A western Norway fjord; Provided by Arnold Dalene.
I always knew the day had to come when the therapy I had been given for the last ten years inhibiting cancer cell growth would stop working and my PSA would start increasing despite the treatments. I had been living my life in four month increments of time between PSA tests. Now on December 5th, I finally saw the PSA rising uncontrolled. My local urologist called it “a bad day”, gave me a hug, kissed my wife on the cheek and in a “dismissal speech” said I’d have maybe 2-3 good years left before the painful and eventually fatal effects of advanced prostate cancer would manifest themselves. Meanwhile my oncologist told me I could maybe get ten years “if I hit the jackpot” in terms of additional therapies [e.g. enzalutamide (Xtandi® and abiraterone (Zytiga®] now available to me as an asymptomatic but metastatic patient. These drugs were not available as long I did not have clinical metastases. (I now see a medical need for the development of new therapeutic agents for prostate cancer patients like me who are asymptomatic yet metastatic.)
For several days, my mind was numb. I now could see an end-of-life coming into view. Even my personal relationship with God and Jesus seemed light years away through a combination of fear of dying, anger at therapeutic failure and extreme anxiety of near-future events. In my daily devotionals, I pleaded with God to allow me to hear something positive from Him now even though I knew He had spoken to my heart and mind many times in the past. An answer came from the Old Testament prophetic book of Micah 6:3-5 where God says to His people (and to me) “what have I done to you and how have I wearied you?” I quickly answered “You allowed the therapy that had worked for so long to fail.” Then He reminded me of so many instances in the past where He had delivered me from near-fatal accidents and illnesses just as He reminded His people (Israel) in verses 4-5 of the times He delivered them e.g. by parting the Red Sea among others. Then in verse 8, God reminded me to simply continue to “walk humbly with my God.” In addition, in the book of Hosea, God tells Israel (and me) “what shall I do with you”, your faith is like dew on morning grass which evaporates as soon as the hot sun hits it. Also as Jesus told His disciples when the storm arose nearly overwhelming them in their boat followed by His calming of the sea, “why are you so anxious, have you so little faith?”
While in this state of despair, I came upon a clinical trial of a new PET/CT scan imaging agent under development at Johns Hopkins designed to identify and localize tiny pockets of metastatic cancer sites. Upon contacting them, I was informed overnight that I would be an ideal candidate for the scan which I eventually received on December 12th in Baltimore. While my physicians and I had hoped the scan would find nothing, or perhaps one metastatic site which could be treated, the scan revealed three very small sites of cancer in three different lymph nodes which did not lend themselves to remedial treatment. In my disappointment however, I remembered that 13 years earlier I had a CT scan (Prostascint) at Hopkins which revealed the same three sites and which had not grown on size over the thirteen years that I was under hormonal therapy. I and my physicians took some encouragement in this comparison. But now of course, that limitation of starving the cells and controlling their growth is lifted.
So where does this leave me and perhaps you the reader if you can relate to my condition? Medically, I am in a watch-and-wait-and re-scan mode with several potential treatments available including immunotherapies like Provenge and soon Prostavac if and when needed. I am grateful for a team of cutting-edge and communicative physicians at Johns Hopkins (Maryland) and Moffitt Cancer Center in Tampa. In addition, I was honored to be asked to give a talk along with my Hopkins urologist at a conference entitled “Medicine and Religion” in March, 2017. I intend to describe my personal spiritual and medical experiences including “lessons learned” as described on this website over the years.
I have been reminded over and over to remember what God has told me in the past predominantly through His Word, the Bible and so directly and unexpectedly several times. Jesus has said He would take care of my body as long as I continue the “mission” He has given me of allowing Him to be seen through my cancer. (See the April 30th, 2015 link).
God may also want to change me from the inside rather than my circumstances. When we wait in silence before God, it gives Him the opportunity to communicate His thoughts to us. In Psalm 62:1,5 David writes, “my soul waits in silence for God only; from Him is my salvation…..My soul, wait in silence for God only, for my hope is from Him.” Verses 11-12 state that “power and lovingkindness belong to God.” It may be His will that I keep my prostate cancer but God will deliver me now in this life as well as in my eternal life which I possess as a free gift through personal faith in Christ.
I am also learning how to combat the negative cloud of anxiety which seems to overwhelm me at times of bad news. In Romans 12:1-2 the apostle Paul writes, “I urge you….to present your bodies a living and holy sacrifice, acceptable to God, which is your spiritual service of worship; and do not be conformed to this world, but be transformed by the renewing of your mind, that you may prove what the will of God is, that which is good and acceptable and perfect.” How do I “renew my mind”? In Christ, I am to become a “living sacrifice”. I need to say to Him as my Savior and Lord, “I trust You. Whatever You want me to do I am willing.” Then He “transforms” me by renewing my mind to focus on things that please God and are in my best interest as well. God will never call on us to do something for which He has not already equipped us.
God has also told me (through my wife) that what He can accomplish in and through me is directly proportional to how much I depend upon Him.
And so the journey continues. More medical and spiritual posts to come. If you cannot relate to having a personal, communicative relationship with God through His Son, Jesus Christ, see this link.
Hans Edvard Wisloff was a prominent Norwegian Lutheran Bishop, theologian and writer in the mid 20th century. Being of direct Norwegian ancestry myself, I found this short essay of encouragement.
“God has given us permission to bring everything to Him in prayer. Nothing is too big, nothing too small. He has promised that He will hear us; He has asked us to come boldly. God says what we ask in faith as we pray, we shall receive.
Faith is confidence. Faith does not command. In confidence and trust it leaves all in God’s hand. Faith acknowledges that we are short-sighted and that we do not always know for what we should pray.” (It has been suggested that when we pray, we should first be silent and ask God to tell us what He wants us to pray for.) “Faith clings to the wisdom of God. It knows that God knows best what we need. Therefore, the prayer of faith contains the phrase ‘according to Your will.’ The prayer of faith leaves everything in the Father-hands of God and from that moment knows that it is God who has assumed responsibility in our case.”
There has been a lot written recently about positron emission tomography (PET) scans. The following is a link to an overview published in Medical News Today on December 16th.
The following was added today to this website section entitled “Lessons Learned”.
We know that God has specific plans for our lives and knows in advance what we have to experience, both positive and negative. God told Moses in advance that Moses was to specifically lead Israel out of bondage. Yet Moses loudly proclaimed his weaknesses to God basically saying, “I can’t do this, You need to find someone else.” But as we know, Moses’ and Israel’s circumstances did not change but God changed Moses by showing him a series of examples of God’s power. So while our own personal circumstances may not change, God may use other people, methods, events and especially His Word to change us, “perfecting” us for any task we need to accomplish according to His will.
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.