From Prostvac to Fear Then to Faith

Early 12th century Viking Christian chapel near Larvik, Norway; photo: Bjarne Gabrielsen

As many of you readers know, I have earlystage, asymptomatic but advanced prostate cancer. After treatment with Provenge, I was informed (perhaps divinely through a former colleague) of a National Cancer Institute (NCI) clinical trial currently recruiting patients like myself. The protocol involves treatment with the vaccine Prostvac and the antibody therapy, Opdivo. I had written about this in earlier posts. Since that time, Yervoy (ipilimumab) has been removed from the trial and most recently a large Phase 3 trial of Prostvac has been discontinued. Independently, I had been informed about the potential toxicity of Yervoy which reinforced my anticipation of the trial; but then the news of Prostvac’s lack of success seriously dampened my enthusiasm. It was just at that time when a devotional (August 13th) from Our Daily Bread Ministries placated my fears and inflated my faith that I was indeed pursuing the right track in my treatment.

The message was from an Old Testament prophet named Habakkuk who served as an inspiring example of  someone who argued with God yet came to the point of trusting Him regardless of the impending circumstances. Habakkuk states (Hab. 3:16-19), “I heard and my heart pounded, my lips quivered at the sound; decay crept into my bones and my legs trembled.” However in contrast, “though the fig tree does not bud and there are no grapes on the vines, though the olive crop fails and the fields produce no food, though there are no sheep in the pen and no cattle in the stalls, yet I will rejoice in the Lord, I will be joyful in God my Savior.”

What do we do when circumstances are beyond our control or when the outlook seems hopeless? The prophet Habakkuk’s situation was out of his control and the fear that he felt terrified him. The coming judgment could be catastrophic. Yet, in the midst of the impending chaos, Habakkuk made a choice to live by his faith and rejoice in God. He did not place his confidence and his faith in his circumstances, ability or resources but in the goodness and greatness of God. His trust in God compelled him to proclaim: “The Sovereign Lord is my strength; he makes my feet like the feet of a deer, he enables me to treat on the heights.”

When we are faced with difficult or unknown circumstances, we too have only to place our faith and trust in God to be our strength. He is with us in everything we face.

Are you unsure of whether or not you have a personal relationship with God? See the following.

Waiting for God’s Love and Compassion

Florida bobcat kitten looking for its mother; Photo: BJ Gabrielsen

For several weeks, I had been undergoing a cutting-edge, experimental cancer treatment. I firmly believed God had led me to this stage by a totally unexpected but logical pathway. My oncologist had also enthusiastically concurred with my choice. One of the few ways to determine therapeutic progress in this trial is by measuring one’s prostate specific antigen (PSA) level. Mine had not decreased at all but had steadily increased over the first weeks. I was becoming skeptical as to whether or not this experimental regimen was to offer any clinical benefit and even more seriously, I was beginning to doubt whether God had actually led me to this point.

Then one morning I happened to read a portion from the Old Testament book of Lamentations 3: verses 19-26 written by the prophet Jeremiah. Specifically the prophet was imploring God to “remember my affliction….and bitterness. Surely my soul remembers and is bowed down within me.” Clearly Jeremiah was depressed and worried. However, he remembers that “the Lord’s lovingkindnesses indeed never cease for His compassions never fail. They are new every morning; great is Thy faithfulness…. Therefore I have hope in Him. The Lord is good to those who wait for Him, to the person who seeks Him. It is good that he wait silently for the salvation of the Lord.”

The Bible encourages us to move toward faith and away from doubt. Actually, faith and doubt cannot co-exist in reality. But many of the Biblical giants we read about such as Abraham, his wife Sarah, Jacob, Moses, David, and numerous prophets of the Old Testament as well as Jesus’ own disciples doubted. But as a group, they all came directly to God with their doubts. Some of them argued and even hollered at God, but they didn’t walk away.

Waiting on the Lord is a kind of wrestling, taking our doubts and questions to Him because we know He is the only one who can help. No matter how hard the questions or the situation, “his mercies are new every morning (vv. 22-23) and His faithfulness is abundant. God’s love and compassion are always with us for He never abandons us. But in another sense, we often desire to see His love in action or to experience it first-hand in our personal circumstances.

This is the only reason we’re not crushed under life’s burdens and difficulties. The challenges to our faith are very real as evidenced by the scriptural use of the words “affliction, bitterness, wandering, and downcast” (depressed). Yet they are outweighed by God’s love and faithfulness as they are absolutely perfect. The most hopeful thing we can say is “the Lord is my portion” (translated ‘share’ or ‘inheritance’); “therefore I will wait for Him” (v. 24). This urges us to wait quietly and patiently without grumbling or complaining. The Lord sustains our very lives.

