2016 Blog

PSA Testing Do-Overs Recommended

bjgabrielsen : February 21, 2016 7:53 pm : 2016

According to a recent Canadian study, if your doctor suspects you may have prostate cancer because of an elevated prostate-specific antigen (PSA) level, you might want to ask for a repeat PSA test to confirm the results. It could save you from undergoing an unnecessary prostate biopsy that could entail serious complications. Of 1,268 men who underwent a second PSA test within three months of their first test showing elevated PSA levels, 315 (24.8 percent) had normal results the second time around. As a result of their finding, the researchers recommend that men with elevated PSA levels should repeat the test before undergoing a biopsy. The American Urological Association echoes this recommendation. Elevated PSA levels may result from infection, physical activity or sexual activity. Other studies revealed that only 16 to 56 percent of primary care physicians ordered a repeat test for patients with abnormal PSA results. Most experts agree that PSA screening should be used in conjunction with a digital rectal examination, and additional information such as family history, race, and age to assess the likelihood of prostate cancer being present. The information presented here came from the Mayo Clinic Proceedings, published online in December, 2015 and re-printed in HealthAfter50, Scientific American Consumer Health.


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To my readers: Very Important. Hearing from God; Be Still;

bjgabrielsen : February 17, 2016 8:42 pm : 2016

I published a blog on Feb. 17th entitled, “If You Want to Hear from God, Be Still”. This is one of the most important blogs I have written.  The post on the website looks fine but when I received an e mail of it, parts of it were too large and missing. Until I resolve the issue, please go to the original site, http://www.Godandprostate.net, and click on the February 17th post on the homepage. I am linking it here. Sorry for the problem.

 


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If You Want to Hear From God, “Be Still.”

bjgabrielsen : February 17, 2016 7:43 am : 2016
Gulf of Mexico, Boca Grande, Florida; BJ Gabrielsen photo.
Gulf of Mexico, Boca Grande, Florida; BJ Gabrielsen photo.

If you are like me, we often pray to God about our health status, specifically our prostate cancer.  It is indeed an amazing privilege to have that personal relationship with God the Father through faith in His Son, Jesus Christ and be able to bring our needs, anxieties, fears and uncertainties, to God Himself and seek His wisdom, healing, love, security, comfort and specific plans for us.  But how do we hear His response?  If you were seeking advice from a trusted friend, would you simply keep talking without stopping to focus on their response?  The answer is found in Psalm 46:10, “be still” or “cease striving” and “know that I am God.”  The Hebrew word translated “be still” can also be translated “become helpless”, “collapse”, “cease”, “fall limp” and “relax”. The sense is to stop striving.  Personally in my haste to prayerfully communicate my thoughts to God, I have to stop, clear my mind, be silent, shut off external stimulii, and ask God humbly “what would You have me to hear?”  The command to “be still” calls us to totally silence ourselves and listen to God often in the face of great turmoil.  In Psalm 46:1, we are also reminded that God is “our refuge and strength, a very present help in trouble.”  When we learn to practice silence before God, we position ourselves to listen carefully to Him. We purposely quiet ourselves so that we are in a listening mode. We turn away from the constant chatter of our minds and digital world in order to grasp the mysterious ways God speaks to us when we turn our attention fully to Him.

But what of we are not sure if we even have a personal relationship with God?  If I wanted to enter the White House, I’d need to know someone.  In a way, we need a “pass” to obtain entry into the presence of a holy God.  Not one of us is good enough on our own to do so.  He is perfectly holy and righteous and perfectly just in all He does.  We certainly are not.  But when we accept by faith God’s offer to credit us with Christ’s righteousness, we have a “pass” that allows us to “approach the throne of grace with confidence, so that we may receive mercy and find grace to help us in our time of need” (Hebrews 4:16).  We don’t have to worry about earning that grace; Jesus did it once and for all at the cross.  Do you really want to hear from God personally?  First you need a “pass” and His name is Jesus.  Then express your praise, thanks and needs, and “be still” or otherwise translated “cease striving” and “know that He is God.”

