Abiraterone before Taxotere/Docetaxel chemotherapy may cause resistance to Taxotere/Docetaxel

[JimJimJimJim]

Jim Marshall (not a doctor) said ...

Abiraterone (not currently covered by the PBS in Australia (Jul 2012)) is approved for use after Taxotere/Docetaxel chemotherapy by the FDA (USA) and TGA (Australia).

We reported that here:

http://advancedprost...rostate-cancer/

More recently, the use of Abiraterone before Taxotere/Docetaxel chemotherapy has shown some success.

We reported that here:

http://advancedprost...omild-symptoms/

But there may be a small fly in the ointment for this use of Abiraterone before Taxotere/Docetaxel chemotherapy.

The article below says in the small number of cases they examined, it seems that use of Abiraterone before Taxotere/Docetaxel chemotherapy may make the Taxotere/Docetaxel chemotherapy less effective.

More, if a man did not respond to Abiraterone, he also did not respond to the Taxotere/Docetaxel chemotherapy. This seems to be further evidence to support the theory that Abiraterone and Taxotere/Docetaxel chemotherapy work in the same way (affecting androgen receptor (AR) signalling.)

... end Jim

Ann Oncol. 2012 Jul 5. [Epub ahead of print]

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

Mezynski J, Pezaro C, Bianchini D, Zivi A, Sandhu S, Thompson E, Hunt J, Sheridan E, Baikady B, Sarvadikar A, Maier G, Reid AH, Mulick Cassidy A, Olmos D, Attard G, de Bono J.

Source

Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.

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.

PMID: 22771826

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.