From Dismay to Hope: Advanced Prostate Cancer, PROVENGE and Prolonging Life.

Christmas for me has always been a joyous occasion but this past December, 2016 it included an element I had always dreaded. My prostate cancer had been kept under control with a combination of intermittent and continuous Lupron® injections for ten (10) years. Every time I had received positive results from my PSA tests, I felt as if God had given me a 4-month reprieve of life.  I could forget my cancer for a while and live my life happily and productively until the next test. I knew I wouldn’t be cured but I had hoped above all hopes that the hormone therapy would work long enough for me to die of another, less-painful scenario. In December 2016, I found that the hormone treatments had stopped working and I was now classified with refractory, advanced prostate cancer though thankfully asymptomatic. My Florida urologist had always hoped that this “bad day” would never come but now he told me I could expect 2-3 “good years” of alternative treatments until metastatic disease would overtake me. He shook my hand and referred me to the care of my Florida oncologist. Upon seeing my oncologist, his first words to me were “what do you want to do now?” Though I am a Ph.D. scientist, I am neither an M.D. nor a trained oncologist so I looked at him with a sense of bewilderment and confusion. I later learned that this approach was something called “patient-centered care” wherein I was to be totally involved in my therapy. Information shared below indicates that my first choice of therapy, PROVENGE® (sipuleucel-T), way be the right one.

Well, in writing this website I knew something about the few therapeutic agents available to me at this stage, so my oncologist and I listed them including enzalutamide (Xtandi®), taxotere (docetaxel®), abiraterone (Zytiga®) and PROVENGE® (sipuleucel-T). In looking over my website listing of drugs currently under development for advanced prostate cancer, I was dismayed to note the significiant number of late clinical stage failures [e.g. custirsen (OGX-011),  galeterone (TOK-011), orteronel (TAK-700), ipilimumab (Yervoy)] which reinforced the fact that my options were getting fewer and the prospect of dying of prostate cancer was becoming more of a reality. Since I am asymptomatic at this point, another possibility was to do nothing until symptoms or metastases appeared on various scans. I remembered that I had written a blog dated October 28th, 2014 wherein four prostate cancer experts had recommended the early use of PROVENGE® in treating refractory, asymptomatic disease. Fortunately, PROVENGE® was available for me at my specific treatment site and in April, 2017 I started my treatment which I will describe below.

PROVENGE was studied in Phase 3 clinical trials involving 512 men with metastatic, hormone-resistant prostate cancer in the IMPACT trial. It was found that PROVENGE had a more pronounced treatment effect in men with lower, decreasing baseline PSA. Thus, men with lower cancer burden may benefit most from PROVENGE therapy administered at an early stage of advanced cancer. These men may tend to experience less immunosuppression systemically and in the tumor microenvironment. Immuno-treatment such as PROVENGE also has a delayed onset of action and is capable of generating a sustained response. Therefore treatment earlier in the disease would allow more time for the patient to benefit from the therapy. This data seemed to fit my current status. My oncologist refers to me as “the best of the worst”.

As published in the June 2013 issue of Urology [Schellhamer et al; 81(6),1297-1302] the median overall survival in men whose baseline PSA was lower than 22 ng/mL was 41.3 months as opposed to 28.3 months in the control, untreated group for an overall median survival benefit of 13 months. Estimated 3-year survival for the lowest PSA group receiving PROVENGE was 62.6% for PROVENGE patients versus 41.6% for the control group.

Was God leading me in this choice? Clinical trial data for PROVENGE seems to indicate it is an excellent choice for me at this point. I have a sense of peace especially as God has paved the way for me in the administration of this therapy even to the point of giving me good, useful veins as would be needed (see below). Is it possible that God could extend one’s life even though His Word states that He has our days “numbered?” One day, my daily devotionals included a section from the Old Testament book of Deuteronomy, often not known for its inspirational themes but a more historical book. In this reading, Deuteronomy 6:2 seemed to leap out at me. It states that I should “fear (respect) the Lord your (my) God, to keep all His statutes and commandments…….all the days of your (my) life, and that your (my) days may be prolonged.” Did God intend to speak to me through this verse? Could He prolong my days? I cannot say for certain. But even though I don’t know how many years I have left, I daily “present my body a living and holy sacrifice acceptable to God which is my spiritual service of worship” according to Romans 12:1. I will trust in God’s wisdom and that of my physicians. I’ll keep writing this website. As I believe Jesus once told me (see video link), I’ll keep doing what He told me to do and He’ll care for my body.