Portions of the above were adapted from two February 16th, 2016 devotionals; “Today in the Word”published by the Moody Bible Institute, Chicago, IL and from “Anchor”, a devotional from Haven Ministries, Riverside, CA. The latter was written by a man currently serving a 6-year Federal prison sentence.


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Us TOO – An International Prostate Cancer Education and Support Network

bjgabrielsen : February 16, 2016 5:07 am : 2016

Us TOO was founded by—and continues to be governed by—people directly affected by prostate cancer. They are a nonprofit established in 1990 that serves as a resource of volunteers with peer-to-peer support and educational materials to help men and their families/caregivers make informed decisions about prostate cancer detection, treatment options and related side effects.  Their website is http://www.ustoo.org/home.


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Surgery May Beat Radiation for Men With Early Stage Prostate Cancer

bjgabrielsen : February 3, 2016 5:49 am : 2016

A new Canadian study has concluded that men with organ-confined prostate cancer are more likely to survive if they have surgery rather than radiation therapy.  The authors of the study analyzed data from 19 previous studies involving 119,000 men with localized cancer.  Findings from fifteen (15) of the studies showed that those who received initial radiation therapy were twice as likely to die from prostate cancer as those who had surgery.  Findings from ten (10) of the studies also showed that men who had radiation therapy were 50% more likely to die sooner of any cause, compared to those who had surgery.   The results of the study analyses were published on Dec. 14th, 2015 in the journal European Urology.

The authors add however that “prostate cancer treatment is never a one-size-fits-all matter.”  There are times when radiation therapy may be more appropriate than surgery so it is vitally important that a patient discusses treatment options with his physician.  It is also noted that radiation is still possible as a secondary treatment after surgery.  So patients have yet another way of combating their cancer if necessary.  In addition, a radiation oncologist pointed out that this review may not have accounted for recent improvements in radiation therapy that could boost patient outcomes.  For an additional reference, see the December 29th edition of Prostate Cancer News Today (linked).


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Prostate Cancer Lesions Accurately Detected by New Imaging Agent

bjgabrielsen : February 2, 2016 6:21 am : 2016

Current tests to initially detect prostate cancer rely on biopsies.  Scans such as bone and CT scans, and choline-11 and acetate-11 PET scans are used to identify sites of cancer metastases.  Researchers at Thomas Jefferson University have now developed a new imaging technique to detect prostate cancer cells and malignant lesions.  Their technique is both highly accurate and more effective than current detection methods.  Details of their imaging technique (see link) entitled “VPAC1 Targeted 64Cu-TP3805 Positron Emission Tomography (PET), were recently published in the journal Urology.  The novel copper-peptide (small protein) imaging agent 64Cu-TP3805 attaches itself to VPAC1 receptors on the surface of cancer cells.  The TP3805 peptide portion of the agent hooks on to the cell receptors and the copper-64 radiation-emitting peptide allows their detection by PET-CT scanning.  The technique was tested on 25 prostate cancer patients undergoing radical prostatectomies.  Compared to conventional biopsies, this technique found 105 out of 107 cancerous lesions in the removed prostates as well as nine lesions not found by conventional pathology.  Positive and negative lymph nodes, cases of benign prostatic hyperplasia (BPH), and cysts were also identified.  Larger studies are planned.


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Gleason Score in Diagnosing Prostate Cancer

bjgabrielsen : January 22, 2016 3:32 am : 2016

The following is an excerpt from a January 12th, 2016 blog called Prostate Snatchers by Mark Scholz, M.D.

The latest craze in medical technology is genetic analysis of tumor cells (GAT).  “The scientific progress that has been made with GAT in my opinion is the second most exciting area of advancement in medical technology today (see below for more about the first most exciting area).”  GAT technology is already being commercialized for use in the medical marketplace in products like Prolaris and Oncotype. (For a review of both, see Godanprostate.net November 27,2015 post).  These technologies are able to predict the aggressiveness of prostate cancers, enabling us to differentiate between the men who need immediate treatment and those who can postpone treatment safely.

