TAK-700 (Ortoronel) and Phase 3 clinical trials

The drug, TAK-700 (Ortoronel) and Phase 3 clinical trials have been described in a blog published on this website on June 3rd, 2011. TAK-700 is an oral, non-steroidal, androgen (e.g. testosterone) synthesis inhibitor. It is being developed by the Takeda Oncology Company affiliated with Millennium. They are sponsoring safety and efficacy clinical trials in men with metastatic prostate cancer who have not had previous chemotherapy or who have had chemotherapy more than two years earlier for early-stage prostate cancer (elm pc004) or metastatic cancer who have received chemotherapy (elm pc005). The trials are evaluating the safety and efficacy of TAK-700 when combined with prednisone as compared with prednisone alone. End points of the study are delay in disease progression and increased survival times.

Prostatesnatchers: A Must-Read Website.

Not long ago, I came across a website called Prostatesnatchers, written by a prominent West coast urologist, Dr. Mark Scholz and Ralph Blum.  Recent posts addressed such topics as:  a) radiation for PSA-relapsed prostate cancer; an alternative to lifelong Lupron (hormonal therapy), Dec. 10th; b) aspirin lowers cancer mortality rates (Nov. 12th); and, c)  how to find a skilled specialist when prostate cancer is suspected (Nov. 5th).  Pertinent e mail blogs are sent every 2-3 weeks or so.   To subscribe to the site, go to prostatesnatchers. blogspot.com and provide your e mail information.

Christmas and New Year thoughts

Display from Lettuce Lake, Arcadia, Florida
Display from Lettuce Lake, Arcadia, Florida

It’s Christmas 2014 and a New Year 2015!!!  The time of year when a man’s thoughts turn to prostate cancer, right?  Unfortunately, it seems that is true for those of us who have this condition.  Just recently, I saw an interview with retiring U.S. Senator Tom Coburn of Oklahoma who is currently undergoing chemotherapy and radiation for advanced prostate cancer.  I also recently noted the death of the former “infamous” Washington D.C. mayor Marion Barry, also a prostate cancer victim with whom I walked the halls of Johns Hopkins Hospital in late 1995.  He was a patient in an adjacent room and was always very congenial during our hallway conversations.  But Christmas is a season of gift giving and most gifts are delivered in a decorative, attractive wrapping.  The same is true of Jesus whose birth we celebrate at this time and who came to earth as a redemptive gift to rescue us from our sinful selves.  Jesus could have wrapped Himself up in a mind-boggling show of power, lighting up the sky with His presence in a celestial show of glory.  Instead in a humble manger, He “made Himself of no reputation, choosing to wrap Himself up “in the likeness of men.”  He did not replace His deity with humanity but added humanity to His deity.  Jesus, like us, is no stranger to our struggles.  He experienced deep loneliness, betrayal, was publicly shamed, misunderstood and falsely accused before being executed to pay the penalty for our sins.  Even in the humble stable of His birth, He did not cease to be God, but surrendered the independent use of His divine powers and the right to manifest His own glory that He had with God the Father before the world existed.  Jesus had a purpose in life.  He came to show us God’s true nature and to teach us how to live, walk and talk as spiritual people.  But more importantly, He came so that we might have a full, intimate relationship with the Father He knew so well.  Jesus’ purpose was to secure our salvation which He did at the cost of His life.  He came so that we might lay our sins and imperfections down at the foot of the cross. This is Jesus’ gift to us at Christmas.  Jesus is the best gift one could ever receive and when you think of this gift, keep the “wrapping” in mind and don’t discard it.  Remember “God also has highly exalted Him and given Him the name which is above every name, that at the name of Jesus every knee should bow……. and that every tongue should confess that Jesus Christ is Lord, to the glory of God the Father.” (Philippians 2:9-11).  Speaking of names, it should also be noted that Jesus was also given the name “Immanuel” meaning “God with us”.  Imagine His divine and human presence is available to each of us by faith alone.  WHAT A BEAUTIFULLY WRAPPED AND MOST VALUABLE GIFT.  MERRY CHRISTMAS!!!! THANK YOU ALL FOR ALLOWING ME TO SHARE A PORTION OF MY LIFE’S JOURNEY WITH YOU.

(Portions of the above were excerpted from Our Daily Bread devotional, December 22, 2014 written by Dr. Joe Stowell).

