First line treatment for patients with metastatic prostate cancer generally consists of androgen deprivation therapy. This can be achieved by administering gonadotropin releasing hormone analogs, or even by surgical castration. Even though the majority of patients initially respond to this treatment, for most patients the tumor eventually progresses despite castration levels of testosterone and reaches a stage known as “castration resistant” disease. The median duration of disease control is only 13 to 22 months, and overall survival is 28 to 36 months.
Standard treatment for patients with castration resistant prostate cancer includes chemotherapy with docetaxel. Docetaxel improves overall survival by two to three months, so there is a need to develop less toxic treatments, to delay further progression of the disease, and prolong overall survival. It is thought that these patients might still benefit from second and third line hormonal therapies. Historically, physicians have also added an anti-androgen to medical castration, including bicalutamide, to try to restore sensitivity to hormonal manipulation.
Dr. Cora Sternberg of the San Camillo Forlanini Hospitals, Rome, and Coordinator of this study says, “Novel hormonal therapies with a different mechanism of action than bicalutamide have the potential to improve survival and quality of life in patients for whom initial hormonal therapy has failed”.
EORTC trial 1211, a phase II randomized comparative trial of TAK-700 (orteronel) versus bicalutamide, has just opened for patients with metastatic prostate cancer after failure of first line treatment with luteinizing hormone-releasing hormone agonists or surgical castration. TAK-700 is a selective inhibitor of a key enzyme involved in the production pathway of steroid hormones in both the gonads and the adrenal glands, and it is expected to suppress sex hormone levels (testosterone) in circulation and in hormone-sensitive cancers such as prostate cancer. Until now it has primarily been evaluated in patients who have failed hormonal manipulations.
EORTC trial 1211 plans to accrue 200 patients and will be conducted in 30 sites in 6 countries:
Belgium, Italy, Poland, Spain, the Netherlands, and the United Kingdom. This trial is coordinated by the EORTC Genito-Urinary Cancers Group in collaboration with the EORTC Imaging Group and is supported by an educational grant from Millennium Pharmaceuticals.
For more information concerning EORTC trial 1211 please contact: www.eortc.org/contact
John Bean, PhD
EORTC, Medical Science Writer