Additional Studies of Opdivo (nivolumab) in Combination with Rubraca in Prostate Cancer and Other Applications of Opdivo.bjgabrielsen : September 13, 2017 2:25 am : 2017
Editorial note: I am writing some of this post while awaiting Hurricane Irma to pass my home directly in about 1-2 hours.
Opdivo® (nivolumab) and the prostate cancer vaccine Prostvac are being combined in a National Cancer Institute clinical trial described in posts on this website dated May 15th and August 7th, 2017. Bristol Myers Squibb and Clovis Technology will collaborate to assess the combination of Opdivo® (nivolumab) and the PARP inhibitor, Rubraca (rucaparib) in Phase 2 and 3 clinical studies in patients with different cancer types, including prostate cancer.
The companies plan to launch a Phase 2 study to investigate the safety and effectiveness of the combination treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). All studies are expected to begin before the end of 2017.
“We are very enthusiastic about studying Rubraca and Opdivo® in combination, and the potential to create new treatment options for patients with multiple tumor types, as well as for patients beyond those with BRCA mutations,” according to Patrick J. Mahaffy, Clovis Oncology’s president and CEO. “This substantial clinical collaboration in ovarian, triple-negative breast and prostate cancers represents a significant effort by Clovis and Bristol-Myers Squibb to realize that potential,” he said.
Cancer cells are constantly multiplying, but the division process is sometimes associated with errors that may cause their death, such as DNA breaks. If cancer cells repair these breaks, they survive and keep multiplying.
Rubraca is an oral inhibitor of PARP proteins (PARP-1, PARP-2, and PARP-3), which are involved in DNA repair. By inhibiting these proteins, Rubraca prevents cancer cells to repair their DNA. Indeed, previous studies have shown that PARP inhibition promotes inflammation, cell death, and increases the action of T-cells within tumors.
Opdivo® acts upon a protein called programmed cell death-1 (PD-1), which inhibits the immune system’s ability to detect cancer cells. By inhibiting PD-1, Opdivo® restores the body’s capacity to activate the anti-tumor response and fight cancer cells. Because of its potential role as an enhancer of the immune system’s response, Opdivo® is under evaluation in a broad range of clinical trials across all phases in a variety of tumor types. For more information, see the following.
Additional results involving Opdivo® include an article published September 11th in MedlinePlus describing research suggesting that Opdivo® — a drug that works with the immune system to fight melanoma — is more effective than the current standard of care for patients who’ve had surgery to remove advanced tumors. In addition, an August 17th post from the National Cancer Institute Current Contents stated that the Food and Drug Administration has approved Opdivo® for patients with metastatic colorectal cancer that has one of two specific genetic features and whose disease has progressed after chemotherapy.
The National Cancer Institute (NCI, the largest of the institutes of the National Institutes of Health, NIH) recently published an excellent fact sheet describing many aspects related to prostate-specific antigen (PSA) testing. Specific subjects addressed include: a) what is the PSA test? b) Is the PSA test recommended for prostate cancer screening? c) What is a normal PSA result? d) What if screening shows an elevated level? e) Limitations and potential harms of using the PSA test for prostate cancer screening; f) Recent research on prostate cancer screening; g) How is the PSA test used in men who have been treated for prostate cancer? h) What does a PSA increase mean for men who have been treated? i) How are researchers trying to improve the PSA test?
Decreasing bone mineral density (BMD) is also an undesirable side effect of androgen deprivation (hormonal) therapy (ADT). The therapy is associated with many potential adverse effects, including significant bone loss and increased risk for low trauma or fragility fractures similar to that in persons with primary osteoporosis. A recent review of clinical trial results revealed that patients with non-metastatic prostate cancer receiving ADT can benefit from osteoporosis therapies, known as bisphosphonates e.g. (Fosamax, Boniva), and from Prolia (denosumab), which significantly increase bone mineral density (BMD). The review, entitled “Bone Health and Bone-Targeted Therapies for Nonmetastatic Prostate Cancer” was recently published in the journal Annals of Internal Medicine.
The new study by researchers at the University of Toronto found that non-metastatic prostate cancer patients starting or continuing ADT had significantly less BMD loss when they were given bisphosphonates (a class of medicines that slow down or prevent bone loss) and Prolia (the only FDA-approved therapy for cancer treatment-induced bone loss), compared with those receiving a placebo, normal care, or other active treatments.
The review set out to evaluate the effectiveness of drug, supplement, and lifestyle interventions currently employed as measures to prevent fractures, improve BMD, and delay osteoporosis in non-metastatic prostate cancer patients. Bisphosphonates were found to increase BMD over a placebo, but had no effect at preventing fractures among patients with non-metastatic prostate cancer. Prolia, administered subcutaneously every six months in a 60 mg concentration, improved BMD and reduced the incidence of new vertebral fractures, according to the results of one clinical trial.