“The predictive power of GAT is certainly exciting, but there is already an effective form of genetic testing available that has been around for more than 40 years, the Gleason scoring system. The Gleason system relies on the visual appearance of cells under the microscope to draw conclusions about their inner genetic makeup. In the medical world, using the visual appearance of the cancer cells is called phenotypicanalysis. GAT is genotypicanalysis.”

“So how can Gleason score draw conclusions about the underlying genetic potential for tumor aggressiveness simply by looking at the appearance of cells under a microscope?  The answer is to do a comparison of the visual appearance of cancer cells with the appearance of normal prostate cells. Normal cells in the prostate perform varied functions but still work together as a team.  Specifically, healthy cells form into definable structures called glands.  In these glands some cells manufacture prostatic fluid, a complex liquid comprising the ejaculate for the sperm to swim in.  Other cells organize to form ducts, a piping system to drain the fluid from the outer periphery of the gland and channel it into the middle of the prostate so that a large quantity of fluid can be expelled through the urethra at just the right moment.  All of these different cells work as a team and coexist in the prostate functioning together in a structured glandular arrangement.”

“When a trained pathologist looks at tumor cells under the microscope he grades them by the degree of cellular disorder.  He is asking himself the question, ‘How much do these cells retain the normal glandular characteristics of the prostate gland?’  If a cross section of the tumor looks like an unbroken sheet of uniform cells, the cancer is high-grade; the cells have lost their ability to cooperate with each other and form glands. The cancer cells have been honed down into little race cars with only one mission, to aggressively pursue its own replicative destiny. When tumors have this appearance they are graded as a Gleason 9 or 10.  On the other hand, if the appearance of the tumor shows residual glandular components, it is less aggressive, perhaps a Gleason 7.”  Gleason 6 cancer looks almost like normal prostate gland tissue. 

“Predicting future tumor behavior is obviously very important. How fast will it grow?  Is it likely to spread? How well can it be expected to respond to treatment?  As a result of decades of experience, doctors have learned to use the Gleason scoring system to accurately predict the long-term outcome in individual patients. The new GAT tests represent an important additional refinement, further enhancing our ability to predict the future behavior of an individual cancer. GAT holds one even bigger promise.  In the future we believe GAT testing will be a powerful aid in the selection of targeted therapy, i.e., picking cancer treatments with anticancer activity tailored to individual tumor types.  This hope, however, will have to be postponed until our limited armamentarium of effective treatments is further expanded.”

“Now, what is it that I” (Dr. Scholz) “consider to be the most exciting area of medical progress? Since I am an impatient type of guy, someone who is looking for quick results, I find immunotherapy more exciting than GAT. To fully exploit the potential of GAT we will need to invent new pills for each of the myriad of genetically different tumor types. Immunotherapy on the other hand comes with its own ‘built-in’ GAT system that enables it to target the unique genetic signature of individual cancer cells. The immune system is so smart, all we have to do is ‘flip the switch on’ and starts cranking out genetically targeted anticancer therapy. Recent developments in the field of immunology are truly mind-boggling and hold promise for a big revolution in cancer therapy within the next 5-10 years.”


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Aspirin May Cut Prostate Cancer Death Risk; Two Reports;

