Category: General Patient Information
Phase 2 Clinical Trial Demonstrates Benefits of Metformin in Prostate Cancer.
In a study published in the January 4th, 2014 issue of the journal, European Urology, Swiss researchers found that treatment with the anti-diabetic drug metformin in patients with hormone-resistant prostate cancer increased their progression-free survival and prolonged PSA doubling time. The one-year study included 44 men who were given 1,000 mg (1 gram) of metformin twice daily. After 12 weeks of treatment, 36% of patients were progression-free with over 25% of these men remaining progression-free at 24 weeks. Over 52% of the patients experienced a prolongation of PSA doubling time reflecting slower tumor growth. Additionally, insulin sensitivity markers improved by 26% in the first 12 weeks of treatment. The researchers concluded that treatment with metformin is safe in non-diabetic patients. Metformin’s low cost, favorable toxicity profile and positive effect on metabolic parameters warrants further investigation as a treatment for prostate cancer.
Coffee, Caffeine, PSA Velocity and Hormonal Therapy.
As we have come to expect, the Johns Hopkins Medicine Health Alerts always contain useful information for prostate cancer patients. For example, the January 19th, 2014 issue contained a primer describing the basic concepts and rationale of hormonal therapy. The February 9th edition reported three published studies which link coffee drinking and caffeine to a risk reduction for several types of cancer including aggressive prostate cancer, and its recurrence and progression. Thirdly, the February 16th issue described a study that concluded that PSA velocity (the rate of PSA change over time) “accurately predicted which men would develop prostate cancer and was significantly more accurate than a single PSA measurement in predicting which men would develop aggressive disease.”
1) Financial Assistance for Prostate Cancer (PC) Patients; 2) Three New Commercially-Available Genetic PC Tests; 3) Phase 2 Clinical Trials for Metastatic PC Patients.
1) Payment Assistance for Under Insured Patients. The Patient Access Network (PAN) Foundation offers financial assistance to prostate cancer patients who lack full insurance coverage, allowing access to treatments previously out of reach. In 2012, PAN started an initiative to raise funds to provide castrate-resistant patients access to new and necessary treatments. To date, 2,200 men have enrolled and $22 million in financial assistance has been allocated. Current co-pay programs include treatments involving androgen receptor inhibitors, immunotherapy, radioisotope and metastatic castrate-resistant prostate cancer. Travel assistance for treatments are also available. Application information and details can be found in the November 2013 PCRI Insights.
2) Three new, commercially-available genetic tests for prostate cancer. Prolaris from Myriad Genetics and Oncotype Dx from Genomic Health can help obtain a more accurate measure of tumor aggressiveness. Both tests examine multiple genes in prostate cells that are removed at the time of biopsy. Polaris predicts the risk of ten-year mortality from prostate cancer while Oncotype Dx seeks to more precisely define the risk category of the individual prostate cancer. A third, Confirm MDx from MDxHealth can provide additional assurance that a negative biopsy is truly negative and that the needle did not simply miss the cancer. It is as accurate as a second biopsy without the unwanted complications.
3) Several specific open Phase 2 clinical trials for men with castrate-resistant, metastatic prostate cancer are listed in the November 18th, 2013 PCRI Insights. These trials involve new therapeutic agents such as Provenge, Xofigo and Cabozantinib (XL184). Enrollment information, criteria and locations are found in the Nov. 18th issue.
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Radiation Therapy Meeting Highlights; IMRT Review.
PCRI Insights is published monthly by the Prostate Cancer Research Institute (PCRI) and is must-reading for men with prostate cancer. The November 2013 issue featured a summary of several pertinent abstracts of presentations given at a recent annual meeting of radiation therapists. One abstract presented cure rates achieved with intensity modulated radiation therapy (IMRT) combined with a boost from seed implants. IMRT is a refinement over existing radiotherapy modalities providing for a higher dose of radiation to the tumor while exposing surrounding tissue to less radiation. An excellent review of IMRT has been published in Cancer News. Another study compared the preservation of potency in young men treated with radiation as compared to surgery. A third study and commentary addressed the issue of when radiation therapy should be commenced after PSA relapse. Other abstracts addressed the issue of the timing of the use of hormone blockade accompanying radiation therapy. The final study examined the effect of the rate of PSA doubling on survival rates and times in relapsed prostate cancer patients originally treated with IMRT. Finally, it should be noted that the studies presented here focused on radiation therapy. A man considering treatment for prostate cancer is urged to consider additional modalities before deciding on a specific, personal course of treatment.
Measuring PSA Activity May Be a Better Predictor of Prostate Cancer Aggressiveness.