Current Clinical Trials in Immunotherapy for Prostate Cancer.

The Prostate Cancer Research Institute (PCRI) has listed four (4) Phase 2 or Phase 3 clinical trials which are currently recruiting patients.  These trials all involve immunotherapeutic agents. The first is a Phase 3 trial of ProstAtak® coupled with standard radiation therapy for localized prostate cancer.  Patients should be newly diagnosed with intermediate to high risk disease, having received less than 6 months of hormonal therapy, and with no metastases or no local treatment.  The trial is recruiting in several states and at institutions such as Johns Hopkins and Walter Reed in Maryland and Memorial Sloan Kettering in New York.  Second, a Phase 2 study involving Ipilimumab (Yervoy®) with abiraterone acetate (Zytiga®) plus prednisone in chemotherapy and immunotherapy-naïve patients with progressive metastatic hormone-resistant prostate cancer is recruiting patients at Memorial Sloan Kettering in New York.  Ipilimumab is a human monoclonal antibody currently approved for the treatment of melanoma.  Third, another Phase 2 study involving Provenge® (Sipuleucel-T) coupled with immediate or delayed CTLA-4 blockade is recruiting in San Francisco.  CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) is a protein receptor found on the surface of T-cells that down-regulates the immune system.  The CTLA-4 receptor acts as an “off” switch for the attack of cancer cells by T-cells.  Hence blocking the CTLA-4 receptor would enhance T-cell anticancer activity.  Finally, a Phase 3 trial (Prospect) involving Prostvac in men with few or no symptoms of metastatic, hormone-resistant prostate cancer is recruiting patients.  This Prospect trial has been described in a previous blog posted on August 5th, 2014.

News from Johns Hopkins on Urinary Incontinence, Kegel Exercises and Familial Prostate Cancer.

Urinary incontinence is a major complication of radical prostatectomy.  According to the November 9th Johns Hopkins Health Alerts (Prostate Disorders), incidence of serious incontinence from surgery at medical centers of excellence is low, around 3% whereas from overall national patient survey data, urinary incontinence is dramatically higher, around 50-60%.  For a clear description of the physiology of urinary incontinence, see the full Hopkins Health Alert.  An earlier issue of the Johns Hopkins Health Alerts (August 24th) described the Kegel exercises which strengthen pelvic floor muscles involved in urination.  These exercises are often prescribed before prostate surgery.

Studies performed on hereditary forms of prostate cancer at Johns Hopkins and the National Cancer Institute have shown that men with one close relative, such as a father or brother, with prostate cancer have a two-fold increase in the risk of developing the disease. If two close relatives are affected, there may be as much as a five-fold increase.  Although a great deal of research has been directed toward the roles of diet and dietary supplements in prostate cancer risk, the results have been inconclusive in terms of hard data.  There is a general consensus that a reduction in the consumption of red meat is associated with lower prostate cancer rates, but the reason is not known.  Cruciferous vegetables, such as broccoli, cabbage, and brussels sprouts, and leafy greens, such as kale and collards, contain compounds that seem to reduce prostate cancer risk.  A compound called lycopene, found in tomatoes and best absorbed from cooked tomatoes (as in sauce), is also thought to be helpful.  For a while, selenium and vitamin E were believed to have a significant effect on the risk of developing prostate cancer, but a large multi-institutional trial failed to show any benefit.  Regardless of diet, prostate health should be monitored at least once a year with a PSA and digital rectal examination. And it is not just the absolute value of the PSA that is important, but also the rate of rise from one year to the next. If the PSA goes up more than 0.5 ng/mL/year, regardless of the absolute value, there is a greater risk that prostate cancer may be developing. Under those circumstances, biopsy should be considered, assuming that there are no other special considerations related to overall health or personal preferences.

Do You Have Anything You’d Like to Discard?

