A Phase III Trial Involving Enzalutamide in Men with Metastatic, Hormone-Resistant Prostate Cancer.

The Alliance for Clinical Trials in Oncology is conducting a Phase III clinical trial of enzalutamide (Xtandi®) with or without abiraterone acetate (Zytiga®) and prednisone in men with hormone-refractory, metastatic prostate cancer with the hope of improving overall survival.  Details of this trial can be found at the U.S. National Institutes of Health (NIH) clinical trials website, ClinicalTrials.gov.  Enzalutamide works by disrupting a tumor cells’ ability to use testosterone by blocking the cell’s testosterone receptors and prevents the production of androgens within the cell itself.  Zytiga® inhibits two distinct steps in the production of testosterone from cholesterol even in tumor cells by blocking a cell membrane enzyme called CYP17A1.  Both drugs have been approved by the Food and Drug Administration for treatment of men with metastatic, hormone-refractory prostate cancer.  For further information on these two agents, see the January 3rd, 2012 website blog.

Affinity: A Phase III Trial Using Custirsen and Jevtana® for Men with Metastatic Hormone-Resistant Prostate Cancer.

The goal of the Phase III Affinity Trial is to test whether adding an experimental drug called custirsen to Jevtana® (cabazitaxel) chemotherapy can help treat men with hormone-resistant prostate cancer. In the latter case, chemotherapy with taxotere (docetaxel®) or  Jevtana® (cabazitaxel) are often the first lines of chemotherapy adminstered. However, they are often accompanied by undesirable side effects and patients may eventually become resistant to the treatments. The current trial will examine whether adding the drug custirsen to the treatment with Jevtana® can help slow the progression of the prostate cancer. Custirsen is an experimental drug designed to block the production of a protein (clusterin) associated with treatment resistance in many cancers. Phase 2 trials suggest that custirsen may improve overall survival for patients with prostate cancer. While Jevtana® has been approved by the Food and Drug Administration, custirsen has not yet been approved. For additional details, see the  following link to the Affinity trial as well as the January 3rd, 2012 website blog describing various prostate therapies in differing stages of clinical development.

Metformin Aids in the Stabilization of Metastatic Prostate Cancer

An article published in the January 4th, 2014 issue of the journal European Urology reported the outcome of a Swiss trial involving men with hormone-resistant (refractory) prostate cancer (defined as a testosterone level of less than 50 ng/dL with progressive disease) who were given the anti-diabetic drug metformin. For the trial, 44 non-diabetic men who had not been treated with chemotherapy for progressive, metastatic hormone-resistant prostate cancer causing few or no symptoms were given 1,000 mg (one gram) of metformin twice a day until disease progression. Assessment of disease status- included computer tomography of the abdomen, pelvis and chest, bone scanning and serum prostate cancer-specific antigen (PSA) level measurement- was conducted every 12 weeks. After initiation of metformin therapy, 36% of the group was progression-free at 12 weeks and 9% were still progression-free at 24 weeks. PSA doubling time, a measure of disease progression, was beneficially prolonged in 52% of patients after the initiation of metformin. It should be noted that metformin is also associated with improved insulin sensitivity. It should be administered only under a physician’s approval, care and control.

PROSPECT: A Phase III Clinical Trial of the Immunotherapy Vaccine Prostvac in Asymptomatic Hormone-Resistant Prostate Cancer Patients.

The goal of the Prospect Trial is to enhance a man’s immune system to fight prostate cancer. It is a Phase III trial for metastatic, hormone-resistant prostate cancer patients who are either asymptomatic or minimally symptomatic. The trial utilizes the investigational immunotherapy, Prostvac, a therapeutic pox virus cancer vaccine directed at PSA-producing cells. It is administered with or without GM-CSF (granulocyte macrophage colony-stimulating factor). GM-CSF is a protein secreted by immune system cells that functions as a white blood cell growth factor. Prostvac is delivered via a series of injections over five months. The end point of the trial is to improve overall survival.  Prostvac was developed at the National Cancer Institute (NCI), the largest of the institutes of the National Institutes of Health (NIH), Bethesda, Maryland. There is considerable interest in administering this vaccine to men in earlier stages of their disease. For more information such as concerning qualification and locations of the trial, see the following link. One can also find information at the National Cancer Institute’s clinical trial website, http://www.cancer.gov/clinicaltrials or call the NCI’s help line at 1-800-4-CANCER. Prostvac was also discussed in earlier blogs posted on this website on Sept. 20th, 2011, January 3rd, 2012, and the Bavarian Nordic website, who are co-developers of Prostvac. For a fact sheet on Prostvac and its results in previous trials, see the following link.