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When All Means Fail – a message for those in a critical battle with prostate cancer.

David Wilkerson was a famous Christian pastor and spiritual leader. In the 1950’s, he left his relatively rural background in Indiana and Pennsylvania and traveled to New York City to begin working with gang members and drug addicts. Out of that move was born Teen Challenge, a Christian drug and alcohol rehabilitation program which today has grown to 1,000 centers in the United States and in 80 other countries. Rev. Wilkerson’s experiences were depicted in a book, “The Cross and the Switchblade”, which has sold over 50 million copies and has been translated into 30 languages. In 1987, Rev. Wilkerson went on to establish Times Square Church near Broadway in New York City which he pastored for 23 years.  David Wilkerson was suddenly killed in an automobile accident on April 27th, 2011. The following is his personal devotional from that day, April 27th, which can be applied to anyone who is seriously battling prostate cancer. (See http://www.worldchallenge.org/in-memory-of-david-wilkerson/.)

“To believe when all means fail is exceedingly pleasing to God and is most acceptable. Jesus said to Thomas, ‘You have believed because you have seen, but blessed are those who believe and have not seen’ (John 20:29). Blessed are those who believe when there is no evidence of an answer to prayer – who trust beyond hope when all means have failed.

Someone has come to the place of hopelessness – the end of hope – the end of all means. A loved one is facing death and doctors give no hope. Death seems inevitable. Hope is gone. The miracle prayed for is not happening.

That is when Satan’s hordes come to attack your mind with fear, anger and over-whelming questions: ‘Where is your God now? You prayed until you had no tears left. You fasted. You stood on promises. You trusted.’  Blasphemous thoughts will be injected into your mind: ‘Prayer failed. Faith failed. Don’t quit on God – just do not trust him anymore. It doesn’t pay.’ Even questioning God’s existence will be injected into your mind. These have been the devices of Satan for centuries. Some of the godliest men and women who ever lived were under such demonic attacks.

To those going through the valley and shadow of death, hear this word: Weeping will last through some dark, awful nights – and in that darkness you will soon hear the Father whisper, ‘I am with you. I cannot tell you why right now, but one day it will all make sense. You will see it was all part of my plan. It was no accident. It was no failure on your part. Hold fast. Let me embrace you in your hour of pain.’

Beloved, God has never failed to act but in goodness and love. When all means fail – His love prevails. Hold fast to your faith.  Stand fast on His Word. There is no other hope in this world.”

GOOD NEWS!!! New Regimens and Therapeutic Agents in the Pipeline; a Visit with my Oncologist.

Every six months, I have an appointment with my oncologist at the Moffitt Cancer Center, on the campus of the University of South Florida, in Tampa. Moffitt is a designated National Cancer Institute (NCI, National Institutes of Health, my former employer) Comprehensive Cancer Center, a highly-sought-after distinction. My oncologist had been highly recommended to me by former program directors at the National Cancer Institute. I am always grateful for the opportunity to discuss with him not only my own situation but to learn about new potential therapies in various stages of clinical trials.

One such earlier appointment is chronicled in the My Story section of this website, November 25th, 2009. At that time, we had discussed the positive results seen in prostate cancer patients treated with either Provenge or abiraterone. In 2011, both of these drugs have now received FDA approval. This has affected my own prognosis dramatically. When a prostate cancer patient becomes resistant (refractory) to standard hormonal therapy and the cancer metastasizes, the next chemotherapy option is usually taxotere and prednisone. Serious side effects often accompany taxotere / prednisone treatment. I am currently in my 5th year on hormonal therapy and my oncologist informed me that I could be maintained in this non-symptomatic manner for years before I would become refractory. Looking ahead, I did not look forward to chemotherapy with taxotere. But with the availability of new therapies, my own “treatment schedule” had changed. After hormonal therapy, I would probably be placed sequentially on Provenge and/or abiraterone, both of which are effective and well tolerated. All in all, the goal of prostate cancer patients like myself is simply to “buy quality time” unless God chooses to heal us directly (which is always possible). I am now nearly 70 years of age. I just may out-live this disease. God uses many methods and the God-given talents of many people to heal or stabilize our diseases.

