Cancer Chemotherapy and Pharmacology

, Volume 72, Issue 3, pp 537–544 | Cite as

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

  • Dana E. RathkopfEmail author
  • 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
Original Article



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.


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.


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 %).


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.


Prostate cancer Deacetylase inhibitor Panobinostat Prostate-specific antigen 



This study was funded by Novartis Pharmaceuticals Corporation. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank Kerry K. Brinkman, PhD, for medical editorial assistance with this manuscript.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Dana E. Rathkopf
    • 1
    Email author
  • Joel Picus
    • 2
  • Arif Hussain
    • 3
  • Susan Ellard
    • 4
  • Kim Nguyen Chi
    • 5
  • Thomas Nydam
    • 6
  • Erin Allen-Freda
    • 6
  • Kaushal Kishor Mishra
    • 6
  • Maria Grazia Porro
    • 7
  • Howard I. Scher
    • 1
  • George Wilding
    • 8
  1. 1.Memorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Siteman Cancer Center, Barnes-Jewish HospitalWashington University School of MedicineSt. LouisUSA
  3. 3.Greenebaum Cancer CenterUniversity of MarylandBaltimoreUSA
  4. 4.British Columbia Cancer AgencyKelownaCanada
  5. 5.British Columbia Cancer AgencyVancouverCanada
  6. 6.Novartis Pharmaceuticals CorporationEast HanoverUSA
  7. 7.Novartis Pharma AGBaselSwitzerland
  8. 8.Paul P. Carbone Cancer CenterUniversity of WisconsinMadisonUSA

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