Area of "discarded" zinneas
Area of “discarded” zinneas
"Discarded zinnias"
“Discarded zinnias”


In  our current disposable society, I am sure that we can all think about specific items that we would have no use for or difficult times in our lives that we would rather not re-live.  But the truth is that tough times can eventually mature and grow us and be a blessing while discarded items could be of use to others who would need them.  For readers of this website, prostate cancer could be classified as an item we’d rather discard if we could.  Some time ago, I had planted some zinnias which had bloomed beautifully in my garden but eventually withered and died leaving only a dead stalk, brown leaves and dried flowers which had produced some seeds.  I pulled the dead plants out of the ground and tossed them haphazardly into a wooded lot next to my home.  Several summer weeks went by with their Florida sun and afternoon rain.  One day, I was pleasantly surprised to see a row of multi-colored, fully-blooming zinnias in this vacant, wooded lot.  The dead plants had contained seeds which found their way into the sandy soil, had germinated and now produced beautiful flowers with no help from me.  Discarded yard waste contained the elements of life and eventually produced something of beauty and value.  Prostate cancer is a condition we’d rather discard if we could but even an undesirable condition such as this can possess value and provide blessings if subjected to the proper care and guidance.  The Bible speaks of a similar situation.  In the Old Testament book of Jeremiah 18:1-4, the prophet describes a potter who makes a vessel which is damaged and “spoiled” just as we are who have prostate cancer.  But Jeremiah goes on to say that the potter re-made the clay into a useful vessel which was pleasing to him.  At this point, you might ask of what possible value can one’s prostate cancer serve?  It can lead us into recognizing that we are all “terminal” at one stage of our lives.  Since we are all “eternal beings” with an eventual destination of either heaven or hell, it can lead us into focusing our relationships, thoughts, words and deeds in such as way that they have positive, eternal consequences for us and for those around us.  If we have a personal relationship with God through faith in His Son Jesus Christ, the Master Potter can make us into beautiful vessels for His glory even through our diseases.  Those with whom we come into contact can see that though our bodies may be “damaged”, God’s presence in our lives can shine through and we can be pleasing vessels to the Lord and to those around us.  It isn’t our efforts but if we submit our bodies to God (Romans 12:1-2),  His re-forming power does the work.  The apostle Paul wrote (2 Cor. 4:7) that “we have this treasure in earthen vessels that the excellence of the power may be of God and not of us.”  Nothing, not even prostate cancer, is unusable in God’s hands.  In conclusion, even a condition that we’d prefer to discard, can produce beautiful, valuable and meaningful results in the hands of the Master Potter just like my zinnias.  For those who do not have a personal relationship with God (the potter), having prostate cancer and its potential negative result can lead us into entering such a relationship and thereby gaining eternal life in an eventual new heaven and a new earth with a new, indestructible body.  If you want to have such a relationship, see the following website section.  Prostate cancer can have positive results.  For related thoughts, see the January, 2011 website post entitled “Don’t Waste Your Cancer”.

Four Experts Recommend the Earlier Use of Provenge in Metastatic Prostate Cancer.

In  the last few years, several new therapeutic agents have been approved for treating various aspects of prostate cancer.  Now research also needs to focus on the timely utilization of these agents either individually or in combination and at which stages of disease should they best be applied.  Provenge® (sipuleucel-T) was approved by the Food and Drug Administration in 2010 for metastatic prostate cancer patients who were hormone-resistant (refractory) and who had little or no pain. Provenge® is an immunotherapy uniquely administered over several weeks and generally acts by “kick starting” the immune system while not attacking cancer cells directly.  This website has described Provenge® in several posts over the past years.  The question of when in the course of prostate cancer treatment should Provenge® optimally be administered is currently under much discussion.  A recent series of video and e mail comments from four prominent prostate cancer physicians propose that Provenge® should be used at an early stage in the treatment of metastatic cancer.  The videos and comments are linked in this post.  The physicians cited are Dr. Charles Myers (himself a prostate cancer survivor), Dr. Charles Drake from Johns Hopkins, Dr. David Crawford from the University of Colorado, and Dr. Leonard Gomella from the Jefferson Kimmel Cancer Center.  The reader is urged to share this information with one’s physician as much of it is medical in nature.  But it raises some interesting points for discussion and possible incorporation into a treatment regimen as directed by one’s individual physician.

1) A “Calculator” to Predict Biopsy Outcomes; 2) Understanding the TNM Staging System Upon Prostate Cancer Diagnosis.

1) Researchers at the University of Texas Health Sciences Center in San Antonio have developed a “calculator” to predict probabilities of biopsy results based upon data such as PSA, age, race, results of digital examination and family history.  To access the “calculator” online, go to http://deb.uthscsa.edu/URORiskCalc/Pages/calcs/jsp.  The “calculator” is based on data from the prostate cancer trial that involved more than 5,800 patients to determine the risk of developing prostate cancer based upon PSA and digital rectal examinations. This information was recently cited in the October 19th Johns Hopkins Prostate Disorder Health Alerts.