So personally I wait. I invoke the words of David in Psalm 37:7. I need to “rest” (or be still) “in the Lord and wait patiently” (longingly) “for Him”. To be continued; my treatments continue.

If you are uncertain of your own personal relationship with God, see the following website link.

A portion of the above was an excerpt from “Today in the Word”, a devotional published by the Moody Press, Chicago, IL.

Agent Orange and Prostate Cancer

I personally know of two Vietnam era veterans who were exposed to Agent Orange during their military service; both contracted prostate cancer. Hence it was of interest that I read the following linked article from the Prostate Cancer Foundation describing long over-due efforts to study and determine the best prostate cancer diagnostic (as to aggressiveness) and treatment options for such veterans.

Prostate Cancer Patient Guide Manual – Must Reading

HIGHLY RECOMMENDED: The Prostate Cancer Foundation (PCF) recently published (November 2017) an electronic patient guide which can be downloaded to your computer or obtained as a hard copy. Main topics include: 1) You and Prostate Cancer – General Information -Medical Basics; 2) For the Newly Diagnosed; 3) Treatment Options for Localized or Locally Advanced Prostate Cancer; 4) Living With and After Prostate Cancer; 5) What to Do if Your PSA Starts to Rise; 6) Cutting Edge Developments in Prostate Cancer Research; and, 7) For Our Sons and Daughters (genetics). One can receive the guide from the PCF electronically or by mail.

Enzalutamide (Xtandi) Delays Metastasis in Hormone-Resistant Prostate Cancer

Adding Xtandi® (enzalutamide) to hormone therapy reduces the risk of cancer spreading in patients with non-metastatic, hormone-resistant prostate cancer (CRPC), new Phase 3 trial data shows. Additional results were announced by Pfizer and Astellas Pharma, the drug developers. “Many prostate cancer patients who initiate hormone therapy will experience disease progression illustrated by a rising PSA level, and currently, there are no FDA-approved treatment options for patients with non-metastatic CRPC until they develop confirmed radiographic metastatic disease,” according to Dr. Neal Shore, MD, director, Carolina Urologic Research Center.

Pfizer and Astellas initiated the multinational PROSPER trial to determine the effects of Xtandi® in men with non-metastatic CRPC. The trial enrolled approximately 1,400 patients with prostate cancer that had progressed, based on rising PSA levels, despite androgen deprivation (hormone) therapy (ADT) but with no symptoms or other evidence of metastasis. Participants were randomly assigned Xtandi® plus hormone therapy or a placebo plus hormone therapy. The study’s primary endpoint was metastasis-free survival, which is the amount of time passed until the cancer spread.

Results seen in the PROSPER study showed that Xtandi® plus ADT delayed clinically detectable metastases compared to ADT alone in patients with non-metastatic CRPC whose only sign of underlying disease was a rapidly rising prostate-specific antigen (PSA) level.  Xtandi® is already established as a standard of care for men with metastatic CRPC based on the results of prior studies, such as AFFIRM and PREVAIL, which demonstrated that Xtandi® delayed disease progression and improved overall survival in men with clinically detectable metastatic disease. For additional information, see the following link.

It seems that Xtandi® (enzalutamide) and ARN-509 (apalutamide) share similar biological properties and mechanisms of action. Perhaps there differences in pharmacologic properties due to their differing chemical structures but they seem similar. (See the Nov. 10th post for comparison.)

Apalutamide (ARN-509), a Potential New Therapy for Non-Metastatic Hormone-Resistant Prostate Cancer.

Janssen-Biotech has submitted a new drug application to the Food and Drug Administration (FDA) for apalutamide (ARN-509) to treat non-metastatic hormone-resistant prostate cancer. Apalutamide is an oral androgen receptor inhibitor that blocks the action of testosterone in prostate cancer cells. (Whether ARN-509 differs in its mechanism of action from enzalutamide [Xtandi] is not known to this website at this point.)  The drug had been tested in the Phase 3 SPARTAN clinical trial in men with non-metastatic hormone-resistant cancer who have a rapidly rising prostate specific antigen (PSA), despite receiving continuous androgen deprivation (hormone) therapy (ADT). The primary objective of the trial was to assess metastasis-free survival, or the time from randomization to first evidence of confirmed metastasis (the spread of cancer cells to another part of the body). Janssen revealed that patients receiving ADT plus apalutamide lived significantly longer without metastasis, compared to those receiving ADT plus a placebo. But the company did not disclose any further details. The hope is to treat men with prostate cancer earlier in the disease course before the cancer has metastasized.

Studies have estimated that between 10 and 20 percent of patients diagnosed with prostate cancer might develop the hormone-resistant form within about five years. Moreover, metastatic hormone-resistant prostate cancer is associated with deterioration in quality of life and few therapeutic options. For details about the FDA approval process, see the following link.

