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).
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.
DNA sequencing of a person’s tumor can be very important in determining treatment plans among other potential applications. The National Cancer Institute (NCI) today published an excellent review of methods used to obtain a person’s genetic information and how this information could be applied. It is written in a way that can be clearly understood by non-medical personnel. See the following link.
Patients with low-to-intermediate prostate cancer who receive low-dose permanent brachytherapy, a type of radiation therapy, have excellent outcomes in the long run, according to data recently presented at the American Society for Radiation Oncology (ASTRO) 2017 Annual Conference. At nine years of follow-up, only a minority — 11-14 percent — of patients treated with either iodine-125 (I-125) or cesium-131 (Cs-131) brachytherapy had seen their cancer return, as assessed by a rise in PSA levels.
Brachytherapy is a relatively new cancer treatment that implants small radioactive seeds directly into a patient’s tumor. This ensures that radiation is delivered specifically to a cancer site while sparing healthy surrounding tissues. The seeds used in brachytherapy may be composed of diverse radioactive compounds. Cesium-131 seeds, in particular, have unique attributes that are seen to shorten treatment time and reduce common prostate side effects.
Results published in The International Journal of Radiation Oncology, Biology and Physics in August 2017 showed that patients treated with cesium-131 seeds have shorter recuperation periods, recovering their urinary, bowel, and sexual functions quicker than with other brachytherapy solutions. Iodine-125 seeds are also being used. Results found that the relapse-free survival rate was similar in both groups: 89% in the I-125 arm and 86% in the Cs-131 arm.
Together with the prior data, the findings support the use of low-dose permanent brachytherapy as a viable therapeutic option for localized and lower-risk prostate cancer patients.
As described in recent website blogs, utilizing one’s immune system to combat cancer (immunotherapy) is at the cutting edge of prostate cancer research and cancer research in general. I am personally familiar with an on-going National Cancer Institute (NCI) clinical trial combining the prostate cancer vaccine Prostvac and the checkpoint inhibitor antibody Opdivo® (nivolumab), currently approved by the FDA for the treatment of non-small cell lung cancer. On October 12th, it was reported that the National Institutes of Health (NIH), the nation’s medical research agency announced a partnership with eleven leading biopharmaceutical companies to accelerate the development of new cancer immunotherapy strategies. This Partnership for Accelerating Cancer Therapies (PACT), a five-year public-private research collaboration totaling $215 million is part of the Cancer Moonshot. PACT will initially focus on efforts to identify, develop and validate robust biomarkers — standardized biological markers of disease and treatment response — to advance new immunotherapy treatments that harness the immune system to attack cancer.
NIH, the nation’s medical research agency, includes 27 Institutes and Centers of which the National Cancer Institute (NCI) is the largest. NIH is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.
New immunotherapies have resulted in dramatic responses in certain cancer cases. They have also been the focus of intense investment by biopharmaceutical companies seeking to provide new options for patients who do not respond to other cancer therapies, but they don’t work for all patients. Development and standardization of biomarkers to understand how immunotherapies work in some patients, and predict their response to treatment, are urgently needed for these therapies to provide benefit to the maximum number of people.
The biopharmaceutical companies are expected to contribute $55 million over the five years while NIH will contribute $160 million. For more information and for the companies involved, see the following link. For more information about NIH and its programs, visit www.nih.gov
For the many years I have been treated for prostate cancer, I have been blessed by God with a wonderful, caring, praying and compassionate wife. I am sure this has helped my current asymptomatic status and hopefully my prognosis. This theme was amplified today when I read the following article published October 9th in MedlinePlus, a health-based news service from the U.S. National Library of Medicine of the National Institutes of Health. The article describes the clinical benefits of a happy marriage as they relate to cardiovascular disease; however I see no reason why it couldn’t be extrapolated to prostate and other cancers. I suggest you read the linked article.
Men ages 55-69 who don’t get PSA (prostate-specific antigen) screening tests for prostate cancer may want to reconsider that choice based on an April 2017 recommendation from the United States Preventive Services Task Force (USPSTF), a government advisory medical panel who evaluate the benefits and harms of health services. A few years ago, this same panel discouraged many men from having the PSA test.
As most of you know, the PSA test measures a protein level that rises both in men with prostate cancer and other prostate disorders. The test has several shortcomings including the risk of a false-positive result. Only about one in four men with an elevated PSA level who undergoes a prostate biopsy actually has prostate cancer according to the National Cancer Institute. However, a biopsy can have serious side effects such as bleeding, infection and pain. Up to half of prostate tumors identified by the PSA test and confirmed by a subsequent biopsy are harmless and will never cause symptoms or death. Yet many men proceed to treatment with surgery or radiation for low-risk cancers even though treatments can cause long-term side effects such as incontinence and erectile dysfunction.
In 2008, the USPSTF advised men 75 and older to pass on PSA screenings concluding that the potential harms outweighed the benefits of cancer detetction. In 2012, the panel extended the recommendation to include all men saying in essence “do not screen” resulting in a serious decline in PSA screening. Meanwhile the number of men over 75 diagnosed with prostate cancer that has metastasized rose from 7.8% to 12% according to the Journal of the American Medical Association Oncology. Authors of the study suggested that the decline in PSA screening led to the rising number of men being diagnosed with advanced prostate cancer.
The USPSTF has now reversed its course to some extent encouraging men ages 55 to 69 with average risk to discuss PSA testing with their doctors and share the responsibility for deciding whether or not to be screened for prostate cancer. The group still discourages testing for men younger than 55 or older than 69. Other groups such as the American Urological Association advise men with a family history of prostate cancer or African-American ancestry to begin screening (including a digital rectal exam) before age 55. It is also reasonable for select healthy men in their early 70’s to request screening too since they may live an additional 15-plus years.
It is suggested you ask your doctor if you should be screened and why. For more information on prostate symptoms, see the Sept. 25th post. If you decide to be screened, discuss how often you should be tested; every other year makes sense for many men while annual testing may be preferable for those with risk factors.
Risk factors include age, race and family history. As you get older, the risk of developing prostate cancer increases dramatically. The average age at diagnosis is between 65 and 70 years. Black men are at highest risk whereas rates for white men and hispanics are 40-50% lower. Asian, Pacific Islander and American Indian men have the lowest rates. You have double the risk if you have a first-degree relative (father or brother) with prostate cancer. Second-degree relatives (uncle or grandfather) with prostate cancer confer only a small risk increase.
(Much of this material was taken from the Sept. 2017 issue of the University of California Berkeley School of Public Health Newsletter.)
