Breast, Ovarian Cancer Drug Delays Progression in Advanced Prostate Cancer Patients with Specific Mutations.bjgabrielsen : August 20, 2019 8:01 pm : 2019, Treatment Information
Men with metastatic hormone-resistant prostate cancer (mCRPC) given Lynparza® (olaparib), a breast and ovarian cancer treatment, lived a clinically meaningful longer time without disease progression or death compared to those given standard treatment with Xtandi® (enzalutamide) or Zytiga® (abiraterone) in a Phase 3 trial. These eligible patients had a mutation in one of 15 DNA repair genes involved in the homologous recombination (HR) pathway. Specifically, these positive benefits were seen in patients with mutations in BRCA1, BRCA2, or ATM, the most common among HR gene mutations; the first two are also strongly linked with familial breast and ovarian cancers. Overall, HR mutations occur in approximately 25% of men diagnosed with mCRPC.
The multicenter, open-label PROfound study (NCT02987543) compared the efficacy and safety of Lynparza® to that of Xtandi® (from Astellas and Pfizer Oncology) and Zytiga® (from Janssen) in mCRPC patients whose disease had progressed while on these newer hormone treatments.
Lynparza®, an oral PARP (poly ADP-ribose polymerase) enzyme inhibitor marketed by AstraZeneca and Merck, is intended to prevent cancer cells from repairing their DNA errors, thereby causing their death. It is approved for some breast and ovarian cancers.
Patients in PROfound were treated with 300 mg twice daily of Lynparza®, or investigators’ choice of Xtandi® (160 mg daily) or Zytiga® (1,000 mg daily, plus prednisone). Lynparza’s safety and tolerability results were generally consistent with previous trials. The PROfound trial is expected to fully conclude in February 2021.
“This is the only positive Phase 3 trial of any PARP inhibitor in metastatic hormone-resistant prostate cancer, where the need for new, effective therapies is high,” according to José Baselga, AstraZeneca’s executive vice president, Oncology R&D. “The PROfound trial also demonstrates the potential value of genomic testing in this at-risk patient population.” Roy Baynes, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said trial results “represent the potential for a new, oral, and targeted treatment option for this patient population.”
Lynparza® is being tested in other prostate cancer trials, including the international PROpel Phase 3 study testing the addition of Lynparza® to Zytiga® as a first-line treatment of mCRPC patients who have not been given chemotherapy or newer hormonal agents (NCT03732820). PROpel is currently enrolling up to 720 men at sites across the U.S., Canada, Europe and elsewhere.
The material above was summarized from an article appearing in Prostate Cancer News Today, August 12, 2019 to which an e mail subscription is highly recommended.
Additional note on how PARP inhibitors work. DNA is damaged thousands of times during each cell multiplication cycle, and that damage must be repaired, including in normal as well as in cancer cells (which multiply and grow faster than normal cells). Otherwise, if DNA damage is not repaired, cells may die due to this damage. BRCA1, BRCA2 and PALB2 are proteins in cells that are important for the repair of double-strand DNA breaks by the error-free homologous recombinational repair, or HRR, pathway. PARP1 is a protein that is important for repairing single-strand breaks (‘nicks’ in the DNA). Drugs that inhibit PARP1 cause multiple double strand DNA breaks to form in this way, and in tumors with BRCA1, BRCA2 or PALB2 mutations, these double strand breaks cannot be efficiently repaired, leading to the death of the cells. Normal cells that don’t replicate their DNA as often as cancer cells, and that lack any mutated BRCA1 or BRCA2 still have homologous repair system operating, which allows them to survive the inhibition of PARP by drugs like Lynparza®.
In a Phase 2/3 OSPREY clinical trial aimed at examining its diagnostic accuracy, 18F-DCFPyl (PyL), a new imaging agent for positron emission topography (PET) scans, can accurately detect prostate cancer lesions outside the prostate, whether in nearby lymph nodes or in distant locations, clinical trial data show. The tracer — developed by Progenics — is a second generation fluorine 18-labeled small molecule that targets the prostate-specific membrane antigen (PSMA) protein, present at high levels in prostate cancer cells. Once bound to cancer cells, the radioactive fluorine serves as a signal for PET scans, making it possible to obtain an image showing the location of these cells.
Results from a Phase 2/3 trial examining PyL’s safety and accuracy were recently presented orally at the 2019 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting in Anaheim, California.
The completed OSPREY Phase 2/3 trial included 385 men either with high-risk prostate cancer who had been referred for radical treatment — surgical removal of the prostate and lymph nodes — and assigned to group A, or those who had radiological evidence of recurrent or metastatic cancer and were eligible for biopsy (group B).
To determine the safety and accuracy of PyL, these men underwent PET scans a couple of hours after the imaging agent was released into their bloodstream. Imaging results were then compared to specimens obtained during surgery for group A and biopsies from group B. Three independent readers examined the PET scans.
In group A, the scans led to very few false positives, but a sizable proportion of lesions identified as negatives were actually false negatives. (False positives indicate the presence of cancer at locations it’s not, and false negatives detect no cancer in locations where it exists.) In group B, imaging scans were much more accurate, with very few false negatives identified. This high specificity was seen across regions, both in pelvic lymph nodes and in more distant sites.
“[These results] underscore the power of PyL to accurately detect prostate cancer, including high risk and biochemically recurrent disease where more precise imaging can change treatment decisions,” Asha Das, MD, chief medical officer of Progenics, said in a press release. PyL was well-tolerated, with no serious adverse events related to the agent. Most frequent side effects were altered or unpleasant taste sensations and headache. “With our PSMA-targeted approach, we have the potential to detect small nodal and distant metastases, even in men with low PSA scores. We believe that PyL could transform how prostate cancer is detected, monitored, and treated,” Das said.