bjgabrielsen : January 11, 2016 1:10 am : 2016

In a study presented at the January 2016 meeting of the American Society of Clinical Oncology (ASCO), researchers from Harvard’s School of Public Health concluded that “men with prostate cancer who took aspirin regularly after diagnosis had a significantly reduced risk of death.”  Taking aspirin more than three times a week was associated with a 39% lower risk of dying from the disease compared to men who reported less frequent aspirin use.  The study evaluated data from 22,071 men who took part in the Physicians’ Health Study and who were tracked from 1982 to 2009.  Taking aspirin prior to a prostate cancer diagnosis was not shown to be beneficial as “aspirin use did not appear to affect the risk of prostate cancer development or rate of diagnosis.  It also did not affect the frequency of diagnosis of high-grade cancer or locally advanced cancer.  But it was proposed that in addition to its cardiovascular benefits, “regular aspirin use may inhibit lethal prostate cancer possibly by preventing cancer progression.”  Regular use was associated with a 24% lower risk of developing lethal prostate cancer.  It was noted that a recommendation to begin aspirin regimen solely for prevention of lethal prostate cancer is not warranted based on this study alone.  More work is needed to identify the particular subsets of men most likely to benefit from aspirin and to determine the optimal aspirin dose.  It was also learned that the results seen with aspirin did not extrapolate to the use of celebrex.  For more details, see the following link.

 

 

 


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Predicting Prostate Cancer’s Future Behavior

bjgabrielsen : January 8, 2016 5:41 am : 2016

Developing an accurate prognosis, i.e., predicting how a man’s cancer is likely to behave in the future, is the first and most important step toward optimal care. Future predictions are often looked at with some suspicion. With prostate cancer, however, our power to anticipate future cancer behavior is quite accurate unless there is a lack of thoroughness in gathering information.  One system designed to evaluate the risk of prostate cancer recurrence following localized treatment was formulated in 1998 by Dr. Anthony D’Amico.  For a summary of the D’Amico system, see this link.

The Size of the Tumor
Tumor size is a universally important prognostic sign for almost all types of cancer including prostate cancer. The method for incorporating tumor size into the Anthony D’Amico’s staging system relies on the degree of PSA elevation, the tumor grade and on how the prostate “feels” with the finger of a trained practitioner. These indicators are useful but don’t incorporate information from modern imaging. Imaging provides accurate information about tumor size and the presence or absence of extracapsular extension. These are very powerful prognostic predictors and it would be foolish to disregard their importance. As things stand presently these indicators are often used to divide the low, intermediate and high risk D’Amico categories into “favorable” and “unfavorable” subcategories, each with a different spectrum of recommended treatment options.

Knowing Past Treatments Tells Something about Future Prognosis
Historically, since the total number of available treatments is relatively limited, practitioners have used a sequential “trial and error” treatment methodology that administers the standard treatment options in a fairly predictable sequence. For example, it is not uncommon for men to start with surgery or radiation. When a relapse occurs, standard hormone therapy (Lupron) is often started and given intermittently or continuously. Hormone therapy usually controls the disease for an average of 10 years. When Lupron stops working, immunotherapy with Provenge may follow. After Provenge, more potent hormone therapy with Xtandi or Zytiga is started. If these two agents prove ineffective, chemotherapy with Taxotere (docetaxel®) or radiation with Xofigo would be considered next.  The whole point of presenting the treatment sequence described in this paragraph is to convey the idea that the number of previous treatments communicates important information about that patients’ future prognosis. Having “failed” Lupron, for example, bespeaks of a much more worrisome prognosis compared to the situation where Lupron continues to be effective.

Response to Lupron, The Mother of All Metrics
The quality of the “response” to Lupron is actually one of the most powerful prognostic metrics available. The degree of PSA decline after Lupron is incredibly important. How low the PSA drops after starting Lupron is called the “PSA nadir.” The specific PSA threshold used to determine a “good response” is less than 0.1. Believe it or not, there is a huge difference in prognosis between a man on Lupron for six months who has a PSA of 0.1 versus a man whose PSA levels off at 1.0.

