A new prostate cancer drug could extend the lives of patients with an aggressive form of the disease, the first phase of a clinical trial suggests.
British scientists found that the drug abiraterone significantly shrunk tumours and blocked prostate specific antigen (PSA), a protein that feeds prostate cancer development, in almost 80 per cent of study subjects.
"These men have very aggressive prostate cancer which is exceptionally difficult to treat and almost always proves to be fatal," lead researcher, Dr. Johann de Bono of The Institute of Cancer Research, said in a statement.
"We hope that abiraterone will eventually offer them real hope of an effective way of managing their condition and prolonging their lives."
The findings are published in the Journal of Clinical Oncology.
Abiraterone is currently only available through clinical trials. However, the researchers hope that it will hit the market by 2011.
The researchers studied 21 men with prostate cancer that is so aggressive, it is believed that the tumour tissue can actually produce its own supply of the hormones that encourage tumour growth.
This form of prostate cancer is resistant to current drug treatment, which only blocks the production of hormones created by the testicles.
Abiraterone can block hormones produced anywhere in the body.
The patients were followed for up to two-and-a-half years, and experienced few side effects during the time they took the drug.
Some patients were able to discontinue their use of morphine for pain related to their disease.
While this study is small, this is only the first of three research phases. Another clinical trial of about 1,200 patients is already underway.
According to the Canadian Cancer Society, prostate cancer is the most common form of cancer in Canadian men, with one in seven men projected to develop the disease in his lifetime.
Abstract:
Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly Remains Hormone Driven
Gerhardt Attard, Alison H.M. Reid, Timothy A. Yap, Florence Raynaud, Mitch Dowsett, Sarah Settatree, Mary Barrett, Christopher Parker, Vanessa Martins, Elizabeth Folkerd, Jeremy Clark, Colin S. Cooper, Stan B. Kaye, David Dearnaley, Gloria Lee, and Johann S. de Bono
Purpose: Studies indicate that castration-resistant prostate cancer (CRPC) remains driven by ligand-dependent androgen receptor (AR) signaling. To evaluate this, a trial of abiraterone acetate--a potent, selective, small-molecule inhibitor of cytochrome P (CYP) 17, a key enzyme in androgen synthesis--was pursued.
Patients and Methods: Chemotherapy-na锟絭e men (n = 21) who had prostate cancer that was resistant to multiple hormonal therapies were treated in this phase I study of once-daily, continuous abiraterone acetate, which escalated through five doses (250 to 2,000 mg) in three-patient cohorts.
Results: Abiraterone acetate was well tolerated. The anticipated toxicities attributable to a syndrome of secondary mineralocorticoid excess--namely hypertension, hypokalemia, and lower-limb edema--were successfully managed with a mineralocorticoid receptor antagonist. Antitumor activity was observed at all doses; however, because of a plateau in pharmacodynamic effect, 1,000 mg was selected for cohort expansion (n = 9). Abiraterone acetate administration was associated with increased levels of adrenocorticotropic hormone and steroids upstream of CYP17 and with suppression of serum testosterone, downstream androgenic steroids, and estradiol in all patients. Declines in prostate-specific antigen (PSA) 30%, 50%, and 90% were observed in 14 (66%), 12 (57%), and 6 (29%) patients, respectively, and lasted between 69 to 578 days. Radiologic regression, normalization of lactate dehydrogenase, and improved symptoms with a reduction in analgesic use were documented.
Conclusion: CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC. These data confirm that CRPC commonly remains dependent on ligand-activated AR signaling.