PyL is now being assessed in the open-label CONDOR Phase 3 study (NCT03739684) in about 200 men suspected of prostate cancer recurrence, who have had negative or equivocal findings on conventional imaging. The trial is currently recruiting at sites across the U.S. and in Quebec. Sites in the U.S. can be found in California, Connecticut, Florida (Moffitt Cancer Center), Iowa, Maryland (Johns Hopkins), Michigan, Missouri, New York, Pennsylvania, and Wisconsin.
The article above was first published in Prostate Cancer News Today, July 25th, 2019.
Among men suspected of having prostate cancer recurrence after surgery, the radiotracer 68Ga-PSMA-11 is better at detecting the cancerous lesions and provides better agreement among experts than the standard Axumin (18F-fluciclovine) tracer, a Phase 2 trial shows.
The results were presented at the 2019 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, held June 22–25 in Anaheim, California. The communication was titled “68Ga-PSMA-11 PET/CT detects prostate cancer at early biochemical recurrence with superior detection rate and reader agreement when compared to 18F-Fluciclovine PET/CT in a prospective head-to-head comparative phase 3 study.”
Radical prostatectomy — surgery to remove the prostate and surrounding tissues — is among the most common treatment options for prostate cancer. However, up to 40% of patients see their PSA levels increase after surgery. This process, called biochemical recurrence, indicates the return of cancer.
Doctors use various imaging methods to estimate the size and location of recurrent tumors before starting treatment. However, traditional techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and bone scans often fail to detect small tumors, especially at the early stages of biochemical recurrence, when PSA levels are low.
Positron emission tomography/computed tomography (PET/CT) is a highly sensitive imaging method that uses radiotracers — molecules that target specific cellular components, linked to small amounts of radioactive materials — and a special camera and computer to evaluate the function of different tissues. Researchers have developed radiotracers that specifically label components of prostate cancer, thus allowing its detection at earlier stages.
Axumin, by Blue Heart Diagnostics, is a radiotracer indicated to identify suspected sites of prostate cancer recurrence. It is a synthetic amino acid that preferentially enters prostate cancer cells due to their increased amino acid transport, labeling them with the radioisotope fluorine-18.
On the other hand, the 68Ga-PSMA-11 tracer consists of a molecule that binds the prostate specific membrane antigen (PSMA) labeled with the radioactive element gallium, Ga. This radiotracer can detect prostate cancer safely and accurately, but has not been compared with standard Axumin in clinical trials.
The Phase 2 trial (NCT03515577) compared the efficacy of PET/CT using either 68Ga-PSMA-11 or Axumin at detecting prostate cancer in 50 men with early biochemical recurrence, whose PSA levels ranged between 0.2 and 2 ng/mL.
Participants underwent Axumin PET/CT within two weeks before or after 68Ga-PSMA-11 PET/CT, and results were assessed by three independent imaging experts.
The study’s main goal was to compare the detection rates by patient and region. Secondary measures included detection rates according to initial PSA levels, the accuracy of each method, and agreement among readers.
Researchers found that the 68Ga-PSMA-11 tracer helped the experts identify prostate cancer lesions in significantly more patients (56%) than Axumin (23%). The PSMA tracer also identified more lesions by region — 30% versus 8% in the pelvic area, and 16% versus 0% in the extra-pelvic area.
Finally, readers agreed more on the results of this tracer, both by patient and by region.
“In patients with biochemical recurrence and low serum PSA levels after radical prostatectomy, PSMA PET/CT has higher detection rates and better reader agreement than Axumin,” researchers concluded. “Therefore, PSMA PET/CT should be the imaging modality of choice in patients with early biochemical recurrence.”
Published on line on July 8th, 2019 in Prostate Cancer News Today.
This website is normally directed toward men with prostate and other medical issues. But I found this blog and the succeeding one to be very applicable to many other life’s problems.
Isaiah 41:10 cites one of the clearest and most powerful promises God makes to those who have put their trust in Him as His servants. God says “Fear not, for I am with you; Be not dismayed, for I am your God. I will strengthen you, yes I will help you, I will uphold you with My righteous right hand.”
When one of God’s people is seeking an anchor in turbulent times (e.g. medical issues), this is the right passage for the job. Here, Isaiah writes about the source of a Christian’s strength. In verse 10, the Lord promises strength, help and protection. Moreover, He gives two commands; “Do not fear” and “Do not anxiously look about you.” Even as Christians, our enemy Satan as well as our own minds, can induce subtle and successful traps through the art of distraction. The evil one knows that fear can choke faith. In fact, fear and faith cannot occupy the same space simultaneously. He works hard through our mind to make unsettling circumstances a person’s sole focus. Once a believer’s attention is diverted from God, natural human tendencies take over. In the absence of prayer and worship, anxiety and doubt grow unobstructed.
Staying focused on the Lord can be hard. Our flesh prefers to seek security by thinking through all possible angles. Our tendency is to weigh what we think could happen against what “experts” say will happen, and then to evaluate possible ways of preventing our worst fears from coming true. Instead of becoming more confident, we begin to realize how powerless we are. Thankfully, we serve an almighty God who says, “Surely I will help you” (v.10). We can count on Him and agree with the Apostle Paul, “for when I am weak, then I am strong.” (2 Corinthians 12:10.)