Am I On the Right Track? Encouraging Good News on Nivolumab (Opdivo)

Ailments anyone? 1900-1930 pharmacy in Chokoloskee, FL (Everglades); Photo: BJ Gabrielsen

In December 2016, when I first embarked on my latest course of prostate cancer treatments, it seemed logical to me to treat the cancer first by stimulating my immune system; therefore, Provenge® (sipuleucel-T) was my first choice. That course of three treatments were administered quite readily. Immediately after receiving Provenge®, I was unexpectedly made aware (from a former NCI colleague as I may have written in an earlier blog), of the National Cancer Institute (NCI) clinical trial in which I am currently participating wherein I receive the vaccine Prostvac and the monoclonal antibody therapy nivolumab (Opdivo®). Nivolumab, an immune checkpoint inhibitor, is already approved for the treatment of several other cancers, including melanoma, bladder cancer, head and neck cancer, and Hodgkin’s lymphoma. Laboratory studies have shown that immune cells found within tumors often overexpress (over-produce) the protein PD-1 which is targeted by nivolumab, and which prevents those immune cells from recognizing and attacking the cancer cells. (For more information on how nivolumab works, see the May 15th, 2017 post.) So at this point, I am fully engaged in the NCI biweekly trial.

As a Christian, I continuously seek God’s plan for all aspects of my  life certainly including my now 22-year old battle with prostate cancer. God and Jesus (in that still small voice) have reinforced the message to me on several occasions that they are very much involved in my disease and treatment which I have previously described on this website. But I am human; doubt and lack of faith in God’s Word and His promises periodically creep in. I generally start each morning by spending twenty minutes or so reading Bible passages as cited in 2-3 daily devotional books. A few days ago, as I was quietly meditating and praying, I asked God “am I really on the right track here with this trial or am I just deluding myself? Is this really part of Your plan for me?” Many clinical trials don’t work out as positively as researchers had hoped they would. In many trials, only a small subset of patients experience positive results. I thought “could I be engaging in wishful-thinking, that this trial would be overall successful and that Prostvac and Opdivo® would retard my cancer specifically? After all, I had been involved in biomedical research at NCI for over fifteen years before retirement, therefore this trial has an excellent chance of success right? Is this really where you want me at this time, Lord?” From my heart, I asked God to show me if I am following the right therapeutic path or not.

After pleading my case to God and embarking on the day, I immediately checked my e mails and, there again was a totally unexpected article from the National Cancer Institute. The October 23rd NCI article stated that “on September 22, the Food and Drug Administration (FDA) granted accelerated approval to the immunotherapy drug nivolumab (Opdivo®) for some patients with advanced liver cancer (hepatocellular carcinoma).” This is in addition to the cancer types in which nivolumab had already produced some positive responses and in the current trial, it is being paired with a specific prostate cancer vaccine. The message I perceived was that God was telling me again to stay the course, “you are where I want you to be.” Do I believe I will be cured? Physicians say no, but God is certainly able to heal me if it is His will. Whatever the case, I will be content and fully trust in His overall game-plan. I have nowhere else to go for such divine wisdom, love and care. Periodically, as I have needed and asked for, God has given me these confirmatory signposts as I travel this journey. I believe this was another such marker. If you are not sure if you have a personal relationship with God in your life, see the following section. (To be continued).

Bad News and Then Good News Next.

For men with metastatic, hormone-resistant prostate cancer, treatment with Taxotere (docetaxel) and prednisone has been shown to  improve survival. But few treatment strategies are available if this first-line therapy fails. Second-line therapy of anti-cancer agent Jevtana with the steroid medicine prednisone is currently used, with favorable data reported in 2010. However, new options are still needed to improve patients’ survival.

In the international AFFINITY trial, researchers assessed whether adding custirsen to Jevtana after failure with first-line Taxotere would improve survival in the overall patient group and within subgroups with poor-prognosis. Recent results from the AFFINITY Phase 3 trial shows that combining custirsen (OGX-011) with Jevtana (cabazitaxel) and prednisone does not improve survival of metastatic hormone-resistant prostate cancer (PC) patients who progressed after prior Taxotere (docetaxel) treatment.

Custirsen inhibits the production of clusterin, a stress-induced glycoprotein (a protein with a carbohydrate attached to it) that prevents cell death. Levels of clusterin are increased in some forms of cancer, including prostate cancer. Importantly, clusterin has been associated with treatment resistance.

Therefore, in light of the results above, treatment with Jevtana and prednisone “remains the standard of care for patients with metastatic hormone-resistant prostate cancer progressing after Taxotere chemotherapy. For details see the following link.