According to Dr. David Samadi, MD, chairman of urology at New York’s Lenox Hill Hospital, “this study should remind all urologists of the gap in regards to bone health care for men with prostate cancer. More testing of bone mineral density both before and during ADT treatment is an important step in identifying those men who may be at risk. One beginning step is to do a risk assessment tool evaluating men with prostate cancer receiving ADT and educating them on the adverse effects of ADT. We also need to be mindful of talking to our patients about their diet and lifestyle making sure they are getting adequate sources of calcium and exercising regularly,” Samadi said.
I have been on a vacation but am now resuming publishing pertinent posts.
As has been written before, several potential side effects accompany hormonal therapy for prostate cancer. A MedlinePlus e mail received today from the National Institutes of Health (NIH) National Library of Medicine discussed the potential heart risk posed by early hormone suppression treatment of prostate cancer. The take-home message from a new study is that “patients with localized prostate cancer should be followed to minimize the health effects of androgen-deprivation therapy on the cardiovascular system,” said study author Reina Haque, a researcher with the Kaiser Permanente Southern California Department of Research & Evaluation. The advice given is that “patients should consider heart-healthy lifestyle changes, and physicians should actively monitor the patient’s health for early signs of heart disease.”
In recent years, there’s been an expansion in use of hormone-suppressing treatment for prostate cancer. The treatment was previously restricted to advanced prostate tumors, but now it’s being given to a growing number of men with early stage prostate cancer that has not spread to other parts of the body. However, the safety and effectiveness of androgen-deprivation therapy for these men hasn’t been investigated, the study authors said.
In the new study, researchers assessed outcomes for more than 7,600 men with early stage prostate cancer. The investigators tracked the men for up to 12 years, starting when they were diagnosed between 1998 and 2008. The researchers factored in certain heart risk factors — things such as overweight/obesity, history of smoking, diabetes, high blood pressure or if they required heart medications. The study found the men with early stage prostate cancer who did not already have heart disease, but who received hormone-depleting treatments had an 81 percent higher risk for heart failure. Meanwhile, those who already had heart disease when they received the anti-hormone treatment also had a greater risk for heart rhythm problems, including a 44 percent increased risk of an irregular heartbeat. These men were also three times more likely to develop “conduction disorder,” which occurs when electrical impulses to the heart are interrupted.
The findings allow men with localized prostate cancer to consider the positive and negative effects of androgen-deprivation therapy and discuss it with their physicians. “If they move forward with the therapy, patients should work with their physicians to adjust their lifestyle to reduce the risk of cardiovascular disease.”
On May 15th, this website posted information about a Phase 1-2 clinical trial sponsored by the National Cancer Institute (NCI) of the National Institutes of Health (NIH). The proposed therapeutic regimen initially consisted of the NCI vaccine PROSTVAC, and two antibodies, ipilimumab (Yervoy®) and nivolumab (OPDIVO®). However, toxic events recently surfaced in the use of ipilimumab in several patients necessitating its removal from this particular NCI trial. In addition, a website post dated April 11th, 2017 cited the lack of activity of ipilimumab as a sole agent in prostate cancer clinical trials. However, it was proposed that ipilimumab might be more useful in combination immunotherapy.
Psalm 93 states:
1 The Lord reigns, he is robed in majesty;
the Lord is robed in majesty and armed with strength;
indeed, the world is established, firm and secure.
2 Your throne was established long ago;
you are from all eternity.
3 The seas have lifted up, Lord,
the seas have lifted up their voice;
the seas have lifted up their pounding waves.
4 Mightier than the thunder of the great waters,
mightier than the breakers of the sea—
the Lord on high is mighty.
5 Your statutes, Lord, stand firm;
holiness adorns your house
for endless days.
Iguazu Falls, (see this link) on the border of Brazil and Argentina, is a spectacular waterfall system of 275 falls along 2.7 km (1.67 miles) of the Iguazu River. Etched on a wall on the Brazilian side of the Falls are the words of Psalm 93:4, “Mightier than the thunders of many waters, mightier than the waves of the sea, the Lord on high is mighty!” Below it are these words, “God is always greater than all of our troubles.”
The writer of Psalm 93, who penned its words during the time that kings reigned, knew that God is the ultimate King over all. “The Lord reigns,” he wrote. “Your throne was established long ago; you are from all eternity” (vv. 1–2). No matter how high the floods or waves, the Lord remains greater than them all.
The roar of a waterfall is truly majestic, but it is quite a different matter to be in the water hurtling toward the falls. That may be the situation you are in today. Physical, financial, or relational problems loom ever larger and you feel like you are about to go over the falls. In such situations, the Christian has Someone to turn to. He is the Lord, “who is able to do immeasurably more than all we ask or imagine” (Eph. 3:20) for He is greater than all our troubles. You can pray “Lord, I know that You are powerful and greater than any trouble that might come my way. I trust You to carry me through.”
Never measure God’s unlimited power by your limited expectations.