How Provenge works: PROVENGE is a cellular immunotherapy designed to induce an immune response targeted against prostatic acid phosphatase (PAP), an enzyme (antigen) produced (expressed) by prostate cells and found in higher amounts in most prostate cancers. PROVENGE consists of a patient’s own white blood cells [T-cells, B-cells, natural killer (NK) and other cells] including antigen-presenting cells (APC), specialized white blood cells that help fight off foreign substances that enter the body. These APC cells send out signals to T-cells (other immune system cells) when an antigen enters the body. In PROVENGE, a person’s APC’s have been activated with a synthetic combination (recombinant) of two human proteins, PAP and granulocyte-macrophage colony stimulating factor (GM-CSF) an immune cell activator. These activated immune cells may be able to recognize and attack certain prostate cancer cells. During the process of generating PROVENGE from a person’s white cells, the resulting mixture remains active outside the body for only a matter of days. Therefore it is imperative that the patient and physicians adhere to a personalized leukapheresis and infusion schedule usually three days apart.

Approximately three days before receiving Provenge®, white blood cells (T-cells, B-cells, etc) are collected by passing whole blood extracted through a small tube (catheter, a large bore needle) placed in a vein in the right arm through a machine which extracts the white cells and the unextracted blood is returned through a smaller needle placed in a vein in the left arm. This process called leukapheresis usually takes about three hours. If the arm veins are insufficient for the blood collection, then a venous catheter will be placed into a vein in the next or upper chest. I was told at the blood bank that a catheter is necessitated in the majority of cases but even though some medical personnel have difficulty drawing my blood, my arm veins were of sufficient quality to be used (a real praise). The collected cells are then sent to a laboratory where PROVENGE is generated.  The prepared sipuleucel-T (PROVENGE) solution (which has an expiration time) is then shipped to a local infusion center, where it is injected back within three (3) days after collection. The infusion takes about an hour. The entire collection, cell transformation and re-injection process is very time-dependent and requires strict coordination between blood-drawing centers, laboratory and infusion sites. While there are some side effects possible, I only experienced mild fatigue after the collection and infusion processes. The process is somewhat cumbersome yet very do-able and worthwhile if prescribed for your early stage advanced cancer.

Updated PSA Screening Guidelines Now Stress Patient Choice

When three different prostate cancer websites post the same subject article, it is significant. According to the April 11th MedLinePlus from the U.S. National Library of Medicine, in a significant shift, a key health advisory panel plans to soften its recommendation against prostate-specific antigen (PSA) screening for detecting prostate cancer. In 2012, the U.S. Preventive Services Task Force recommended that men no longer get their PSA tested. That recommendation was based on evidence that PSA screening resulted in overdiagnosis and unnecessary treatment that could leave men impotent and incontinent. Now, after reviewing follow-up evidence, the task force is recommending that men aged 55 to 69 have a discussion with their doctor about the pros and cons of PSA screening. For men aged 70 and older, the recommendation for no PSA screening remains in place.

The recommendation states PSA-based screening provides a small benefit for men ages 55 to 69, and that physicians should inform this group about the potential benefits and harms of PSA-based screening for prostate cancer. In addition, the statement pointed out that the decision of whether to screen or not should lie with the individual man, after an informed discussion with his physician.

The task force is an independent, volunteer panel of experts in prevention and evidence-based medicine that makes recommendations about preventive medical services, such as screenings, counseling services, and preventive medications.