By focusing on our circumstances, we’re actually choosing to feel anxiety and doubt. But these emotions don’t belong in a believer’s daily life. Instead, let’s decide to trust in the promises God has given us. He’s filled His Word with scriptural anchors (see Scriptual Medicines) to keep His children steady in the faith. To be continued in Part Two, “How to Have Two-Fold Peace.”
(A portion of the above was adapted from the “In Touch” Devotional by Dr. Charles Stanley, May 29th, 2019.)
God’s promises e.g. Isaiah 41:10, apply to us who have a personal relationship with Him through faith in Jesus Christ. Within the Christian experience, there is a two-fold sense of peace. We are promised the peace of God when we commit our troubles and requests to Him, peace that will guard our heart and mind as we abide in Christ. “Be anxious for nothing, but in everything by prayer and supplication (request), with thanksgiving, let your requests be made known to God; and, the peace of God, which surpasses all understanding, will guard your hearts and minds through Christ Jesus.” (Philippians 4:6-7).
But we can only experience the peace of God because we have peace with God. “Having been justified by faith” (declared or made righteous in the sight of God,) “we have peace with God through our Lord Jesus Christ.” (Romans 5:1). Both types of peace are important, but there is an order: first, peace with God; then the peace of God. Both are gifts of God’s grace, worthy of praise and thanks to Him.
If you are seeking God’s peace in your life, make sure you have peace with God first. Both are ours through faith in Christ. When we lack the peace of God, we should turn to our peace with God.
The above was published May 29th, 2019 in the devotional “Turning Point” by Dr. David Jeremiah.
The treatment landscape for metastatic prostate cancer is shifting and expanding yet again, according to new findings from two large clinical trials presented at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO). The ENZAMET trial tested the drug enzalutamide (Xtandi) and the TITAN trial tested apalutamide (Erleada) in men whose cancer is still responsive to hormone-suppressing therapies—also called castration-sensitive prostate cancer. In both trials, combining the respective drugs with the androgen deprivation therapy (ADT) substantially improved how long men lived overall and how long they lived without their cancer getting worse.
The ENZAMET trial enrolled more than 1,100 men with hormone-sensitive metastatic prostate cancer. The men were randomly assigned to ADT combined with enzalutamide or with any of three other androgen-blocking drugs. At a median follow-up of nearly 3 years, men who received ADT plus enzaluatamide had a 33% reduced risk of death, with 80% still alive compared with 72% of men treated with ADT plus another antiandrogen drug. Men in the enzalutamide group also had better clinical progression-free survival (PFS), which the research team defined as the time until the return of disease-related symptoms, the detection of new metastases on imaging scans or the initiation of another cancer treatment for prostate cancer, whichever came first. At 3 years, 63% of men in the enzalutamide group were alive without clinical progression of their disease, compared with 33% in the standard treatment group. Although enzalutamide appeared to be effective regardless of whether men had high- or low-volume disease, one apparent differentiating factor was planned early treatment with docetaxel (taxotere). Nearly half of the men in both treatment groups received early treatment with docetaxel and, for those men, enzalutamide was not associated with longer overall survival.
From the standpoint of efficacy, similar results were seen in the TITAN trial with apalutamide (Erleada). Funded by the drug’s manufacturer, Janssen Pharmaceuticals, the trial enrolled more than 1,000 men with hormone-sensitive, metastatic prostate cancer, with participants randomly assigned to receive ADT along with a placebo or ADT plus apalutamide. At 2 years of follow-up, approximately 82% of men who received ADT plus apalutamide were still alive compared with 74% in men treated with ADT plus placebo, for a 33% reduction in the risk of death. The trial’s other primary measure was the amount time men lived without evidence on imaging scans that their disease had progressed, known as radiographic PFS. At a median follow-up of nearly 2 years, men treated with ADT plus apalutamide had a 50% improvement in radiographic PFS than men treated with ADT alone.
What factors would influence the choice of treatments? In the case of enzalutamide and apalutamide, Dr. William Dahut, clinical director of the National Cancer Institute’s Center for Cancer Research said, both drugs “may be particularly good choices for men with low-volume disease, who might shy away from docetaxel” due to concerns about side effects. Unlike docetaxel, which must be administered intravenously in the hospital, enzalutamide, apalutamide, and abiraterone are oral drugs that can be taken at home, so they also offer greater convenience for patients. On the other hand, many patients tolerate docetaxel quite well, Dr. Dahut noted, and it’s given for a fixed duration, not continuously like the other drugs. Other factors such as insurance costs may also affect treatment choice.
For additional details, see the following article published June 19th, 2019 on line by the National Cancer Institute (NCI) Cancer Currents Blog.
Here is the 2019 guide from the Prostate Cancer Foundation.
Section One deals with General Information and Medical Basics. Section Two provides valuable information for those who are newly diagnosed. Section Three describes treatment options for localized or locally advanced prostate cancer. Section Four discusses aspects of living with and after prostate cancer. This guide is a valuable resource for any man with any interest in prostate cancer. Please circulate it.
Earlier this year, a series of informative videos dealing with several prostate cancer topics were produced by the Prostate Cancer Research Institute (PCRI). These included:\
1. The Best Prostate Cancer Diet by Dr. Mark Moyad;
2. HDR Brachytherapy (temporary seeds) for Intermediate Risk by Dr. Mark Scholz:
3. How Immune Therapy Works to Treat Prosate Cancer by Dr. Eugene Kwon;
4. Intensity-Modulated Radiation Therapy (IMRT) by Dr. Mark Scholz: and,
5. Impact of Lifestyle and Exercise on Prostate Cancer by Dr. Mark Moyad.
For more information, one can subscribe to the PCRI YouTube Channel for weekly videos. See the following link.