2) When prostate cancer is first detected, the urologist will describe the extent of the tumor and the course of the disease using a system called the Whitmore-Jewett method or more commonly the TNM (tumor, nodes, metastasis) staging system.  The “T” value describes the extent of the tumor; the “N” value indicates whether the cancer has spread to any lymph nodes; and, the “M” value indicates the presence or absence of metastasis to distant sites. This description will help in the choice of the most appropriate treatment option. The Johns Hopkins Health Alerts (September 13th, 2014) describes the TNM stages in more detail.

Monitoring Emergence of Treatment-Resistant Prostate Cancer by Measuring Circulating Tumor DNA Levels.

Androgen deprivation (hormonal) therapy is often administered to men with advanced prostate cancer.  However, after a period of time genetic mutations can occur in the prostate cells which then promote tumor growth.  A new way to monitor how a man’s cancer is changing during treatment and which could help identify the stage at which some drugs stop being effective would be very useful.  A new blood test which measures DNA from these circulating prostate cells could reveal when existing treatment stops working and harmful, hormone-resistant tumor cells begin proliferating.  At that point, existing treatment could be stopped and the next best treatment option could be administered.  Measuring the circulating tumor cell’s DNA could conceivably personalize treatment for an individual based on the tumor cell mutations detected.  According to a study published in the September 17th Science Translational Medicine and summarized in the September Prostate Cancer Foundation (PCF) Research NewsPulse, such a test could be a less invasive and less expensive way to monitor the emergence of treatment-resistant prostate cancer.  This published preliminary study was small (16 men) and larger studies are in order.

Recommendations for Men Whose Tumors Have Become Resistant to Hormone Therapy.

Testosterone (androgen)-depleting therapies are usually the first line of defense for men with newly-diagnosed or recurrent prostate cancer. But resistance to these therapies develop over time which leaves the patient and physicians with a number of choices as to the next sequence of therapies to be administered. Recently, guidelines, issued jointly by the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) in Canada, highlight recent advances in treating this more advanced form of prostate cancer. Six new treatments have been approved in the last two years for the treatment of prostate cancer and its symptoms. However, opinions differ as to the sequence of using these therapies and their cost, their relationships to a man’s quality of life, the disease stage of the cancer, and prior therapies received by the patient. Combination studies are certainly needed and underway. The new guidelines for hormone therapy – resistant tumors that have metastasized are based on a review of 56 randomized clinical trials published since 1979 and include the following recommendations.

a) Continue hormone-deprivation therapy indefinitely.                                                              b) In addition to hormone deprivation, offer patients one of three treatment options including Zytiga® (abiraterone acetate and prednisone), Xtandi® (enzalutamide), or alpha-radin (radium-223 chloride if the cancer has spread to the bones). All three treatments are associated with improved survival, quality of life and a favorable balance of benefit and harms.                                                                                                                                c) When considering chemotherapy, taxotere (docetaxel®) with prednisone should be an option but side effects must be discussed. See also the September 20th, 2014 blog.             d) Offer cabazitaxel to men whose disease worsens even if taxotere has been tried,  but again discuss the side effects.                                                                                                             e) Offer Provenge® (sipuleucel-T) to men with no or minimal cancer symptoms. Some physicians maintain that it can be most effective to initially stimulate the immune system with agents like Provenge® before other agents are utilized.                                                      f) Offer mitoxantrone but include a discussion of the drug’s limited clinical benefit and side effect risk. Mitoxantrone is also used to treat leukemias and multiple sclerosis.           g) Offer ketoconazole or the anti-androgen therapies bicalutamide, flutamide or nilutamide but discuss the limited clinical benefits of these three medications.                    h) Do not offer other anti-cancer drugs such as bevacizumab (Avastin®), estramustine or sunitinib.                                                                                                                                                  i) Begin discussions of palliative care early on while discussing treatment options.

The experts on the panel formulating these guidelines said the optimum sequence in which various treatments should be given remains unclear, but “ongoing clinical trials are exploring this question, as well as potential benefits of combining various treatments.”