“There is probably a small benefit overall to screening,” said task force chair Dr. Kirsten Bibbins-Domingo. She is a chair in medicine and a professor of medicine, epidemiology and biostatistics at the University of California, San Francisco. “But the right decision is not a one-size-fits-all decision. The right decision isn’t screening all men, it’s making all men aware of the benefits and harms, and then allowing each man to make the best decision for himself,” Bibbins-Domingo explained. The recommendation applies to men who have not been diagnosed with prostate cancer and have no signs or symptoms of the disease, Bibbins-Domingo said. In addition, the recommendation is for men at average risk and those at increased risk for prostate cancer, such as black men and men with a family history of prostate cancer. Men at increased risk for prostate cancer should take that into consideration when making the decision to be screened for PSA levels, she said.

One specialist, Dr. Anthony D’Amico a professor of radiation oncology at Harvard Medical School. views the new recommendation as a correction of an error the task force made in 2012. The more you follow the studies that look at the benefits of PSA screening, the more positive they are becoming, he said. Because prostate cancer takes many years to develop, the benefit only becomes apparent 10 to 20 years after the start of a study, he explained. Based on longer follow-up of studies, “the task force is backing off from, ‘Do not screen,’ to ‘Let’s talk about it,’ and then, I would say, in time, it will probably come to, ‘We think you should do it,'” he said.

This important news was also published in the April 13th Prostate Cancer News Today as well as the April 18th Zero-The End of Prostate Cancer Newsletter.

 

 

 

 

My Presentation With Dr. Jacek Mostwin (Johns Hopkins) at the 5th Conference on Religion and Medicine, March 25th, 2017, Houston, Texas

A few months ago, my long-time Johns Hopkins urology surgeon, Dr. Jacek Mostwin, suggested that we prepare a joint presentation for the meeting cited above. I readily agreed. The annual conference on Religion and Medicine encourages physicians, care-givers and hospital pastoral staff to see their patients as more than data, results and medical information but instead as unique, multi-faceted, spiritual  individuals. The effects of spirituality on medical conditions and outcomes is a general theme.  The conference is a way to support the religious experience that is often left behind by more secular bioethics in modern medicine. This meeting has also created a growing community of many different types of people who are interested in the human side of medicine. This interfaith forum and growing community includes practitioners who feel the religious dimension of their work is important, and theologians and chaplains who may feel otherwise quite marginalized in secular medical centers – here they find a sympathetic medical collegiality.

The text of our 15-minute talk is as follows.

God and Prostate.net; Illness, Mortality, Faith, Evangelism and the Doctor-Patient Relationship in the Digital Age

Introduction as presented by Dr. Jacek Mostwin, Johns Hopkins. “I am here today with my friend and colleague, Dr. Bjarne Gabrielsen, to talk about his website, Godandprostate.net, and its intertwining, related themes: Illness, Mortality, Faith, Evangelism and the Doctor-Patient Relationship in the Digital Age. In 1995, Dr. Gabrielsen became my surgical patient for treatment of prostate cancer. It quickly became clear that we shared a belief in the role of faith in medical experience. We have remained in close contact over these 22 years. For Dr. Gabrielsen, faith is the heart of life. The website Godandprostate.net is a public extension of his spiritual diary; a personal blog integrating medical and spiritual entries. It is a bold testament of belief in God’s faithfulness and an affirmation that life’s many stages have meaning.”

My presentation. “My name is Bjarne Gabrielsen. I have a Ph.D. in organic chemistry with research interests in medicinal organic chemistry and natural products. My career was spent equally in academia (University of Florida) and government, the last 20 years at the National Cancer Institute (NIH) where I retired as a Senior Advisor in Drug Discovery and Development. I am first generation Norwegian-American, raised in a conservative Lutheran background, and married for the first time in 2000 at the age of 58 (very happily). I am also a prostate cancer survivor since 1995 now classified as having advanced prostate cancer though asymptomatic (thank God). Through the years, I have been blessed with first-class medical support.