To make the situation more optimistic, the following are several new potential therapies in various stages of clinical trials. [For an excellent overview of the various phases (I, II, III) of clinical testing required of a drug to obtain FDA approval, see the Johns Hopkins Health Alert related to prescription drugs,  posted March 10, 2009. Phase I studies focus mainly on biological effects, including harmful side effects of the drug on the human body; Phase II studies attempt to demonstrate whether the drug provides a safe benefit in treating people with a specific condition; and, Phase III studies better define the benefits, risks and side effects of the drug.]

1) As a follow-up to current hormonal (androgen deprivation) therapy, Millennium and its parent company Takeda Pharmaceutical, are developing TAK-700 (future name to be Ortoronel), a selective, oral, non-steroidal androgen synthesis inhibitor. In preclinical studies TAK-700 has been shown to bind to and inhibit the enzyme 17,20-lyase 1 in the testes and adrenal glands. TAK-700 is now in Phase III clinical trials in metastatic, castration-resistant prostate cancer and studies are planned for patients who have failed taxotere as well. For information, see the “New Prostate Cancer Info Link,

2) Another new drug is Exelexis’ capozantinib (XL184) which has already received FDA orphan drug approval for the treatment of certain thyroid cancers.  Optimistic reports for XL 184 came from Phase II clinical trials on patients with metastatic  prostate cancer who had failed hormonal therapy. In a group of patients, 95% achieved complete or partial resolution of metastatic bone lesions. Bone scans taken after treatment could not detect any metastases on patients whose previous scans demonstrated substantial cancer spread. The pain accompanying cancer metastasis to the bone was also alleviated.  While XL184 was well tolerated and demonstrated substantial activity against bone metastases, similar dramatic activity against the primary tumor was observed in only six (6) of the 100 patients. Therefore it is too early to predict whether XL184 will extend survival.  XL184, a member of a class of drugs known as tyrosine kinase inhibitors, is designed to work as follows. In cells, MET (otherwise known as hepatocyte growth factor, HGF) and vascular endothelial growth factor type-2 (VEGF2) are both proteins produced by cells. MET is involved in tumor cell proliferation, invasion and tumor spread as well as bone metastasis; while VEGF-2 stimulates angiogenesis, the growth of new blood vessels to feed the tumors. Drugs like XL184 have the potential to “switch off” processes (initiated by tyrosine kinases) within a cell that promote tumor growth.  MET and VEGF also play roles in the function of healthy bone cells such as osteoblasts and osteoclasts. “Switching off” MET and VEGF  simultaneously may block the progression of bone lesions.  While Phase III trials are planned, phase II trials are still recruiting prostate cancer patients in ten states; see http://www.clinicaltrials.gov/ct2/show/NCT00940225.  XL184 is also being evaluated against other tumors such as ovarian.  (Reference: Dr. Mark Scholz, in PCRI Insights, May, 2011, Vol. 14, No. 2, pp.12-14).

3) A third drug to watch for is Yervoy (previously known as ipilimumab) from Bristol-Myers-Squibb. Yervoy, a human  monoclonal antibody, is a cancer immunotherapy that has previously received FDA approval in March, 2011 to treat melanoma.  The Yervoy antibody targets cytotoxic T lymphocyte antigen-4, preventing the antigen from interacting with its ligands and thereby activating the patient’s own immune system by causing these T-cells to potentially combat tumor cells.  More simply, Yervoy blocks a switch that turns off an anti-tumor cellular response. Therefore, Yervoy is an agent that “blocks a blocker” thereby aiding the immune system to fight the tumor.  It should also be mentioned that nearly 13% of patients taking Yervoy had severe autoimmune reactions, consisting of mostly of fatigue and severe skin and gastrointestinal reactions.  The FDA is allowing Yervoy to be evaluated against prostate cancer.

So You’ve Been Diagnosed With Prostate Cancer!! Now What??