Study Suggests Enzalutamide (Xtandi) Better and Cheaper Than Abiraterone (Zytiga) for Metastatic, Hormone-Resistant Prostate Cancer.bjgabrielsen : May 29, 2019 12:49 am : 2019, Treatment Information
A recent study presented on May 3-6 at the American Urological Association’s 2019 Meeting found that treating metastatic, hormone-resistant prostate cancer (mCRPC) patients (who had not received chemotherapy) with Xtandi (enzalutamide) leads to better survival outcomes and lower healthcare costs than Zytiga (abiraterone acetate).
While therapies that lower male sex hormones (testosterone) — required for prostate cancer to survive and grow — are a mainstay of therapy for advanced prostate cancer, most patients will eventually acquire resistance to such approaches. This often happens because the cellular receptor for these hormones, called the androgen receptor, becomes constantly active, even in the absence of androgens. Therapies that inhibit the androgen receptor — such as Pfizer and Astellas’ and Xtandi and Janssen’s Zytiga — have largely improved the overall survival of prostate cancer patients, and are now approved for mCRPC patients in the U.S. and Europe. However, which treatment brings the most benefits or the lowest healthcare costs has not been addressed.
In this study, researchers performed a retrospective study to compare the overall survival and healthcare costs associated with these two second-generation androgen receptor inhibitors. They examined data from 3,174 adult men with mCRPC who had not received chemotherapy for at least one year before starting treatment with either Xtandi or Zytiga. Patients had been treated between April 2014 and March 2017, and their data were recovered from the Veterans Health Administration (VHA) database. Overall, 1,945 patients, mean age 73, received Zytiga, while Xtandi was administered to the remaining 1,229 patients, mean age 74.
After examining outcomes of these patients, researchers found that those on Xtandi lived for a median of 30 months, compared to 26 months for Zytiga. This represented a significant 17% reduction in mortality risk with Xtandi. Xtandi-treated patients also required fewer outpatient visits — both overall and cancer-related — than those treated with Zytiga, indicating that Xtandi led to a reduced use of medical resources. In line with this, Xtandi patients had fewer healthcare costs than Zytiga patients. In total, a patient treated with Xtandi would have a monthly healthcare cost of $8,085, compared to $9,092 for Zytiga. Prostate cancer-related costs were also lower for Xtandi — $6,321 versus $7,280.
Thus, researchers concluded that “chemotherapy-naive mCRPC patients treated with Xtandi had better survival, significantly lower resource use and healthcare costs than patients treated with Zytiga.”
The above appeared in the e mail Prostate Cancer News Today, May 16th, 2019.
I have not made such a request before on this website, however a situation has arisen with a good friend. Jim (not his real name) is a 60 years old man with advanced prostate cancer. He has received a number of customary treatment options none of which have curtailed the cancer. He is currently seeking to enroll in a clinical trial of a treatment regimen described earlier on this website. Please pray that if this treatment could be of help to Jim, that he would be accepted into the trial. Please pray for wisdom for his excellent physicians, and that God would extend Jim’s life, provide good quality of life and that God would be glorified in Jim’s treatment and disease. Jim shares his Christian faith openly with other men. Pray also for his family and the support they provide so well.
I was raised by wonderful Christian parents who took me to church regularly. I learned about God, Jesus, and well-known Biblical characters such as Noah, Moses, David, Jonah etc. This served as a good moral foundation but at one point, I realized that I knew about God and Jesus intellectually but did not know Him personally. That all changed when I realized that no matter how much of a “nice person” I could be, my good actions would never be enough to match God’s standard of perfect justice and holiness. It was then that I put my entire faith and trust in the fact that God’s Son, Jesus, had lived a perfect life and then given His life as a sufficient payment to God for all my sins and those of the entire world. At that point in time, I asked Jesus to come into my life, and thereby a personal relationship with God began. My life has never been the same since that day. As an “added bonus”, I was given the extraordinary gift of eternal life according to the famous verse John 3:16. “For God so loved the world, that He gave His only begotten Son (Jesus), that whoever believes in Him, should not perish but have eternal life.”
As the years have passed, I have come to realize that when I yield various aspects of my life to the loving and perfect will of a personal God and His glory, His best plans for me are a result though they might not always be the plans I had intended. For example, God has blessed my career, given me a wonderful wife, and even a fulfilling retirement. His presence has also been manifested in my health, even though I was diagnosed with early stage prostate cancer in 1995 and now am classified as having advanced prostate cancer though asymptomatic. The major lesson I have learned is that if I yield control of any area of my life to a personal and loving Heavenly Father, His best outcomes in accordance to His will are a result. They may not always be what I would personally choose, and many times life can be difficult, but God’s overwhelming peace and direction transcends every situation. In the words of the Old Testament prophet Jeremiah 29:11-12, “‘ 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. Then you will call upon Me and come and pray to Me, and I will listen to you.”‘
As a cancer patient, areas of my life to which I must daily present and yield control to God are my body, my mind and my overall health. To do that, I have found it very useful to pray the words written by the apostle Paul in the Bible in Romans 12:1-2 and insert my own name in the appropriate text as follows. “I urge you therefore, ——– (insert ones name), by the mercies of God, that you (I) present your (my) body as a living sacrifice, holy and acceptable, which is my reasonable service of worship. And do not be conformed to this world, but be transformed by the renewing of your (my) mind, that you (I) may prove (demonstrate) what the will of God is, that which is good and acceptable and perfect.” While this is not a guarantee of total earthly healing of my disease, who best to control my body than the One who created it in all its masterful complexity. While my cancer has not been healed, I can see God’s protective hand in my disease all these years through His power and often manifested by the excellent medical support which I have received. The ultimate healing will come when I will spend eternity in a new heaven and a new earth with a new body. Meanwhile, as Paul admonishes, I “press on.”
