Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure

BJU Int. 2013 Jan;111(1):44-52. doi: 10.1111/j.1464-410X.2012.11404.x. Epub 2012 Aug 29.

Abstract

Objective: To determine the efficacy and toxicity of danusertib (formerly PHA-739358) administered i.v. over two different dosing schedules with equivalent dose intensity in patients with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment.

Patients and methods: In this open-label, multicentre phase II trial 88 patients were randomly assigned (1:1 ratio) to receive either danusertib 330 mg/m(2) over 6 h i.v. on days 1, 8 and 15 (arm A, n = 43) or 500 mg/m(2) over 24 h i.v. on days 1 and 15 (arm B, n = 38), every 4 weeks. The primary endpoint chosen for this exploratory study was PSA response rate at 3 months.

Results: Sixty patients (31/43 in arm A and 29/38 in arm B) were evaluable for the primary endpoint. Median progression-free survival was 12 weeks in both arms. PSA response occurred in one patient in each arm; best overall response was stable disease in eight (18.6%) and 13 (34.2%) patients in arms A and B, respectively. Eleven out of 81 (13.6%) treated patients had stable disease for ≥6 months. Danusertib was generally well tolerated; the most common grade 3 and 4 drug-related adverse event was neutropenia which occurred in 37.2% (arm A) and 15.8% (arm B) of the patients.

Conclusion: Danusertib monotherapy shows minimal efficacy in patients with castration-resistant prostate cancer. Further studies are required to establish specific biomarkers predictive for either response or prolonged disease stabilization.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Aurora Kinases
  • Benzamides / administration & dosage*
  • Benzamides / adverse effects
  • Bone Neoplasms / secondary
  • Castration
  • Disease-Free Survival
  • Docetaxel
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Humans
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Prostatic Neoplasms / drug therapy*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Taxoids / therapeutic use*
  • Treatment Failure

Substances

  • Antineoplastic Agents
  • Benzamides
  • Pyrazoles
  • Taxoids
  • Docetaxel
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • danusertib