In my case, my initial diagnosis occurred in 1995 when I was 54 years of age. At that time, the only option for me was surgery by the best urologist-surgeon I could find. Since that time, over fifteen years have passed which have yielded volumes of clinical data concerning treatment successes and failures, tumor grades, Gleason scores, survival rates, side effects etc. For many men, “watchful waiting” is now an option to be seriously considered along with surgery. If you have been given a recent diagnosis of prostate cancer, two articles have recently been published in the National Cancer Institute (NCI) Cancer Bulletin which you should share with your physician. The first article entitled “Prostate Cancer Study Provides More Data on Surgery versus Watchful Waiting” was published in the May 17th, 2011 issue (Volume 8, Number 10). The most recent entitled “Study Questions Benefit of Surgery versus Watchful Waiting in Some with Prostate Cancer” appeared as a feature article in the May 31st, 2011 issue (Volume 8, Number 11). While one cannot formulate a general rule for every man regarding the question of surgery versus “watchful waiting”, it may be useful to share this information with your physician / health provider before devising the best strategy for your individual prognosis and treatment plan, if any.  As Dr. Julio Pow-Sang of the Moffitt Cancer Center at the University of South Florida stated, “the bottom line is that treatment of early-stage prostate cancer must be individualized.”

Countering Weight Gain as a Result of Hormonal Therapy.

Benefits and risks accompany virtually every method of treatment. Hormonal therapy for prostate cancer is no exception. Potential risks include osteoporosis and bone fractures, cardiac effects, diabetes, depression, hot flashes and metabolic changes resulting in weight gain. (These issues are discussed on this website under “My Story”, 2009 entries of July 5th-27th, September 29th, October 20th, November 25th, and December 6th, as well as March 12th, 2010.) I have been on continuous or intermittent hormonal therapy since August, 2006. Fortunately, my side effects have been minimal although I had gained approximately fifteen pounds. I was told by a urologist that it was difficult to lose weight while on hormonal therapy. Eventually however, I was determined to lose these unwanted pounds. It has not been easy but I have lost most of the weight while continuing my therapy. I found that once I made up my mind to lose the weight, it was indeed possible with diet and exercise. Here are some practical tips I learned along the way.

Personally, it helped to make an initial investment and enroll in one of the popular advertised weight loss programs. It did not take long to begin to understand their general principles and one could discontinue enrolling after a month or so thus saving money. The diets in general consisted of very low-fat, low-carbohydrate meals with moderate protein content. I found the following strategies to be helpful.

1) Eat a fairly substantial breakfast of whole-grain cereals, fruits and light soy or low-fat milk; eggs (omelets) can be substituted.

2) Eat about 5 small meals a day and eat less as the day progresses. Mid-morning and mid-afternoon 100-calorie snacks (cheese, yogurt, fruit) were useful in curbing hunger.

3) If possible, eat dinner at mid-day and your usual lunch as the evening meal. Low fat meats such as chicken, turkey, lean beef (ground sirloin, lean roast beef) as well as fish become staples. Bread was limited to 1-2 slices of 40-calorie whole grain bread daily. Fresh vegetables and salads with low-fat dressing are of course encouraged. Low-fat mayonnaise is recommended but I personally found that one could never fully replace the flavor of real mayonnaise, so I used it in moderation.

4) Sip on water during the day; drinking an 8 oz. glass before meals helped me eat less while feeling satisfied. Diet drinks can be used but I found that water alone was best in satisfying my hunger.

5) Exercise is a must. Aerobic and weight-bearing exercises are also good for healthy bones. My wife and I exercise for 60 minutes in a gym three-times a week.

6) Minimize the use of alcohol, although a small glass of wine on occasions can be incorporated.

7) To satisfy my salt craving, pretzels seemed to be lowest in calorie content.

8) Don’t eat within three hours of bedtime except for a small piece of fruit or similar low calorie snacks. Midnight snacks are forbidden.

9) The eventual goal is portion control. I found that after a few weeks, my hunger was fully satisfied with 33% less food than I had previously consumed. Maintaining this level remains my goal.

FDA Approves Abiraterone (Zytiga) for Advanced Prostate Cancer

(An initial blog was published on this website on Jan. 8th, 2011, describing results from late stage clinical trials of abiraterone acetate in hormone-refractory prostate cancer patients.)