My personal story starts in 1995 when I received the dreaded phone call from Johns Hopkins that my biopsy had revealed prostate cancer. It didn’t take long for God to intervene and make His presence known. Sharing the news with a close friend later that morning, I noticed a sparrow walking unafraid at my feet. Immediately, the word came to me from Luke 12:6-7, “Are not five sparrows sold for two pennies? Yet not one of them is forgotten by God. Don’t be afraid; you are worth more than many sparrows.” Shortly thereafter, God gave me Dr. Mostwin who performed successful surgery at Hopkins in late 1995. The night of my surgery, I was reading my Bible when Dr. Mostwin visited me. We had a brief but meaningful conversation about how one can believe and trust the words written in the Bible. Looking back on this incident, the theme of the truth and relevance of God’s Word would dominate my future years. My cancer, though treated at a very early stage, recurred biochemically in 2002, which devastated me at the time. Additional radiation therapy did not eradicate it completely. Looking back now, I see that God allowed this in my life so I could create my website among other reasons. God always has a long-range purpose for us even in what we perceive at the moment to be devastating developments.

I had started a personal spiritual diary in 1995 expanding it from 2002-2010. During these years, Dr. Mostwin asked me to examine a book written by a prostate cancer survivor to comment on its value for others. I read it and concluded the author provided limited encouragement even though he had been anointed with oil by his church leaders as described in James 5:14-15, and performed in many Christian denominations. Such anointing with oil would play a huge role in my own life in 2004. Dr. Mostwin then seriously suggested I write my own book. I decided on a website instead since books have endings and websites go on. Godandprostate.net now comprises over 250 separate posts and has over 820,000 hits. There are medical posts from journals and periodicals and spiritual ones from various devotional books in a 2:1 ratio. A Medical Resources section includes information from the National Cancer Institute, Prostate Cancer Foundation, Prostate Cancer Research Institute, Johns Hopkins etc.  Medical topics are updated regularly such as; finding the right physicians, resources for newly diagnosed men, prostate cancer for beginners, scans and imaging, pathology, approved treatments and side effects, immunotherapies, clinical trials, life style, diet, nutraceuticals and vitamins like D3. Spiritual sections include: a) “Scriptural Medicines” (Biblical verses and promises of encouragement); b) “God Still Heals Cancer” (two personally known examples of healing from brain and breast tumors); c) “How to Enter a Personal Relationship with God” (a general and personal testimony) and lastly, d) “Lessons Learned” (or being learned on a personal level).

Can there be a major purpose of disease? Isaiah 40:1 says “comfort, comfort my people says your God.” Isaiah’s mission was to comfort the hurting people of Israel. Likewise today there are countless hurting people who need God’s comfort. Illness of any kind can be a training ground to prepare us to share comfort with another. I may be asked to endure the same afflictions that are plaguing others before I can truly be of comfort and help.

Now I will present nine lessons learned or being learned:

1) God has a specific goal for all aspects of our lives. Jeremiah 29:11-12 states “for I know the plans that I have for you declares the Lord, plans for welfare and not for calamity, to give you a future and a hope.” But can those God-ordained plans include prostate cancer? Our abstract states that “diseases of one kind or another and eventual death are things we will all experience. We all want every aspect of our lives to have significance, be of value to others, be meaningful and fulfilling including our education, career, family, friends, specific interests and talents. But what about sickness, disease and eventual death? Can these fit the “meaningful” category? My answer is “yes”, hence my website written to empower and encourage men. Many people desire that a higher power be involved in many aspects of their lives. Why shouldn’t God be involved in diseases and eventual death? We don’t cease to exist if a disease such as prostate cancer takes our lives. God has a purpose for everything even prostate cancer. Jesus and His disciples once encountered a man who had been blind from birth. His disciples asked Jesus why the man had been born blind to which Jesus answered that “it was in order that the works of God might be displayed in him” (John 9:3). And so it can be with prostate cancer. God’s ideal plan consists of two main goals; a) to glorify Himself and His Son Jesus through all aspects of our lives including sickness and disease; and, b) to experience that “God causes all things to work together for good to those who love God.” (Romans 8:28). God uses sicknesses to glorify Himself, to increase our faith, to allow others to see God and Jesus in us, and, to make us more sensitive to people around us and their specific conditions.