An Established History is also a Prognostic Indicator
Another somewhat obvious prognostic indicator that is often overlooked and almost never discussed in textbooks has to do with the prognosis of men who have been diagnosed years ago — over time it is apparent that things are turning out much better than what might have been expected based on their initial indicators. For example, take the case of a man who started off with a panoply of bad indicators—tumor is in the lymph nodes and Gleason 10—but after aggressive treatment remains in remission for 5 years. The fact that things have gone well for five years counts big-time in his favor going forward. Remember, the original prognostic predictors of a Gleason 10 were just that, predictors. No predictor is 100% accurate. Five years of established history is a stronger predictor than the original Gleason score. The fact that things have gone well for five years, strongly indicates that the future is for that individual is bright. Such individuals may have “beaten the odds.”

The Location of the Tumor in the Body
Another extremely important indicator of prognosis, something that even laypeople anticipate by simple common sense, is the location of the cancer in the body. Location says volumes about how things are likely to progress in the future. For example, consider the following sequence of progressively more serious cancer sites:

•Contained within the prostate
•Extended into the seminal vesicle
•Spread to the lymph nodes
•Bone metastases
•Liver metastasis

Each of these locations is very important for determining prognosis.

This short blog is just an introduction to some of the “profiling” methods utilized in generating an accurate prognosis. Space limitations preclude discussion here about other known prognostic factors such as the size of the prostate gland, genetic tests and PSA doubling time. The D’Amico risk categories constitute the backbone of useful prognostic information. However, the additional prognostic information beyond the D’Amico risk categories that are discussed in this blog, provide additional useful information necessary for determining an accurate prognosis. An accurate prognosis is the starting point for accurate selection of treatment.

The preceding blog was posted on Dec 30th, 2015 by Mark Scholz, MD on his site entitled “Prostate Snatchers” to which I recommend a subscription.


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Prostate Cancer Drugs Currently Approved or in Late-stage Clinical Trials.

bjgabrielsen : January 3, 2012 4:49 am : 2012, 2016, 2017

Day’s end in the Gulf of Mexico at Boca Grande, Florida; BJ Gabrielsen

At the time of this writing, there are thirteen (14) drugs currently approved by the Food and Drug Administration for the treatment of prostate cancer. There are others which are in various stages of clinical development or review.  A number of these have been mentioned in earlier blog posts on this website. The National Cancer Institute (NCI) of the National Institutes of Health (NIH) has an excellent website (see also http://www.cancer.gov/cancertopics/types/prostate). A list of approved drugs is also given. Personally, I am finding it helpful to briefly list the drugs discussed in this website with a description of their potential uses and current developmental status. It is my intent to maintain this website listing as current as possible with new additions and developmental updates.

Therapeutic agents already approved by the FDA include:

1 – Lupron (Leuprolide Acetate); used to suppress the production of testosterone in androgen deprivation or hormonal therapy. Leuprolide falls into a class of drugs called luteinizing hormone-releasing hormone (LHRH) agonists. Others drugs in this class include goserelin (Zoladex), triptorelin (Trelstar) and histrelin (Vantas).

2 – Prednisone; used in conjunction with chemotherapy to reduce its potential side effects, inflammation and suppress the body’s immune response.

3 – Taxotere (Docetaxel); a second generation, synthetic taxane drug based upon compounds (Taxol) derived from the European yew tree and used as a potent and broad chemotherapeutic agent. In treating metastatic, hormone-refractory (resistant) prostate cancer, it may be used used in conjunction with other anti-cancer agents and prednisone. Taxotere may be combined with Carboplatin, Xeloda (see below) or Emcyt. It has also been used effectively combined with Avastin and Revlimid.

4 – Jevtana (Cabazitaxel); a new taxane (see taxotere) administered with prednisone and used to treat metastatic, hormone-refractory (resistant) prostate cancer in men who have already undergone chemotherapy. It was approved by the FDA in spring, 2010 for use in metastatic, hormone-resistant prostate cancer patients who have failed chemotherapy with docetaxel (taxotere). (Discussed in the May 7th, 2011 blog post and see http://www.cancer.gov/clinicaltrials/results/cabazitaxel0310).