On April 28th, the Food and Drug Administration (FDA) approved abiraterone (Zytiga) for the treatment of men with metastatic castration (hormone)-resistant prostate cancer (meaning the disease progresses despite low levels of tumor growth-promoting hormones) that are no longer responding to the chemotherapy drug docetaxel (taxotere). It should also be noted that in spring, 2010, the FDA approved cabazitaxel (Jevtana) for the same indication. (Cabazitaxel is a member of a class of drugs based on natural products called taxanes. These were originally isolated and identified from yew plants.) In both cases, the FDA approvals were based on findings from large phase III trials in which both drugs improved patient survival as reported in the National Cancer Institute’s Cancer Bulletin, May 3rd, 2011.

The survival improvements produced by abiraterone and cabazitaxel are meaningful but the benefits are still modest: both drugs improve patients’ median overall survival by approximately 2 to 4 months. One advantage is that abiraterone seemingly has fewer side effects and can be taken orally according to Dr. William Dahut of the National Cancer Institute’s Center for Cancer Research.

In the phase III trial, 1,200 patients were randomly assigned to abiraterone administered  in combination with the steroid prednisone or to prednisone plus placebo. The median survival time was 14.8 months in patients who received abiraterone and prednisone compared to 10.9 months in those receiving prednisone alone. In addition to testosterone, abiraterone affects production of other hormones that can lead to side effects such as hypertension. Therefore steroids like prednisone are used to protect against or minimize such side effects. Steroids can have their own long-term side effects, though, so the need to combine abiraterone with steroids could limit use of abiraterone in men with earlier-stage disease and longer life expectancies.

Abiraterone’s target is the production of testosterone. It works by inhibiting an enzyme, CYP17,  that plays a central role in allowing the body to produce testosterone from cholesterol. However, studies have shown that tumor cells adapt to a low-androgen (such as testosterone) environment, in part by increasing the expression of the androgen receptors on their cell surfaces. So, while the overall amount of testosterone in the body may be very low, it is still being produced, and tumor cells develop the ability to take in as much as they can get. For more information, see the following link to WebMD.

With these newly-approved drugs and several others in clinical trials, more research is needed to determine the best sequence of therapies, or which combination of multiple therapeutic agents might be more effective to benefit the individual patient. In addition to abiraterone, two other drugs, TAK-700 and MDV-3100, are in phase III clinical trials in men with castration (hormone)-resistant prostate cancer that is no longer responding to docetaxel. TAK-700 also targets the production of testosterone but it could potentially be used at doses that would not require concomitant steroid supplementation and the resulting side effects of steroids such as prednisone. MDV3100 works differently, disrupting tumor cells’ ability to use testosterone. It does this in part by clogging up androgen receptors on cells which bind testosterone. Because of its mechanism of action, MDV3100 does not have to be used in combination with steroids.

The overall good news is that newer therapies which perform their functions differently are progressing through the pipeline for use in combating prostate cancer.

Pomegranate Extract Slows PSA Doubling Time.

Cancer researchers led by Dr. Michael Carducci at the Johns Hopkins Hospital in Baltimore, MD recently reported the results from studies funded by POM Wonderful to investigate the potential benefits of their POM-X pomegranate extract. The results were reported at the February 2011 American Society of Clinical Oncology (ASCO) Genitourinary Symposium. PSA doubling time in 104 men taking 1,000 mg or 3,000 mg (milligrams) of the extract increased from a median of 11.9 months before taking POM-X to 18.5 months after taking the extract. “There was no significant treatment difference between the different dosages on PSA doubling.” According to a recent article in the March 2011 issue of the Prostate Cancer Research Institute (PCRI) Insights (Vol. 14, No.1, http://www.prostate-cancer.org/pcricms/node/59), “This implies that cancer growth is slowed. It is hoped (but not yet proven) that doubling times induced by POM-X will result in longer time to progression and improved lives for men with prostate cancer.”

This study reinforces a smaller 2005-6 study at UCLA wherein men drinking 8 oz. daily of POM Wonderful pomegranate juice experienced longer PSA doubling times. A research group led by Dr. Manuela Martins-Green had determined that pomegranate juice concentrate increased cell death in prostate tumor cell lines that were resistant to testosterone (which are associated with metastasis), increased cell adhesion and decreased migration in prostate cancer cells that survived. More recently, it was reported at the American Society for Cell Biology’s December 12th, 2010 meeting that specific families of chemical compounds isolated and identified from the pomegranate extract inhibited the migration of cancer cells and their attraction to a signal that promotes metastasis to the bone.

