The latest edition of the Johns Hopkins Health Alerts (July 9th) cites two blood tests that can provide important information which, when coupled with a physician’s clinical judgment, can more accurately predict the need for a biopsy to confirm or deny the presence of prostate cancer. The Prostate Health Index (phi test) measures blood levels of PSA, free PSA and an early precursor of PSA called proPSA or p2PSA. The 4Kscore measures total, free and intact PSA and in addition, measures an enzyme called human kallikrein2 (hK2) which is elevated in men with prostate cancer. The significance of these test results in discussed in the linked article. One must keep in mind that these tests are new and do not have a long track record of results. They can also be marketed without proof of benefit. For more information, see the April 24th, 2014 blog post on this website.
Takeda Oncology Company and Millenium announced recently that they are halting the development of TAK-700 (Ortoronel) due to poor Phase III trial results in men with metastatic prostate cancer who have not had previous chemotherapy. The drug failed to extend survival time. TAK-700 has been previously discussed in blogs published on this website on June 3rd and November 21st, 2011. TAK-700 is an oral, non-steroidal, androgen (e.g. testosterone) synthesis inhibitor. End points of the clinical studies also included delay in disease progression in addition to extending survival time.
It was recently announced that the Finnish drugmaker Orion Corporation and Bayer Pharmaceuticals have entered an agreement to jointly develop Orion’s ODM-201, an oral, androgen receptor inhibitor. Bayer and Orion plan to jointly start the clinical Phase III program in 2014 to further evaluate the efficacy and safety of ODM-201 in patients with non-metastatic castration (hormone)-resistant prostate cancer. These patients are at high risk of developing metastatic disease and can be identified due to rapid Prostate Specific Antigen (PSA) increases. Phase II clinical studies of ODM-201 demonstrated it to be efficacious and well-tolerated. Eighty-six percent of patients who had not received earlier chemotherapy or abiraterone (Zytiga) experienced a greater than 50% PSA decrease at week 12 on a dose level of 700 mg twice a day. ODM-201 disrupts a tumor cell’s ability to use testosterone by binding with high affinity to the androgen (testosterone) receptor (AR) protein on cells, thereby inhibiting its cellular function. The AR normally binds to testosterone (which fuels prostate cancer) inside the cell and ushers it into the cell nucleus where it enhances cell growth. ODM-201 has similar activity to the anti-androgen drug enzalutamide.
1) MRI or Ultrasound-Guided Biopsies; 2) Effect of Diet on Prostate Cancer; and, 3) Two Genes Linked to Aggressive Prostate Cancer.bjgabrielsen : June 27, 2014 4:12 am : 2014, Diagnostics, Genetics, Imaging, General Patient Information
1) A recent article was published from the Washington University School of Medicine which compared the results of prostate cancer biopsies as guided by magnetic resonance imaging (MRI) with those obtained via ultrasound guidance. It was concluded that MRI-guided biopsies were more likely to find aggressive tumors than those that rely on ultrasound. For specific details, see the following link.
2) Another article published in Medline Plus, described a Duke University study of the effects of diet and lifestyle on prostate cancer. A diet rich in complex carbohydrates and lower in protein and fat is associated with a 60 percent to 70 percent reduced risk of prostate cancer according to the researchers. In addition, a fiber-filled diet reduced the risk of aggressive prostate cancer by 70 percent to 80 percent. The presence of metabolic syndrome factors also increased the cancer risk. Metabolic syndrome consists of a group of risk factors that increase a person’s risk of heart disease, diabetes and stroke. They include obesity, high blood pressure, elevated blood sugar levels, elevated levels of triglycerides (blood fats) and reduced levels of “good” HDL cholesterol.
3) Lastly, Columbia University researchers have identified two genes that they claim “are likely driving the most aggressive cases of prostate cancer. Other scientists had linked the genes, FOXM1 and CENPF, to cancer, but had not connected them to prostate growths. And more importantly, it was observed that the two genes’ cancer-causing effects only occurred if they are turned on at the same time. These two genes individually don’t do anything, or very little, but only when they are co-active do they produce aggressive forms of the disease.” The presence of activity in these two genes could be determined at the time of a biopsy. “If both genes are turned on and highly active, then men would be advised to get immediate treatment such as surgery, radiation or tumor-targeting drugs, or some combination of these. If neither gene, or only one is active, then doctors might recommend less intensive therapy while they monitored the tumors” according to the researchers.
Genomic Health Inc., a cancer diagnostics company, recently announced they are now marketing a genomic test for men diagnosed with prostate cancer that will provide better information on how likely it is that their prostate cancer is an aggressive form of the disease needing immediate treatment, or a slow-growing, low-risk form of prostate cancer that can safely be monitored over time for signs of progression. The new assay, Oncotype DX Prostate Cancer Test, will potentially give tens of thousands of men increased confidence that they can safely forego aggressive treatment and instead enter a program of active surveillance, where their tumor is monitored over time, deferring surgery or radiation and potentially avoiding the sexual and/or bowel and bladder dysfunction side-effects that can result from those treatments. The new test—a 17-gene predictive “signature”, measures the amount of ribonucleic acid (RNA) expressed by these various genes, with some genes making large amounts of RNA and others making little. Seven separate studies by Genomic Health Inc., involving over 1,000 men diagnosed at biopsy with prostate cancer have shown that in men whose tumors turned out to be high-risk, those men tended to test positive for this 17-gene “signature.” The Oncotype DX Prostate Cancer Test currently costs about $3,800 and is not covered by insurances at this time. For further information, please see the following link.