms - pathology / Prostatic Neoplasms - surgery / Treatment Outcome / Tumors / Tumors of the urinary system / Urinary tract. Prostate gland