Research results recently published online in the August 9th issue of The Prostate (Prostate 2013, DOI:10.1002/pros.22714) suggest that measuring the biological enzymatic activity (or lack thereof) of prostate-specific antigen (PSA) could be used as a predictor of prostate cancer (PCa) aggressiveness. As we know, the level of PSA in serum is often used to determine the necessity of prostate biopsies in the diagnosis of prostate cancer. Much research is on-going to discover tests which can be used to measure the aggressiveness of the cancer while at the same time, minimizing the negative side effects often accompanying prostate biopsies. Such a test could also be useful in determining which cancers could be candidates for active surveillance. In a study of 778 surgically-treated prostate cancer patients, a research team from Ohmx Corporation and Northwestern University have found that higher levels of PSA’s enzymatic activity (aPSA) correspond with less aggressive types of PCa (and vice versa). Stated differently, the activity of PSA (aPSA) is inversely proportional to disease stage. “Patients with the most aggressive PCa have significantly reduced PSA activity compared to those with less aggressive disease.” The researchers note that 22% of the men in their study population, namely the diagnosed patients with non-aggressive prostate cancer, could have averted or delayed radical prostatectomy based on their PSA activity findings. Ohmx Corporation is continuing validation studies and developing a commercial test, which they have trademarked PPA (PSA Peptidase Activity). Biochemically, PSA (a protein) is an androgen (hormone) – regulated serine protease enzyme produced by both prostate epithelial and prostate cancer cells. PSA is the major protein found in semen. It is secreted into the prostatic ducts in an inactive form that is then activated biochemically. PSA that enters the circulation is rapidly “bound” although a fraction is inactivated and circulates as “free PSA”. High PSA levels may be predictive of advanced PCa but a large fraction of organ-confined cancers show much lower PSA values that overlap those levels found in men without PCa. Measurement of free versus total PSA can increase specificity for PCa. PSA is also used widely to monitor responses to therapy and is under investigation as a therapeutic target itself. Remember to always discuss these issues with your physician before taking any actions.
But more importantly, whatever your current situation, if you are concerned about prostate cancer either personally or for someone else, remember that God Himself has a message for you. David writes in Psalm 55:22, “Cast your burden upon the Lord and He will sustain you; He will never allow the righteous to be shaken.” In addition, Psalm 34:19 states “many are the afflictions of the righteous; but the Lord delivers him out of them all.”
Johns Hopkins Urology: A Valuable Resource for Prostate Cancer Information.
The Department of Urology at the Johns Hopkins Hospital in Baltimore, Maryland has consistently been rated best (#1) in the annual survey published in U.S. News and World Report. Hopkins urologists provide an excellent source of prostate information via a number of publications. Recent examples are as follows. The July 28th-Aug. 3rd issue of the Johns Hopkins Health Alerts contained an article describing new therapies for men with metastatic, castrate-resistant (hormone-refractory) prostate cancer. Recently approved drugs, which inhibit testosterone and its biological activity, include abiraterone acetate (Zytiga) and enzalutamide (Xtandi). These agents, in addition to the earlier-approved treatments Provenge and Jevtana, provide new options for men with advanced prostate cancer. The Aug. 4th-Aug. 10th issue featured a discussion on diet and prostate cancer. Regular intake of vegetables, especially cruciferous vegetables such as broccoli (containing the active compound sulforaphane) and cabbage, soy foods and lycopene-rich tomato products, have all been associated with a lower risk of prostate cancer. In addition, pomegranate and its juice may slow prostate cancer progression. The same issue discussed the effect of diabetes and its association with aggressive prostate cancer. The most recent weekly issue of the Johns Hopkins Health Alerts (Aug. 18th-24th) featured an article discussing possible help in reducing hot flashes, an undesirable side effect often experienced by men receiving androgen deprivation (hormonal) therapy. A reader can subscribe to automatically receive these Health Alerts electronically for specific conditions such as prostate cancer. Finally, a comprehensive treatise entitled “Prostate Cancer Outlook 2013” written by the Hopkins physicians describing the latest developments in their own specialties, is available for purchase as an invaluable reference.
PSA Velocity, Questions to Ask Your Doctor, Nanoparticle Drug Delivery and Xofigo Review and Video.
I come across numerous smaller articles of interest related to prostate cancer. Rather than summarizing them in separate blog posts, I’d like to send this short list of four. Hopefully, one or more will be of interest to you.
1) On June 5th, 2013, the Johns Hopkins Health Alerts published a short article entitled “What We Can Learn by Measuring PSA Velocity.” It addresses the role of the rate of PSA change in prostate cancer diagnostics, progression, treatment and outcomes.
2) The Prostate Cancer Foundation (PCF) has published a free pamphlet entitled “Questions to Ask Your Doctor About Prostate Cancer.” The pamphlet also contains spaces to fill in the answers to such important questions. See the following link.
3) Xofigo (alpha-radin, radium-223 chloride) was approved in 2013 to treat men with metastatic prostate cancer which had spread to the bone. Results from a recent study demonstrating improved survival and better quality of life were published in the New England Journal of Medicine with an accompanying video describing the drug. See the following link to the July 31st issue of the Prostate Cancer Foundation NewsPulse.