5 – Zytiga (Abiraterone acetate); This once-daily, oral drug from Johnson & Johnson was approved in April, 2011 for use in men with metastatic, hormone-refractory prostate cancer who have failed docetaxel (taxotere) chemotherapy. Zytiga inhibits two distinct steps in the production of testosterone from cholesterol even in tumor cells themselves by blocking a cell membrane enzyme called CYP17A1.  Inhibiting one step (lyase) in the testosterone production accounts for the drug’s efficacy but inhibiting the other step (hydroxylase) leads to its side effects. (Therefore it might be advantageous to find a drug that would inhibit only the step that accounts for the undesirable side effects). Zytiga is co-administered with prednisone. For additional information, see Wikipedia.  (Discussed in Jan. 8th, May 7th, June 3rd, and Nov. 21st, 2011 blog posts).

6 – Provenge (Sipuleucel-T); an immunotherapy developed by Dendreon and approved in 2011 by the FDA for treatment of asymptomatic or minimally-symptomatic, metastatic, hormone-refractory prostate cancer. It works by inducing an immune response by activated T-cells in a patient’s immune system against a protein called Prostatic Acid Phosphatase (PAP) which is produced in 95% of all prostate cancers. For a review, see http://www.provenge.com. (Discussed in June 3rd and Sept. 20th, 2011 blog posts).

7 – Xgeva (Denosumab); An injectable, monoclonal antibody approved by the FDA to prevent bone fractures and other skeletal events. In 2010, it was originally approved only in prostate cancer patients undergoing hormonal therapy whose cancers had metastasized to bone. In 2011, its approved use was expanded to include patients with no bone metastases. (Discussed in the October 8th, 2011 blog post).®prostatic hyperplasia (BPH). It works by inhibiting an enzyme called 5-alpha reductase which converts testosterone to its more potent form, dihydrotestosterone (DHT) which is ten (10) times more powerful than testosterone for driving the growth of advanced prostate cancer. (Discussed in the Feb. 25th, 2011 blog post).

9 – Xtandi® (enzalutamide, formerly MDV3100); Approved by the FDA on August 30th, 2012 and Sept. 2014 for treatment of metastatic, hormone refractory prostate cancer patients who have either failed chemotherapy such as taxotere (docetaxel) or who have never have had chemotherapy.  Xtandi disrupts tumor cells’ ability to use testosterone by blocking the cell’s testosterone receptors and prevents the production of androgens within the cell itself. It is an oral, androgen receptor antagonist and does not require co-administration of steroids such as prednisone. It was developed and is distributed by Medivation Inc. (San Francisco, CA) and Astellas Pharma Inc. (Japan). For more information, see the blog posts dated September 14th, 2012 and earlier, viz., June 9th, 2012,  Feb. 10th, 2012, Nov. 21st, 2011, May 7th, 2011 and June 19th, 2014.

10 – Xofigo (previously known as alpharadin); Approved on May 15th, 2013 by the U.S. Food and Drug Administration for use in men with treatment-resistant prostate cancer that had metastasized to bones but not to other organs. Xofigo, administered by injection, will be marketed by Bayer Healthcare Pharmaceuticals who developed the therapy jointly with Algeta, ASA, a Norwegian pharmaceutical company. The drug works by delivering radioactive alpha particles directly to prostate cancer cells that have formed tumors in bone. The radioactive alpha particles from radium-223 dichloride are relatively “heavy” and therefore do not penetrate very far in the body thus limiting the effect of the drug to about a 10-cell radius thereby limiting its toxicity. The drug binds with minerals in the bone to deliver radiation directly to the bones limiting damage to surrounding tissues. For further information, see the June 3rd, 2013 blog post or http://xofigo-us.com. Earlier information can be found in the blog posts dated Nov. 5th, 2011 and Feb. 10th, 2012.