So if you have a personal relationship with God and are dealing with medical issues, I would sincerely suggest that you pray Romans 12:1-2 daily, yielding the direction and outcomes to the Lord. If you are not sure of your relationship with God, see the following link.
I am grateful for all of you who subscribe to receive my blogs by email the day after they are posted. However, it has come to my attention that on occasion the Godandprostate blogs end up in spam instead of my inbox. It has happened to me on a few occasions. Therefore, please check your spam folders occasionally to see if this has occurred. Thank you for your continued support.
Radioactive Lutetium-177 Compound Shows Promise As Therapy For Metastatic, Hormone-Resistant Prostate Cancer.bjgabrielsen : May 10, 2019 4:16 pm : 2019, Treatment Information
Treatment with the radioactive molecule lutetium-177-PSMA-617 (LuPSMA), which binds to the prostate-specific membrane antigen, is a potential therapeutic strategy for patients with metastatic castration (hormone)-resistant prostate cancer (CRPC), results from a Phase II pilot study suggest.
Prostate-specific membrane antigen (PSMA) is found at high levels in prostate cancers, particularly in patients with hormone-resistant disease — a form of cancer that no longer responds to hormone therapy and continues to progress. More research is assessing the potential of using agents that target this protein to deliver radioactive compounds directly into cancer cells. The LuPSMA molecule is composed of an anti-PSMA antibody bound to the radioactive compound Lutetium-177. Its safety and efficacy are being assessed in a pilot Phase 1/2 study by researchers at the Peter MacCallum Cancer Centre, Melbourne, Australia.
The trial enrolled 50 metastatic CRPC patients whose tumors were positive for the PSMA factor. Their cancer had progressed after standard treatments, including hormone therapy and chemotherapy, and they were offered four doses of LuPSMA, each given six weeks apart. Participants had rapidly progressing disease, taking 2.6 months to double their PSA levels — a marker of prostate cancer. Most patients had received the chemotherapies docetaxel (Taxotere; 84%) and cabazitaxel (Jevtana; 48%). Hormone therapy with Zytiga (abiraterone), Xtandi (enzalutamide) or a combination of both had been given to 90% of patients.
The study’s primary goals were to measure the number of patients whose PSA levels dropped and the treatment’s toxicity. Additional objectives included imaging responses, time patients lived without disease worsening, overall survival, and quality of life scores.
Investigators reported a reduction in PSA levels by at least 50% in 64% of patients, including 44% who experienced a reduction of at least 80%. Among the 27 patients with measurable disease at the study’s start, 56% experienced a partial or complete tumor reduction. The median time patients lived without disease worsening — measured through a rise in PSA levels — was 6.9 months. Their median overall survival was 13.3 months. A total of 14 patients received additional LuPSMA doses after their disease progressed. In nine of these patients (64%), PSA levels reduced by at least 50%. The most common side effects were dry mouth, nausea, and fatigue. Serious side effects were rare and included abnormally low levels of platelets and anemia, both detected in 10% of cases.
Overall, these early findings confirm the “high response rates and low toxicity with LuPSMA in men who had progressed after standard therapies,” even “in patients who subsequently progressed and were administered further LuPSMA,” the researchers wrote. “These results have provided the basis for randomised controlled trials currently underway,”
These findings were shared in a poster presented at the 2019 Genitourinary Cancers Symposium, Feb. 14–16 in San Francisco.
Darolutamide Delays the Spread of Prostate Cancer in Men with Non-Metastatic, Hormone-Resistant Disease.bjgabrielsen : April 25, 2019 8:38 pm : 2019, Treatment Information
Results from a Phase 3 clinical trial reveal that adding the androgen receptor inhibitor darolutamide to androgen deprivation (hormone) therapy (ADT) extends by 22 months the time men with hormone-resistant prostate cancer live without metastasis and without increasing the incidence of adverse events. The treatment also extended survival, time to pain progression, time until chemotherapy was needed, and kept patients alive and progression-free for longer periods than ADT alone, researchers reported.
The investigational drug darolutamide can help delay the spread of prostate cancer to other parts of the body in men with non-metastatic, hormone-resistant disease, according to results from the ARAMIS clinical trial. In addition, trial results showed that the drug appears to lack some of the side effects seen with similar drugs used to treat men with this form of prostate cancer.
Until recently, there had been no effective treatment options for patients with non-metastatic, hormone-resistant prostate cancer. These men have prostate tumors that continue to grow even after receiving androgen deprivation (hormone) therapy (ADT) to keep androgen (testosterone) levels in the body extremely low or undetectable. But over the last 2 years, two drugs have been approved by the Food and Drug Administration (FDA) to treat this form of the disease and some researchers expect that, based on the results of this new trial, darolutamide may be next.
The darolutamide findings, from an interim analysis of the ARAMIS clinical trial, were published in the New England Journal of Medicine and presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco on February 14.
