title: Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance?
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.
  
  
  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.
  
  
  CONCLUSIONS
  The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients.
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: J
authors: J
authors: Mezynski
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: C
authors: C
authors: Pezaro
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: D
authors: D
authors: Bianchini
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: A
authors: A
authors: Zivi
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: S
authors: S
authors: Sandhu
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: E
authors: E
authors: Thompson
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: J
authors: J
authors: Hunt
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: E
authors: E
authors: Sheridan
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: B
authors: B
authors: Baikady
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: A
authors: A
authors: Sarvadikar
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: G
authors: G
authors: Maier
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: A H M
authors: AHM
authors: Reid
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: A
authors: A
authors: Mulick Cassidy
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: D
authors: D
authors: Olmos
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK. Electronic address: Gerhardt.attard@icr.ac.uk.
authors: G
authors: G
authors: Attard
authors: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors: J
authors: J
authors: de Bono
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D059002:Androgen Receptor Antagonists / Q000627:therapeutic use; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D000077143:Docetaxel; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D011944:Receptors, Androgen / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000627:therapeutic use*; D013739:Testosterone / Q000097:blood
chemical_list: D059002:Androgen Receptor Antagonists; D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel; D013739:Testosterone; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D017430:Prostate-Specific Antigen; C089740:abiraterone