4) Nanoparticles are chemical species which can serve as a targeted delivery system for drugs, proteins and other therapeutics. The drug to be delivered is contained within the nanoparticle whose surface is then coated with targeting moieties such as antibodies. The overall result is the delivery of a specific drug directly to the cancer cells thereby allowing for higher localized doses and minimized systemic side effects. This type of delivery system for docetaxel (taxotere) is given as an example in a video and accompanying article from the July 31st Prostate Cancer Foundation (PCF) NewsPulse. Docetaxel is a chemotherapy used in metastatic, hormone-refractory prostate cancer patients. While it is efficacious, it also can produce serious side effects. It is also limited in the amount of drug which can be administered intravenously. Therefore, nanoparticle delivery can be much more efficacious.
Fish Oil and Prostate Cancer; the Other Side of the Story.
I was watching my usual TV news channels when a story was presented citing a recent study from the Fred Hutchinson Cancer Reseach Center in Seattle and published on-line in the Journal of the National Cancer Institute. The study results seemed to conclude that taking fish oil supplements or eating too much fatty fish, thereby producing higher serum levels of omega-3 fatty acids, may be linked to an increased risk of prostate cancer. Every TV news story included commentary from the news organization’s resident “medical expert” who unanimously concluded that they would now recommend limiting a man’s input of fish oil and fish itself even though health benefits from essential fats like the omega-3 fatty acids from fish and fish oil and the omega-6 fatty acids from olive oil etc. are well known. However, the benefits of excessive omega-3 supplementation was now being called into question. While fish oil does indeed have an anti-inflammatory effect, the study researchers could not offer a biological reason for this link with prostate cancer and called for more studies. The study analyzed levels of omega-3 fatty acids found to a larger degree in some fish in the blood levels of 834 men who had developed prostate cancer and compared these blood levels to 1,393 men with respect to age and race who had not developed cancer. Men who had the highest levels of omega-3 fatty acids had a 43% increase in risk for prostate cancer and a 71% increase in risk for high-grade prostate cancer most likely to be fatal. The highest blood levels of three omega-3 fatty acids (EPA, DPA and DHA) were consistent with taking fish oil supplements or eating at least three servings of fish per week. The men with the highest levels were the most likely to eventually be diagnosed with prostate cancer. These studies are far from clear and a biological basis for these findings is being sought. Earlier, similar studies in a large trial called SELECT had found that taking vitamin E supplements actually increased the risk for prostate cancer. There is another side to this story which did not appear on my TV news channels. The Prostate Cancer Research Institute (PCRI) recently summarized the comments of three well-known prostate cancer researcher-physicians who unanimously differed in their interpretation of these study results. The physicians include Dr. Anthony D’Amico of Harvard and Brigham and Women’s Hospital in Boston, Dr. Mark Moyad and Dr. Charles Myers. The accompanying link also contains a summary of the original study as well as the physicians’ specific comments and critiques. I suggest that you read their comments, and discuss them with your personal prostate cancer physician before making any changes in your dietary and nutritional habits. The opposing viewpoints were not presented on any of the major news channels to my viewing knowledge.
Guard Against Osteoporosis When On Androgen-Deprivation (Hormonal) Therapy.
I recently learned of a good friend who has asymptomatic but metastatic prostate cancer which was being controlled by intermittent androgen deprivation (hormonal) therapy. One of the potential side effects of such therapy is the risk of osteopenia and the more serious condition, osteoporosis. Osteoporosis and the processes involved in breaking down bone (resorption) by cells called osteoclasts and generating new bone from osteoblasts are described clearly and briefly in the April 6th, 2013 issue of the Johns Hopkins Hospital Health Alerts. Patients on hormonal therapy are advised to have annual bone density tests known as dexa scans wherein bone density is measured in the lumbar spine and the hip femoral neck. Such patients also usually take bisphosphonates such as Boniva or Fosamax among others to minimize the bone depletion which often accompanies hormonal therapy. Since bisphosphonates also have some potential side effects coinciding with their long term use, my friend was advised not to take bisphosphonates (specifically Boniva) for a year and observe any effect on his bone density. After one year, the dexa scan showed a dramatic and very significant reduction in his bone density especially in the lumbar spine. He was then placed on a relatively new medication called Prolia (formerly called denosumab) which had been approved in 2011 by the U.S. Food and Drug Administration for use in prostate cancer patients whose cancer had not yet metastasized to bone in addition to other cancer patients.
Prolia works differently from the class of bisphosphonates such as Boniva by specifically binding to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Prolia thereby prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of this RANKL/RANK interaction thereby inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength. Prolia is administered as a 6-month. sub-cutaneous injection.
The moral of this anecdote is that prostate cancer patients undergoing androgen deprivation (hormonal) therapy need to consistently monitor and maintain their bone densities using appropriate medications such as bisphosphonates or Prolia and should also engage in regular exercise regimens to maintain bone strength.