The drug has a very favorable safety profile. The incidence of side effects was generally similar between the darolutamide group and the placebo group, noted study coauthor Karim Fizazi, M.D., Ph.D., of the Gustave Roussy Institute, University of Paris, who presented the results in San Francisco. Darolutamide was not associated with a higher incidence of side effects such as seizures, falls, fractures, cognitive changes, or hypertension. The ARAMIS climical trial results “strongly support the use of darolutamide” in patients with non-metastatic, hormone-resistant prostate cancer, said William Dahut, M.D., head of the Prostate Cancer Clinical Research Section of the National Cancer Institute’s (NCI) Center for Cancer Research.
Darolutamide, jointly developed by Bayer and Orion, belongs to a class of oral drugs called androgen (testosterone) receptor inhibitors. It prevents the binding of testosterone to the androgen receptor on a cell, thus blocking signals that prostate cancer cells require to grow and proliferate. In the body, these agents compete with androgens for binding to the androgen receptor, which reduces the ability of androgens to promote the growth of prostate cancer cells.
In 2018, the Food and Drug Administration (FDA) approved both apalutamide (Erleada) and enzalutamide (Xtandi) for men with non-metastatic, hormone-resistant prostate cancer. In the clinical trials that led to these approvals, the drugs were shown to improve the median time from random assignment until the tumor spread or the patient died—known as metastasis-free survival—in men with this form of prostate cancer. Treatment with both drugs, however, was associated with side effects related to the central nervous system, including fatigue, falls, and cognitive changes. In both trials, treatment with the respective drugs more than doubled metastasis-free survival compared with men who received a placebo: 40 versus 16 months in the apalutamide trial and 36.6 versus 14.7 months in the enzaluatmide trial.
The ARAMIS trial, which was sponsored by Bayer and Orion Corporation—the co-developers of darolutamide—included men whose prostate-specific antigen (PSA) levels were rising at a rate that has been associated with an increased risk of metastasis and death in previous studies. Metastasis-free survival was the primary endpoint of the trial; secondary endpoints included overall survival and the amount of time until a patient’s pain worsened.
The randomized trial included more than 1,509 men with non-metastatic, hormone-resistant prostate cancer whose PSA levels were rapidly rising while receiving hormone therapy. These men were considered to be at increased risk of having the disease spread to other parts of the body. All participants received ADT plus either darolutamide or a placebo. At a median follow-up of 17.9 months, the median metastasis-free survival was 40.4 months for patients receiving darolutamide plus ADT, compared with 18.4 months for patients receiving placebo plus ADT. The risk of metastasis or death from any cause was reduced by 59%. While more than half of patients were alive at the time of the analysis, the interim analysis pointed toward a 29% reduction in the risk of death for patients taking darolutamide. Also, the treatment extended the time patients lived without disease progression — 36.8 months versus 14.8 months — representing a 62% reduction in the risk of disease worsening or death. The 3-year overall survival rates were 83% in the darolutamide group and 73% in the placebo group, the researchers found. The median overall survival has not yet been reached in the study. The median amount of time until a patient’s pain got worse was longer in the darolutamide group than in the placebo group (40.3 months versus 25.4 months). It lowered the risk of needing a chemotherapeutic medication by 57%. The time to first skeletal event — such as radiation therapy to the bone, bone fractures, spinal cord compression, or bone surgery — was also longer with darolutamide.
Darolutamide has a different chemical structure than apalutamide and enzalutamide whose structures as similar, which the study authors believe may explain why it has fewer side effects. Darolutamide basically does not penetrate the blood-brain barrier, whereas apalutamide and enzalutamide do. The low incidence of central nervous system-related side effects seen in the trial was consistent with its rodent studies. Side effects likely to be related to the drug reaching the central nervous system include fatigue, dizziness, cognitive impairment, and seizures, according to the researchers. There was no detectable difference in the incidence of these side effects between patients treated with darolutamide and those who received a placebo, he added, noting that patients with a history of seizures were not excluded from the trial. In the trial, fatigue was the only side effect that occurred in more than 10% of participants in either group. A low incidence of side effects is particularly important for men who do not have symptoms of the disease, researchers noted. The percentage of participants who stopped taking either the drug or the placebo because of side effects was similar, i.e. about 9%.
In the coming years, researchers and patients hope to learn more about patient preferences for darolutamide, enzalutamide, and apalutamide. For example, an ongoing clinical trial is comparing two of these androgen receptor inhibitors, darolutamide and enzalutamide in men with metastatic hormone-resistant prostate cancer to determine which drug patients prefer based on their responses to a questionnaire. Patients will first take one drug and then the other. In the meantime, darolutamide has already received Fast Track designation by the U.S. Food and Drug Administration for the treatment of non-metastatic, hormone-resistant prostate cancer patients.
The information above appeared in the National Cancer Institute (NCI) e mail periodical, NCI@updates.cancer.gov, dated March 15th, 2019.
I recently received an e mail from the Cancer Treatment Centers of America (CTCA) entitled Health, Hope and Inspiration. These periodic e mails contain 30 minute interviews with Rev. Percy McCray, spiritual coordinator for CTCA. The latest interview entitled “Can God Use Cancer?” grabbed my attention. Rev. McCray’s immediate answer to the question was a resounding “yes”. During the interview, he cited a resource from CTCA entitled Cancer Ministry Scriptures, a compilation of Biblical references focused on leadership and inspiration, comfort, hope, God’s compassion, healing and strength, peace, and encouragement. This resource is similar to the section of this Godandprostate website entitled “Spiritual Medicines” to which I refer often. I was inspired to compile the latter after being told first-hand of God’s healing of a woman I knew from a brain tumor. Her son had compiled a short list of scripture verses which his mother cited and prayed daily in addition to taking her prescribed medicines. Her healing was confirmed by her surgeon at Johns Hopkins in Maryland.