Therapeutic agents not yet approved but under clinical development include:

1 – Ipilimumab; (also known as MDX-101 and MDX-010 and marketed as Yervoy) is a human monoclonal antibody developed by Bristol-Myers-Squibb and approved for the treatment of melanoma. It recently failed to show a response in locally advanced prostate cancer (see April 11th, 2017 blog). It is currently undergoing clinical trials in metastatic, hormone-refractory prostate cancer among other cancers. It works by activating a patient’s own immune system by causing cytotoxic T-lymphocytes to potentially combat tumor cells. (See June 3rd, 2011 blog post.)

2 – Capozatinib (XL184); Exelexis’ drug XL184 has already been approved by the FDA for the treatment of certain thyroid cancers. Phase II clinical trial results showed a decrease in metastatic bone lesions and pain in metastatic, hormone-refractory prostate cancer patients. XL184 inhibits an enzyme called tyrosine kinase which is involved in tumor cell proliferation and invasion, growth of new blood vessels (angiogenesis) and bone metastasis among other processes. Phase III trials are on-going in men who are resistant to Zytiga and Taxotere. These trials will evaluate the control of pain and effects on survival. Preliminary studies of XL184 have shown rapid resolution of pain and rapid disappearance of cancer abnormalities seen in bone scans. (See June 3rd, 2011 blog post).

3 – Orteronel (TAK-700); Clinical development has been discontinued. See July 12th, 2014 post. TAK-700 is a selective, oral, non-steroidal androgen synthesis inhibitor which results in lowering testosterone levels by a mechanism similar to that of Zytiga (abiraterone); it inhibits the enzyme CYP17A1. It is currently in Phase III clinical trials sponsored by Millenium and Takeda Pharmaceutical in metastatic, hormone-refractory prostate cancer patients irrespective of whether they have received chemotherapy with docetaxel (taxotere). (See May 7th, June 3rd, and Nov. 21st, 2011 blog posts). See also Wikipedia.

4 – Prostvac (ARN-509); A therapeutic pox-virus vaccine originally formulated at the National Cancer Institute (NCI) and being developed in collaboration with Bavarian-Nordic A/S. It stimulates the immune system to attack cancerous, PSA-producing cells. It is currently in Phase III clinical trials (PROSPECT, initiated in November 2011) in asymptomatic or minimally-symptomatic, hormone-resistant patients. There is considerable interest in administering Prostvac to patients in earlier stages of disease. It is available in clinical trials. (See Sept. 20th blog post and http://www.bavarian-nordic.com/pipeline/prostvac.aspx).

5 – Galeterone (TOK-011); Discontinued development 8/1/2016; Phase III trials discontinued since drug did not meet its endpoints; see link. In Phase III clinical trials for hormone-resistant prostate cancers. It is being developed by Tokai Pharmaceuticals Inc.  Additional information is  now included in a blog posted on January 6th, 2013. Galeterone, an oral drug also known as TOK-011, is unique in that it is the first and only single-agent therapeutic that combines three distinct approaches to attack prostate cancer and which thereby may help to prevent resistance to ADT. Galeterone works by blocking testosterone synthesis (specifically by blocking the enzyme CYP17 lyase), blocking testosterone’s ability to bind to its androgen receptor and finally, by limiting overall androgen receptor levels in the body. Galeterone’s development and review has received a “fast-track designation” by the U.S. Food and Drug Administration.  For additional information, see the January 6th, 2013 blog and the references therein as well as Wikipedia.

6 – Custirsen (OGX-011); Failed to improve overall survival in advanced cancer patients. See Sept. 4th, 2016 blog. Custirsen is designed to block production of clusterin, a cell survival protein that is over-produced in several cancer types of cancer and in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Custirsen is an “antisense drug” which short-circuits the production of necessary proteins in a cell thus killing it. The technology is based on using short pieces of single-stranded RNA to bind to a cell’s messenger RNA (mRNA) which is the molecule responsible for shuttling protein-making instructions from DNA in the cell’s nucleus to the ribosome, the cell’s protein manufacturer. Custirsen is in Phase III clinical trials in combination with Jevtana and also in a separate trial (Synergy) in combination with chemotherapy in patients for hormone-resistant prostate cancer.  For further information, see the OncoGeneX website. See also the March 26th, 2012 website entries in the 2012 blog section.