2) God speaks to us about our conditions predominantly from His Word, the Bible. God may speak through prayer, circumstances, our experiences or interactions with others but these are always coupled with a specific scriptural promise or reference. We can even question God about our conditions. But we should reject the tendency to focus on our circumstances, negative emotions and fears, but instead trust on God’s promises in His Word. His Word is filled with scriptural anchors (see scriptural medicines section) to keep us steady in the faith.

3) We have the assurance that through our relationship with God through faith in Jesus, we will live forever, in a new heaven and a new earth with a new, perfect body. Life is a series of “anticipations.” When we were 12, we looked forward to being a teen, then graduating, then a successful career, then marriage and family, then retirement, but then what??? We should always have a goal to which we aspire and live each day intentionally. We all will eventually die of one cause or another. Having the assurance of eternal life in spite of potentially life-threatening conditions, totally changes our outlook. This assurance based on God’s Word (e.g. John 3:16) removes the fear of death (though we often fear the process of dying). It also gives true inner peace knowing that the best is yet to come in “the twinkling of an eye” when we are transported from this life to the next, immortal phase.

4) God’s purposes can often be to change us rather than our circumstances. While our own circumstances may not change, God may use other people, events and especially His Word to change us inwardly, “perfecting” us for any task we need to accomplish according to His will.

5) Focus on issues and relationships in our lives which would have the most lasting or eternal effects. I must accept that in my life, I can care for others as unique individuals and possibly affect them. Writing a personalized “legacy letter”, I can share the most important issues and experiences in my own life as they would relate to any one friend, colleague or family member, voicing specific thanks for past experiences and a hope for an eternal future together.

6) Remember the times God has previously protected and delivered us. In the Old Testament, God often instructed Israel to erect a monument at a specific site in remembrance of God’s previous miraculous deliverances. They were constantly reminded to “remember when God…..”. We likewise are instructed to celebrate God’s faithfulness and remember what God has done previously in our lives and how He has delivered us in the past. His faithfulness remains to this day and forever.

7) Learn to cope with life’s “thorns”.  Acknowledge our own weakness. Like the apostle Paul, many of us are given “thorns in the flesh”, namely conditions which we’d rather not have but which God has not chosen to remove. Mine has been prostate cancer. The apostle Paul had his “thorn” most likely a condition involving his eyesight. But through it all, God’s message is that “His grace is sufficient” and God’s “power is perfected in our (my) weakness.” Recognition of my helplessness unleashes God’s power. I need to affirm as the apostle Paul did, that when I am weak (in myself), then I am strong (in Christ). What God can accomplish through me and my life experiences is directly proportional to my level of dependence on Him.

8) Learn to experience the peace of God. Even though it is hard not to think about the fact that there are cancer cells in me, instead I should receive the gift of peace offered in John 14:27, “Peace I leave with you; my peace I give to you; not as the world gives do I give to you. Let not your heart be troubled nor let it be fearful.”

9) Lastly, be thankful for everything, taking nothing for granted. I have so much for which to be thankful including a wife whom I cherish, many supportive friends, a career that I could not have planned nor imagined for myself, and most of all, an eternal life in God’s presence in a new heaven and a new earth with a new body to which I can aspire. Finally I am very thankful for the opportunity you all have given me to share with you today.”

Concluding remarks from Dr. Mostwin. “When I was a surgical resident at the University of Michigan in Ann Arbor in the late 1970’s, surgical attendings would invite their patients to come before the entire department to speak about their experiences. A subliminal message conveyed to us was the unique bond between surgeon and patient that extended beyond the operating room and the hospital bedside, something that seemed special for me then, though I did not understand how and why. We don’t do that sort of thing very much in medical education now. But in this presentation, we have done just that and in doing so have shared with you the closeness of medicine, faith and the unique circumstance of life that brought us together and kept us that way. We are grateful for your attention.”