During the interview with Rev. McCray, he focused on Philippians 1:12 wherein the apostle Paul cites a list of negative circumstances such as imprisonments, beatings, shipwrecks etc. but which all eventually had positive outcomes, namely that God used these events to further the propagation of His divine plan. Paul writes “now I want you to know brethren, that my circumstances have turned out for the greater progress of the gospel.” The things that happened to the apostle Paul and to ourselves can serve as a furtherance of God’s plan for us both personally and impersonally to those with whom we come into contact. Thus, God can use a cancer diagnosis for positive results. When one receives the initial diagnosis of cancer, there is often an emotional shock. But soon, we can realize that God did not give us the cancer but He has empowered us to accomplish something positive with this diagnosis. Cancer can open doors to share what God has done in our lives and the abundant life we have in Him through faith in Jesus. In John 10:10, Jesus proclaims that He comes to give us an abundant life. But a translation of the word “abundant” means an ability to rise above our circumstances. Had we never received a cancer diagnosis, we may have never considered it a ministry. God can show us elements of ourselves or ministry to others thru cancer. We are led to seriously consider the main bedrock purposes of our life. God can show us our strengths and especially our weaknesses thus enabling us to see that He Himself is the source of all our needs. We can see ourselves as little children who, when hurt, run to a loving parent for comfort. But now we see that God is that loving Father when we run to Him in faith and need. God’s promises in Scripture become alive as never before.
So what are the changes in my life and attitudes toward myself and others around me that have occurred as a result of a cancer diagnosis? Do we now focus more on actions that may have eternal results or consequences? These are questions we should prayerfully consider. For me personally, this website would never had been written had God cured me of prostate cancer during my initial surgery in 1995. But His care continues to permeate my life as it can any of us who have a personal relationship with God through Jesus Christ as described in the following link. In conclusion, may we be able to say with certainty that “we know that God causes all things to work together for good to those who love God, to those who are called according to His purpose.” (Romans 8:28).
In Psalm 55:16-17, King David says “As for me, I shall call upon God, and the Lord will save me. Evening, morning and at noon, I will complain and murmur, and He will hear my voice.” God’s ears are open to our cries and His shoulders are wide enough to carry our burdens. He is sovereign over the universe, so He is certainly capable of working out our problems and meeting our needs. I recently read an exercise that helped make casting my cares on Him a practical act.
First, take a piece of paper and write down the things that cause your anxiety. For me, as a 77- year old prostate cancer patient, my first item was that my cancer continue to be controlled, and that I not die of this disease. Upon further thought, there were other items that were cheating me out of peace but I will focus on the cancer here.
Next, pray each issue into God’s care. For me, praying the words of Romans 12:1, and inserting my own name as follows, is a daily act. “I urge you therefore” ____(your name), “by the mercies of God, to present your (my) body, a living and holy sacrifice, acceptable to God, which is my spiritual” (some versions say rational) “service of worship.”
Finally, as you pray, visualize placing the situation into God’s omnipotent hands. Imagine handing our bodies over to the Lord, while saying, “Father, I give you my disease or condition. You are more than sufficient to handle it, and I trust You to guide me.”
Some people may resist this suggestion because certain pseudo-spiritual movements have a method they call visualizing. But above, the term refers to the beautiful word pictures throughout the Bible, which God intended to help us understand our relationship to Him. This type of visualizing creates a mental snapshot of God doing just what He says He’ll do in Psalm 55:22, “cast your burden upon the Lord and He will sustain you. He will never allow the righteous to be shaken.” He also says “do not be anxious for your life as to what you shall eat, or what you shall drink, nor for your body.” (Matthew 6:25).
When you have transferred all your worries to God’s hands, wad up the paper and then destroy it. In doing so, you symbolize the transaction that just took place. Your cares are no longer yours – every one of them belongs to the Lord. Then walk away in perfect peace.
If you are not sure whether you have such a personal relationship with God, see the following.
Much of the post above, was published in the January 5th, 2019 In Touch devotional, written by Dr. Charles Stanley.
This post is a bit out of the ordinary but I first want to thank all of you who read this website. As many of you know, anyone can subscribe to automatically receive the blogs by e mail as they are posted by entering an e mail address on the right side of the home page. The posts cover a wide variety of prostate issues including general patient information, screening, diagnostics, genetics, imaging, and treatment at various stages. Also included are posts dealing with encouragememt from a Christian perspective which I have found useful during my own disease journey. I want to ask you faithful readers to send this blog to any men in your community who could possibly benefit from reading this site and tell them they can subscribe. Word-of-mouth is the best way to disseminate the information to as many men as possible. They can sign up and read only those posts that apply to their individual interests. Thank you in advance for doing this.
Meanwhile, I want to share the funniest story I know dealing with urological issues. A 90-year old man goes to his urologist for a checkup. Physically, he passes with flying colors. During the exam, his urologist asks, “how are you mentally?” “Oh”, the man exclaims, “I am as sharp as a tack for my age. I remember names, dates, and hardly ever misplace anything.” “Amazing”, proclaims the urologist, “and how are you spiritually?” “I am glad you asked”, the man confidently responds. “God and I are like that”, he said crossing his fingers. “We are tight. In fact, I’ll give you an example. At night, when I get up to go to the bathroom, a surreal glow guides my path. Upon finishing and returning to bed, the surreal glow dissipates”. The urologist listens intently, shakes his head in amazement and at the end of the visit, he tells the man how extremely fortunate he is for his age. Several weeks go by and the urologist accidently runs into the man’s wife at a local supermarket. He greets her and says, “congratulations on your husband. Physically he is fine, he is mentally sharp and spiritually, he related to me a most unusual phenomenon. He says that when he gets up at night to use the bathroom a surreal glow guides him and when finished to return to bed, the surreal glow dissipates.” Upon hearing this, his wife’s face droops, eyes widen, mouth opens, as she exclaims, “oh my goodness, he’s peeing in the refrigerator again.”