Neither of these above studies had a placebo arm so it is not unequivocally proven that the pomegranate actually caused the improvement. One can read about this study and others in the PCRI Insights Newsletter (see below). One such example is “Pomegranates and Prostate Health: A Research Report” available at http://www.prostate-cancer.org/pcricms/node/112.  The useful PCRI Insights are also available by mail. Their contact information is 5777 West Century Blvd. Suite 800, Los Angeles, CA 90045; phone: (310) 743-2116; helpline: (310) 743-2110; e mail: pcri@pcri.org; web address: www.prostate-cancer.org and www.pcri.org.

As always, material on this website is presented for information purposes only. Significant interactions between natural food products and various medications are possible. The reader is urged to consult their health professional before using any new substances or products.

PSA Velocity Does not Improve Prostate Cancer Detection

One of the major issues for men who are being screened for prostate cancer is whether or not to undergo a prostate needle biopsy. Factors considered in the standard risk model include prostate-specific antigen (PSA) level, digital rectal examination result, age, family history of prostate cancer and history of any prior prostate biopsies. The rate of change in PSA levels with time, referred to as PSA velocity, has also been used as one criterion for determining the need for a prostate biopsy. Clinical recommendations from two organizations, the National Comprehensive Cancer Network (NCCN) and the American Urology Association (AUA), suggest that men with a PSA velocity that exceeds a certain threshold value (0.35 ng/ml per year) should consider having a needle biopsy, even if their overall PSA levels are below the standard cutoff for the procedure and they have a normal result on a digital rectal examination. However, a recent study published online February 24 in the Journal of the National Cancer Institute concluded that a rapid increase in prostate-specific antigen (PSA) levels is not grounds for automatically recommending a prostate biopsy. This study was also summarized in the March 8th, 2011 issue of the National Cancer Institute (NCI) Cancer Bulletin. Researchers looked at whether a PSA velocity above the 0.35 ng/ml per year threshold—when added to a standard risk model that includes age, PSA level, DRE result, family history of prostate cancer, and history of a prior prostate biopsy—improved the model’s predictive accuracy. The authors concluded that “in all cases, the addition of PSA velocity yielded only a slight difference in the risk model’s predictive accuracy. In fact, the analysis indicated that lowering the PSA threshold for a biopsy from 4.0 ng/ml to 2.5 ng/ml would be a more effective means of directing prostate biopsies.”

As always, the content of this website is intended for information use only. All personal medical decisions and actions should be made only after consultation with established medical professionals.

Peace when most needed.

Monday, March 7th, 2011 was my day for my 4-month PSA test in preparation for my urologist appointment next week. In the past, the week leading up to the PSA test had been characterized by periods of mild depression and apprehension. But the intensity and frequency of these episodes had been on the decrease. In fact, as time goes on, I find myself getting more and more trusting and confident in God’s power to maintain my disease. It is a general rule that our trust levels increase in times of stress as opposed to times of tranquility. At the end of our March 6th Sunday church service, my pastor again anointed me with oil and prayed over me in accordance with James 5:14-15. My consistent prayer is that my prostate cancer either be healed completely or that I be kept in natural or medication-induced remission. But I am always being challenged that in addition to my prayer for healing, it should instead be like that of Christ’s prayer before His crucifixion, namely that “not my will but God’s be done.” In any event, as I entered the hospital parking lot on a beautiful sunny Florida Monday afternoon, I paused for a few minutes and meditated upon, prayed and claimed (where appropriate) God’s wonderful promises and wisdom listed in my website section entitled “Spiritual Medicines.” With a resulting sense of peace, tranquility and humble confidence, I entered the hospital and my blood was drawn. The result would be known in 24 hours.

Tuesday morning I awoke with a great deal of apprehension. Would I continue to be in “remission” or would the PSA result show that I had become resistant (refractory) to the hormone treatments? This would be disastrous as it would accelerate my downward disease progression. I could not shake the negative feelings.  I have got to learn to counter these worst-case scenario “what if…” feelings. By noon, I could wait no longer and called my urologist who informed me that my PSA again was <0.02 ng/mL or basically undetectable. Halleluia!!! On the phone I exclaimed “praise the name of Jesus” in response to the congratulatory voices from my urologist’s office. God is so good!!!! I now await my next Lupron treatment or perhaps a “holiday”???? I will have been on hormonal therapy for five (5) years this coming July, 2011. My most troubling side effect has been a fifteen pound weight gain which I am attempting to lose by a strict diet and weight-bearing and aerobic exercise several times per week. My goal is to lose twelve (12) pounds. I’ll let you know if I succeed.