P.S. Only an hour or so before the presentation, Dr. Mostwin shared with me two very pertinent verses he had just read in his daily devotional as follows. “I have told the glad news of deliverance in the great congregation. I have not restrained my lips, as Thou knowest O Lord. I have not hid thy saving help within my heart. I have spoken of Thy faithfulness and Thy salvation; I have not concealed Thy steadfast love and Thy faithfulness from the great congregation.” (Psalm 40:9-10).

Yervoy Fails to Shut Down Prostate Cancer But Could Be Used in Combination Therapy

A recent article from Prostate Cancer News Today (April 4th) stated that Yervoy (ipilimumab) showed little benefit when administered to 16 patients awaiting surgery with locally advanced prostate cancer at the University of Texas M.D. Anderson Cancer Center. The study was published in Nature Medicine.

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 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. Specifically, it targets cytotoxic T-lymphocyte antigen-4 (CTLA-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. The bad news however is that prostate cancer responds to Yervoy by increasing the expression of two other immune checkpoint molecules, PD-L1 and VISTA. And both send a “don’t-eat-me signal” to immune cells. That reaction is why Yervoy, by itself, offers little patient benefit.

Yervoy increased the numbers of T-cells in tumors, as well as another kind of immune cell, macrophages. But researchers also discovered that the tumor cell tissue had two proteins on their surfaces, PD-L1 and VISTA, that were not there before treatment. These proteins are called immune checkpoints because they can stop the chain of events that lead to an immune reaction. Basically they signal the shutdown of T-cells in the tumor environment. These results are prime examples of the dynamic state of the immune system; when a change is made in one specific area, it may manifest itself in other areas simultaneously. It is like trying to alter one card while not changing other cards comprising a house of cards.

“Observing immune response at one point in time doesn’t reflect what’s going on because the immune system is so dynamic,” said Dr. Padmanee Sharma, a professor of genitourinary medical oncology and immunology at the University of Texas MD Anderson Cancer Center. You can change the immune response with Yervoy, but what else changes becomes incredibly important.

Compressing Eight Weeks of Radiation Into Four Weeks Is Just As Effective in Treating Localized Prostate Cancer

I received the following article by e mail from a recent issue of Prostate Cancer News Today. I am posting it however I urge the reader to discuss the findings cited herein with a radiation oncologist if it may apply to your treatment.

According to an article published in the April 1st, 2017 edition of the Journal of Clinical Oncology, four weeks of radiation therapy at larger doses has the same effect as conventional radiation therapy administered to prostate cancer patients over eight weeks, according to results from a Phase 3 randomized clinical trial of 1,206 men in Australia, Canada and France. The findings provide a new standard of care for men at intermediate risk of prostate cancer. The PROFIT Phase 3 trial (NCT00304759) followed participants for a median of six years.

“External beam radiation, a treatment option for localized prostate cancer, is commonly used alone for men with intermediate-risk disease. The treatment is typically delivered in 37 to 42 sessions, given five days a week over the course of 7.5 to 8.5 weeks. Studies have suggested that hypofractioned radiation therapy, given over a shorter time with larger doses per fraction, is also an option, but some experts raised concerns about increased toxicity and reduced tumor control. Even so, modern radiation therapy techniques are highly specific and can deliver hypofractioned radiation therapy without increased toxicity by avoiding radiosensitive normal tissues. Researchers hypothesized that hypofractioned radiation therapy given in 20 fractions over four weeks would be similar in efficacy — and without increased toxicity — to standard radiation therapy, delivered in 39 fractions over eight weeks.”

Co-principal investigator Charles Catton, a radiation oncologist at Toronto’s Princess Margaret Cancer Centre, stated that “using modern radiation therapy techniques that are very precise, we determined there was no noticeable difference between eight- and four-week treatment regimens in terms of cancer control or side effects of treatment. In fact, for some men, the shorter regimen meant slightly fewer side effects (particularly regarding bowel function) and therefore improved quality of life. The compressed course of treatment is of great benefit to patients and also to the system in terms of being able to treat more patients in less time.”