Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance?

Ann Oncol. 2012 Nov;23(11):2943-2947. doi: 10.1093/annonc/mds119. Epub 2012 Jul 5.

Abstract

Background: Abiraterone and docetaxel are both approved treatments for men with metastatic castration-resistant prostate cancer (mCRPC). Abiraterone pre-docetaxel is currently undergoing evaluation in a phase III study. In vitro studies indicate that taxanes may act by disrupting androgen receptor signalling. We hypothesised that prior abiraterone exposure would adversely impact docetaxel efficacy.

Patients and methods: We retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone, using Prostate Cancer Working Group and radiological criteria.

Results: Of the 54 patients treated with abiraterone, 35 subsequently received docetaxel. Docetaxel resulted in a prostate-specific antigen (PSA) decline of ≥50% in nine patients [26%, 95% confidence interval (CI) 13% to 43%], with a median time to PSA progression of 4.6 months (95% CI 4.2% to 5.9%). PSA declines ≥30% were achieved by 13 patients (37%, 95% CI 22% to 55%). The median overall survival was 12.5 months (95% CI 10.6-19.4). All patients who failed to achieve a PSA fall on abiraterone and were deemed abiraterone-refractory were also docetaxel-refractory (N = 8). In the 24 patients with radiologically evaluable disease, partial responses were reported in four patients (11%), none of whom were abiraterone-refractory.

Conclusion: The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Receptor Antagonists / therapeutic use
  • Androstenes
  • Androstenols / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Disease Progression
  • Docetaxel
  • Drug Interactions
  • Drug Resistance, Neoplasm
  • Humans
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality*
  • Receptors, Androgen / metabolism
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors
  • Taxoids / therapeutic use*
  • Testosterone / blood

Substances

  • Androgen Receptor Antagonists
  • Androstenes
  • Androstenols
  • Antineoplastic Agents
  • Receptors, Androgen
  • Taxoids
  • Docetaxel
  • Testosterone
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • Prostate-Specific Antigen
  • abiraterone