According to Dr. William Oh, Deputy Director of the Tisch Cancer Institute, Chief of the Division of Hematology and Medical Oncology, and Professor of Medicine at the Icahn School of Medicine at Mount Sinai in New York, there are six myths about chemotherapy.
Some prostate cancer patients shy away from or choose not to utilize chemotherapy. Their hesitation may result from an outdated understanding of chemotherapy’s side effects and its effectiveness against prostate cancer. In this blog, Dr. Oh explores the myths driven by common misperceptions about chemotherapy and replaces them with some facts.
MYTH #1: Chemotherapy is a last resort.
“Some patients believe that we use chemotherapy when we are out of options. Far from a last resort, there are currently promising studies utilizing chemotherapy earlier in the treatment of prostate cancer. For instance, in men with newly diagnosed metastatic disease, chemotherapy significantly improves survival.”
MYTH #2: Chemotherapy is a single and outdated option.
“Chemotherapy is not a single drug. In fact there are many “chemotherapies”, both oral and intravenous, and new chemotherapies are being developed and approved regularly.
In prostate cancer, there have been continuous improvements over the past few years. In the past, an older drug called mitoxantrone was approved by the FDA to relieve cancer symptoms only. Then something important happened in 2004: docetaxel (taxotere) chemotherapy was shown to be the first drug to improve overall survival for men with metastatic prostate cancer that became resistant to hormone treatments. This was a critical milestone, as no drugs to that point could lengthen survival. In 2010, the FDA approved another chemotherapy drug for prostate cancer called cabazitaxel.
Far from being outdated, these advancements allow me as an oncologist to have a larger toolbox to treat cancers which adapt to different types of treatments. For instance, resistance often develops to drugs like abiraterone or enzalutamide, which target the androgen receptor. Chemotherapy may more effectively kill those resistant cancer cells.
Finally, ongoing research will determine how best to combine chemotherapy with other drugs and radiation as well as use biomarkers to personalize treatment. We thought chemo might go away with newer treatments, but we use it as often as we did before as men are living longer and better lives with advanced prostate cancer.”
MYTH #3: Chemotherapy has no role in an era of immunotherapy and precision medicine.
“Some people believe chemotherapy is a ‘shotgun’ approach. Patients want more targeted therapy specific to their cancer. The fact is we do have specific chemotherapy to kill prostate cancer cells called taxanes. Taxanes stop cancer cells from dividing and also may interfere with androgen receptor signaling in prostate cells as well.
In fact, when a patient stops responding to drugs such as abiraterone or enzalutamide, a blood test for a biomarker called ARV-7 predicts greater benefit from chemotherapy than to continue the androgen pathway drug. This test is now approved in the U.S.” (See a recent blog on this website describing AR-V7 testing.)
MYTH #4: I’ll be nauseated and vomiting throughout my chemotherapy.
“Chemotherapy induced nausea and vomiting (CINV) can be very scary and intimidating and many patients have known or heard about someone who has had it. Two things are really important to understand about CINV.
First, there are many types of chemotherapy and their ability to cause CINV varies widely. In fact the drugs used in prostate cancer are unlikely to cause this. The American Society of Clinical Oncology (ASCO) Guidelines consider cabazitaxel, for instance, as a ‘low risk’ drug for causing CINV.
Second, modern antiemetics have revolutionized the treatment of CINV. Antiemetics are drugs used to prevent nausea and vomiting and there are a host of agents available to use. Typically I will incorporate one of these on the day of therapy and prescribe something for home, but most patients do not need it.”
MYTH #5: I won’t be able to function day-to-day while on chemo.
“Some men believe their quality of life will drastically suffer while on chemotherapy. Fortunately, these newer drugs have much fewer side effects. The most common side effect in day-to-day life is fatigue. This is usually mild to moderate and I find that most patients are able to continue many of their regular activities. For instance, they may continue to work, spend time with family, and exercise.”
MYTH #6: I’ll permanently lose all my hair after chemo.
“It is true that many prostate cancer patients experience temporary hair loss while undergoing chemotherapy. Some patients won’t lose their hair at all. Others will experience thinning hair.
In nearly all patients, the hair loss is reversible once chemotherapy is complete. If you experience hair loss, your hair should grow back several months following your chemotherapy treatment.”
FACT: Chemotherapy is a key treatment in the fight against advanced prostate cancer.
“Battling prostate cancer may be the hardest fight you’ve encountered. Certainly, the side effects of some of the treatments you’ve received have been difficult. There is no question that chemotherapy comes with its own set of challenges.
However, it is critical to understand how important chemotherapies used to combat prostate cancer can be in extending and even improving your life. Many studies have shown that drugs such as docetaxel, cabazitaxel, and others can play a key role in treating metastatic prostate cancer, cancer that has spread beyond the prostate.
Please ask your oncology team about any specific concerns you may have before starting any treatment regimen. Knowledge is the most effective tool in the battle against prostate cancer.”
See the following link from Zero-the Fight to End Prostate Cancer, published Jan. 10, 2019.