Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100)

Ann Oncol. 2013 Jul;24(7):1807-1812. doi: 10.1093/annonc/mdt136. Epub 2013 Apr 10.

Abstract

Background: Androgen receptor (AR) signalling remains critically important in metastatic castration-resistant prostate cancer (mCRPC) as confirmed by recent phase III trials, showing a survival advantage for abiraterone acetate and enzalutamide (MDV3100). The antitumour activity of abiraterone and prednisolone in patients pre-treated with enzalutamide is as yet unknown.

Patients and methods: We investigated the antitumour activity of abiraterone and prednisolone in patients with mCRPC who had progressed following treatment with docetaxel (Taxotere) and enzalutamide. Clinical data were retrospectively analysed for prostate-specific antigen (PSA) and RECIST responses, clinical benefit and survival.

Results: Thirty-eight patients were included in the analysis. The median age was 71 years (range 52-84); metastatic sites included bone disease in 37 patients (97%), lymph nodes in 15 patients (39%) and visceral disease in 10 patients (26%). Abiraterone was well tolerated. Three patients (8%) attained a PSA response, defined as ≥50% decline in PSA confirmed after ≥4 weeks, while seven patients (18%) had a ≥30% PSA decline. The median progression-free survival (PFS) was 2.7 months (95% CI 2.3-4.1). Of the 12 patients assessable radiologically, only 1 (8%) attained a confirmed partial response.

Conclusion: Abiraterone and prednisolone have modest antitumour activities in patients with mCRPC pretreated with docetaxel and enzalutamide.

Keywords: CRPC; enzalutamide; abiraterone; hormonal manipulations.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenes
  • Androstenols / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Bone Neoplasms / blood
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Clinical Trials, Phase III as Topic
  • Disease-Free Survival
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Humans
  • Kallikreins / blood
  • Male
  • Middle Aged
  • Nitriles
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / pharmacology
  • Prednisolone / administration & dosage
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Taxoids / pharmacology*
  • Treatment Outcome

Substances

  • Androstenes
  • Androstenols
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • enzalutamide
  • Prednisolone
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • abiraterone