A randomised phase 2 study combining LY2181308 sodium (survivin antisense oligonucleotide) with first-line docetaxel/prednisone in patients with castration-resistant prostate cancer.

Abstract

Castration-resistant prostate cancer (CRPC) is partially characterised by overexpression of antiapoptotic proteins, such as survivin. In this phase 2 study, patients with metastatic CRPC (n=154) were randomly assigned (1:2 ratio) to receive standard first-line docetaxel/prednisone (control arm) or the combination of LY2181308 with docetaxel/prednisone (experimental arm). The primary objective was to estimate progression-free survival (PFS) for LY2181308 plus docetaxel. Secondary efficacy measures included overall survival (OS), several predefined prostate-specific antigen (PSA)-derived end points, and Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores. The median PFS of treated patients for the experimental arm (n=98) was 8.64 mo (90% confidence interval [CI], 7.39-10.45) versus 9.00 mo (90% CI, 7.00-10.09) in the control arm (n=51; p=0.755). The median OS for the experimental arm was 27.04 mo (90% CI, 19.94-33.41) compared with 29.04 mo (90% CI, 20.11-39.26; p=0.838). The PSA responses (≥ 50% PSA reduction), BPI, and FACT-P scores were similar in both arms. In the experimental arm, patients had a numerically higher incidence of grades 3-4 neutropenia, anaemia, thrombocytopenia, and sensory neuropathy. In conclusion, this study failed to detect a difference in efficacy between the two treatment groups.

• Authors: Paweł Wiechno, Bradley G Somer, Begoña Mellado, Piotr L Chłosta, José Manuel Cervera Grau, Daniel Castellano, Christoph Reuter, Michael Stöckle, Jörn Kamradt, Joanna Pikiel, Ignacio Durán, Steffen Wedel, Sophie Callies, Valérie André, Karla Hurt, Jacqueline Brown, Michael Lahn, Bernhard Heinrich
• Journal: European urology (Eur Urol) Vol. 65 Issue 3 Pg. 516-20 (Mar 2014) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 24246407 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• LY 2181308
• Oligonucleotides
• Taxoids
• Docetaxel
• Prednisone

Topics

• Antineoplastic Agents (administration & dosage)
• Disease-Free Survival
• Docetaxel
• Drug Therapy, Combination
• Humans
• Male
• Oligonucleotides (administration & dosage)
• Prednisone (administration & dosage)
• Prostatic Neoplasms, Castration-Resistant (drug therapy)
• Taxoids (administration & dosage)