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

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

J Mezynski  1 , C Pezaro  1 , D Bianchini  1 , A Zivi  1 , S Sandhu  1 , E Thompson  1 , J Hunt  1 , E Sheridan  1 , B Baikady  1 , A Sarvadikar  1 , G Maier  1 , A H M Reid  1 , A Mulick Cassidy  1 , D Olmos  1 , G Attard  2 , J de Bono  1
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Free article
Clinical Trial

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

J Mezynski et al. Ann Oncol. 2012 Nov.
Free article

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.

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