7 – OGX-427: Another drug under development by OncoGeneX. OGX-427 is a second generation antisense drug which, in preclinical experiments, inhibits production of Heat Shock Protein 27 (Hsp27), a cell survival protein found at elevated levels in many human cancers. The Phase II development program for OGX-427 aims to demonstrate inhibition of Hsp27 can lead to improved prognosis and treatment outcomes for cancer patients. For further information, see the OncoGeneX website. See also the March 26th, 2012 website entries in the 2012 blog section.

8 – BIND-014: A nanoparticle delivery system for taxotere (docetaxel) currently in Phase II clinical trials in men with metastatic, treatment-resistant prostate cancer and non-small cell lung cancer. BIND-014 is being developed by BIND Therapeutics of Cambridge, MA. It is described in the December 5th, 2013 blog.

9- Tasquinimod, or TASQ (ABR-215050), is an oral experimental treatment for men with metastatic, treatment-resistant prostate cancer. Chemically, TASQ is a quinoline-3-carboxamide with three-pronged immunomodulatory (activates the body’s immune system to fight cancer), anti-angiogenic (prevents the formation of new blood vessels to feed tumor cells) and anti-metastatic (inhibiting tumor growth) activity. After completing Phase I and II clinical trials, Active Biotech and Ispen, the drug’s developers, announced successful enrollment of 1,200 patients in 250 clinics for a global, randomized, double-blind, placebo-controlled Phase III clinical trial evaluating TASQ in men with metastatic, hormone-refractory prostate cancer. For additional information, see the January 6th, 2013 blog post and the references therein.

10- ODM-201 is currently recruiting patients in a Phase III clinical trial (ARAMIS) in men with non-metastatic, hormone-resistant prostate cancer. It is being jointly developed by Orion and Bayer Pharmaceuticals. It is an oral, androgen receptor antagonist whose mechanism of action is similar to enzalutamide (above). For more information, see the July 7th, 2014 blog and the February 13th, 2017 blog.

11- Fexapotide triflutate; (NX-1207); NX-1207 is a novel drug under development by Nymox Pharmaceutical targeting patients with localized prostate cancer such as those under active surveillance. It can be injected directly into the prostate by a urologist in an office procedure that takes a few minutes, does not require any type of anesthesia or catheterization, and involves little or no pain or discomfort. It is currently in Phase 2 clinical trials. See the following link for more information.

12- Topsalysin; (PRX302); This drug being developed by Sophiris Bio. targets patients with BPH or low- to intermediate risk prostate cancer. PRX302 is a modified recombinant protein engineered to be selectively activated by an enzyme in the prostate, leading to localized cell death and tissue disruption without damaging neighboring tissue and nerves. PRX302 binds to the GPI-anchored receptors on the surface of prostate cells. Once activated by PSA, a protein produced by normal and cancerous prostate cells, PRX302 combines with other activated PRX302 molecules to form stable transmembrane pores that induce cell death. Prostate-specific activation of PRX302 by enzymatically active PSA thus limits exposure of non-prostate tissues to the drug’s activity, the company reports, contributing to the therapy’s safety. It is currently in Phase 2 trials. See the following link.

13- Olaparib: The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to olaparib (Lynparza), an oral poly ADP-ribose polymerase (PARP) inhibitor, for monotherapy treatment of BRCA1/2 or ATM gene mutated metastatic hormone-resistant prostate cancer in patients who received a prior taxane-based chemotherapy and at least one newer hormonal agent.

This list represents a work-in-progress. The reader is urged to seek the latest additional information concerning these agents by inserting their drug names on the various available search engines such as Google, Wikipedia and websites such as that of the National Cancer Institute (http://www.cancer.gov/cancertopics/types/prostate). Additional information including available clinical trials can be obtained from the company websites developing the drugs.


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