Abiraterone acetate for hormone-resistant prostate cancer

A paper published today in the Journal of Clinical Oncology suggests that a new agent has been identified for the treatment of end-stage prostate cancer. The paper is being quoted in the media and is likely to reinvigorate discussion about the merits and risks of agents targeting hormone synthetic pathways.

The paper comes from a group headquartered in London’s Royal Marsden Hospital. It describes a Phase I study of abiraterone acetate, which blocks an enzyme known as cytochrome P17, needed for the production of testosterone. The main purpose of Phase I trials is to test toxicity, not to establish effectiveness. Readers should be aware that data from Phase II studies have already been reported — but not formally published (see one our reports from ASCO earlier this year), and that a Phase III trial is already recruiting patients.

The Phase I study focused on 21 men who had failed traditional hormone manipulations but who had received no chemotherapy. Three-patient groups received once daily abiraterone in doses up to 2 mg. Overall, the abiraterone was reasonably well tolerated. Its administration was associated with reductions in serum levels of prostate-specific antigen (PSA), a protein produced by prostate cancer cells. It was also associated with reduction of radiological evidence of prostate cancer and with improvement in symptoms as partly evidenced in reduced use of pain medication. No data were presented relating to survival.

The emphasis on complete hormonal blockade is not a new concept. Indeed, with the production of flutamide (Eulexin; Schering Plough) and competing oral anti-androgens (nilutamide, bicalutamide) years of research went into proving the merits of what became known as the [Fernand] Labrie Hypothesis: blocking adrenal androgens is a clinically important part of androgen deprivation. The new agent, abiraterone, seeks to work at a level different from the oral anti-androgens, which blocked the action of androgen receptor (AR) in the nucleus. Abiraterone works by interfering with production of testosterone and its derivatives altogether.

10 Responses

  1. My father has advanced prostate cancer and was recently diagnosed with bones mets. His was on ketoconazole but had serious side effects and stopped. At that time he became very ill and was found to have mets in the spine T11, L2 and L3. His PSA was up to 88 but has gone down to 18.4. He is still receiving quarterly Lupon injections but they have removed Casodex. His has decided at this time to not be treated further with any further meds. He is on pain meds. Would this be beneficial for my father?

    Thank you.

  2. Dear Ms Peck: Your father’s PSA has likely gone down because of an effect called antiandrogen withdrawal. When patients stop using drugs like bicalutamide (Casodex), their PSA can dxrop for a while before starting to go back up again.

    While it is possible that abiraterone could help your father, unfortunately he would not seem to be eligible for the current clinical trials. Only patients who have already tried and failed docetaxel (Taxotere) therapy are eligible for the Phase III trial of abiraterone.

    You might find it helpful to join the Social Network (see the button in the upper left) where you could talk to other men and women who have experience of what you and your father are going through.

  3. I meet the criteria for being selected for Phase III trial of abiraterone.
    Any idea who we contact?

  4. Dear Mr Christensen: Click on the link in the original post above that says, “a phase III trial is already recruiting patients.” In that link, look for the words in bold blue type that say, “Show 37 study locations.” Click that link and you will be able to see the full list of trial sites, with contact information (phone numbers included).

  5. 3 Years ago at 55 years of age I was diagnosed with a Stage 2-3 Prostate Cancer. I received 45 treatments of IMRT and was put on Lupron. Within the last 8 months my PSA started to rise to a 12.5 as of last week. What are the symtoms of Metassis in the Pelvis Bones or Spine area? Would there be pain?

  6. Dear Mr. Hatten: We have forwarded your question to Ask Arthur. Just go to the bottom of the Ask Arthur page, and you will find your question. Arthur should answer it pretty soon. Thanks for your interest.

  7. I would like to apply for testing in phase III of abiraterone acetate. Chemotherapy (docetaxel) brought my PSA down to 30, but over the past 6 months it has climbed to 111 despite continued chemo. I can also be reached by phone a 425-269-8683

  8. Dear Mr Keyes: The “New” Prostate Cancer InfoLink cannot assist you directly with enrollment in the abiraterone clinical trials.

    Please go to the trial description on ClinicalTrials.gov, scroll down, click on the words “Show 45 Study Locations,” and then you will be able to find the clinical trial site nearest to you, complete with a name and a phone number to call.

  9. Hi, I am a candidate for the phase 3 trial in the UK and to keep everyone informed I have started a blog.

    My blog and details of the trial are on http://theboyceys.com


  10. Excellent post thank you for the info

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