A phase 2 study of intravenous panobinostat in patients with castration-resistant prostate cancer Journal Article
| Authors: | Rathkopf, D. E.; Picus, J.; Hussain, A.; Ellard, S.; Chi, K. N.; Nydam, T.; Allen-Freda, E.; Mishra, K. K.; Porro, M. G.; Scher, H. I.; Wilding, G. |
| Article Title: | 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/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. © 2013 Springer-Verlag Berlin Heidelberg. |
| Keywords: | adult; cancer survival; clinical article; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; constipation; drug tolerability; fatigue; diarrhea; drug efficacy; drug safety; hypophosphatemia; side effect; solid tumor; treatment duration; antineoplastic agents; prostate specific antigen; progression free survival; multiple cycle treatment; phase 2 clinical trial; anemia; leukopenia; nausea; thrombocytopenia; vomiting; dehydration; qt prolongation; carcinoembryonic antigen; weight reduction; creatinine blood level; arthralgia; backache; dyspnea; fever; prostate cancer; prostate-specific antigen; prostatic neoplasms; hypokalemia; hyponatremia; hypotension; multicenter study; drug response; muscle weakness; peripheral edema; thrombocyte count; histone deacetylase inhibitors; hydroxamic acids; limb pain; clinical effectiveness; orchiectomy; indoles; st segment; infusions, intravenous; panobinostat; drug exposure; dysgeusia; hypocalcemia; castration resistant prostate cancer; decreased appetite; electrocardiography monitoring; deacetylase inhibitor |
| Journal Title: | Cancer Chemotherapy and Pharmacology |
| Volume: | 72 |
| Issue: | 3 |
| ISSN: | 0344-5704 |
| Publisher: | Springer |
| Date Published: | 2013-09-01 |
| Start Page: | 537 |
| End Page: | 544 |
| Language: | English |
| DOI: | 10.1007/s00280-013-2224-8 |
| PROVIDER: | scopus |
| PUBMED: | 23820963 |
| PMCID: | PMC3970811 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 October 2013" - "CODEN: CCPHD" - "Source: Scopus" |
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