Avodart (dutasteride) used to treat benign prostatic hyperplasia (BPH) may slow the growth of early-stage prostate cancer

A recent study presented on Feb. 17-19th  at the 2011 Genitourinary Cancers Symposium in Orlando, FL by researchers from the University Health Network in Toronto, Canada concluded that for men who are undergoing “watchful-waiting” for prostate cancer, Avodart could help control the disease and prevent the need for more aggressive treatments. “Watchful waiting,” or active-surveillance refers to the practice of foregoing immediate treatment after a prostate cancer diagnosis in favor of regularly-scheduled testing and clinical exams to closely monitor the disease.

Avodart (dutasteride) is already approved by the Food and Drug Administration (FDA) for the treatment of an enlarged prostate gland, or benign prostatic hyperplasia (BPH). The drug inhibits an enzyme called 5-alpha reductase, which converts testosterone into its more potent form, dihydrotestosterone. In addition to BPH, 5-alpha reductase drugs are also used to treat prostate cancer and baldness. Further details from the study can be found in the Feb. 22, 2011 issue of the National Cancer Institute (NCI) Cancer Bulletin. ”In the dutasteride group, 38 percent of the 302 men enrolled in the study experienced some progression of their cancer, compared with 49 percent of the men in the placebo (control) group. This difference translated into a reduction of relative risk for cancer progression of 38.9 percent in the dutasteride group. In addition, taking dutasteride increased the chances that no cancer would be found during a participant’s final biopsy. Thirty-six percent of the men in the dutasteride group and 23 percent of the men in the placebo group had no cancer detected in their final biopsy specimens.” The researchers suggested that it could be “very reasonable” to give a 5-alpha reductase inhibitor such as dutasteride to patients with “ultra low-risk” prostate cancer who elect for “watchful waiting”. It was also noted that the FDA’s Oncologic Drugs Advisory Committee had previously rejected GlaxoSmithKline’s application for dutasteride for use in preventing prostate cancer.

A word of caution regarding the Avodart study described above was recently published on March 9th in the Johns Hopkins Health Alerts: Prostate Disorders. The Hopkins physicians stated that it was unclear whether Avodart actually prevents prostate tumors or simply reduces the chance of a diagnosis. They noted that in the above study, “more people in the placebo group than in the Avodart group received a diagnosis of prostate cancer during the four-year study: 25% versus 20%.  While these findings may sound like good news, it’s possible that Avodart simply suppressed PSA levels, rather than preventing the development of new cancers. Another concern: More men in the Avodart group than in the placebo group were diagnosed with a tumor with a high Gleason score — the tumors most likely to be lethal. ” The Johns Hopkins physicians advised that “if you take Avodart for any reason, be sure that the doctor who performs your PSA screening test is aware of this information. Because Avodart may simply be suppressing your PSA level, he or she will need to perform a mathematical calculation to determine your “true” level. “

Promising results for the late-stage prostate cancer drug, MDV3100.

MDV 3100 is a promising new treatment under clinical development by Medivation, Inc. and Astellas Pharma Inc. for advanced prostate cancer patients who have already received chemotherapy with taxotere (docetaxel) as well as those who have not been treated with taxotere.  MDV3100 slows growth and induces cell death in bicalutamide (casodex)-resistant cancers via three complementary actions.  MDV3100 blocks testosterone binding to the androgen receptor, impedes movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation) and inhibits binding to DNA. In preclinical experiments published in Science in April 2009(3), the novel, triple-acting, oral androgen receptor antagonist MDV3100 provided more complete suppression of the androgen receptor pathway than bicalutamide (casodex), the most commonly used anti-androgen drug. For further information, see the February 15th, 2011 issue of  ZERO HOUR – an action advisory from ZERO – the project to end prostate cancer.

Positive Phase III clinical trial results for MDV 3100 have been recently disclosed. See the November 18th, 2011 blog from this website.