Are there areas in your life that feel out of control? If so, you’re in good company. So many of the psalms were inspired by desperate feelings of fear and confusion. Yet they ended up as songs of hope in the God who has promised to never leave us or forsake us. But who is this God? The author of Psalm 93 identifies Him as the Lord (Yahweh). By contrast to legendary gods of war, fertility, weather, travel, or the hunt, He is the God who created the heavens and the earth (Gen. 2:4).
Consider the implications of such a Creator. Use the measure of modern astronomy. What kind of God speaks into existence billions of galaxies filled with trillions of suns far greater than our own? Yet even the cosmos is not the measure of His greatness. According to the New Testament (John 1:1–3, 14), the God of the Bible is the Lord who, in Jesus, showed that He is greater than our troubles by bearing our sins and diseases. In the weakness of His crucifixion and by the power of His resurrection, He showed that even His love for us is greater than our sin and life’s troubles whatever they may be. For information of how to have a personal relationship with such a Creator, see the following link.
The above was an excerpt from Our Daily Bread Devotional of July 19th, 2017, published by RBC Ministries.
If You Are Taking Taxotere for Prostate Cancer, This Blog on Minimizing Hair Loss May Be of Interest.bjgabrielsen : July 25, 2017 2:43 am : 2017
The Food and Drug Administration (FDA) has cleared a cooling cap—a device designed to reduce hair loss during chemotherapy—for use by patients with any kind of solid tumor. FDA initially cleared the device, the DigniCap® Scalp Cooling System, for patients with breast cancer in 2015. The expanded clearance of DigniCap is for “reducing the frequency and severity of hair loss” in adult patients with solid tumors who are receiving chemotherapy types and doses that are associated with this common side effect.
Scalp cooling, which has been used in Europe for several decades, is thought to prevent hair loss by reducing blood flow to hair follicles. Cooling the scalp causes blood vessels to constrict, which may limit the amount of chemotherapy drug that reaches hair follicles.
The DigniCap system uses a tightly fitted cap in which cold liquid circulates to cool the scalp before, during, and after chemotherapy. This cap, which is connected to a machine that regulates the cooling process, is covered by an outer cap, made of neoprene, that acts as an insulator.
The average total cost of scalp cooling ranges between $1,500 and $3,000 per patient, depending on the number of cycles of chemotherapy. Insurance does not currently cover scalp cooling treatments, according to the maker of DigniCap, Dignitana Inc., of Sweden.
For the full article, see the following link published by the National Cancer Institute.
Testing for two biomarkers in urine may help some men avoid having to undergo an unnecessary biopsy to detect a suspected prostate cancer, findings from a new study show.
In the NCI-supported study, researchers from Emory University in Atlanta and M.D. Anderson in Houston tested urine samples from men referred for a prostate biopsy for elevated levels of two biomarkers (RNA biomarkers called PCA3 and T2:ERG) that studies have shown are associated with aggressive prostate cancer. Restricting biopsies to only those men with elevated levels of either of the biomarkers would have reduced the number of these unnecessary biopsies by an estimated one-third to one-half, the researchers report May 18 in JAMA Oncology.
At the same time, this pre-biopsy screening approach would still “preserve the ability to detect the more aggressive cancers,” explained the study’s lead investigator, Martin Sanda, M.D., of the Emory University Winship Cancer Institute.
The PCA3 gene is expressed at high levels in prostate cancers, and a urine test for PCA3 RNA is commonly used in clinical practice to monitor for potential disease in men who have a negative biopsy following an abnormal PSA test or digital rectal exam, Dr. Sanda explained. There is also a urine test for T2:ERG, which is the result of a fusion, or translocation of parts of two different genes, TMPRSS2 and ERG. This translocation is found in approximately half of advanced prostate cancers. Currently, the T2:ERG test is only available at a few academic cancer centers.
Currently, there are hurdles to implementing this testing in everyday care, Dr. Sanda cautioned. But the study findings “clearly demonstrate” that testing for these biomarkers could help to address some of the limitations of the current paradigm for prostate cancer screening and early detection, he said. Implementing this pre-biopsy testing in clinical practice may not yet be practical because of the limited availability of the T2:ERG test.
One of the biggest challenges for researchers has been identifying a way to screen for prostate cancer that can differentiate between indolent and potentially life-threatening cancers. One approach being tested is to develop ways to better triage care decisions following an abnormal PSA test, including making more informed decisions about whether to pursue a biopsy. Prostate biopsies have risks, including pain, bleeding, and potentially serious infections. The resulting oversiagnosis and overtreatment of indolent prostate cancers identified via biopsy have their own harms and costs.
You may find it useful to discuss this article and genetic testing with your urologist if you are contemplating a prostate biopsy. For a full description of the study methodology, see the full article which appeared in the June Cancer News Bulletin published by the National Cancer Institute (NCI) of the National Institutes of Health (NIH).
According to the Prostate Cancer Foundation, antioxidants play a role in the fight against cell damage and cancer development. Consuming them is highly recommended for men with prostate cancer. Different types of antioxidants can be grouped by color. For example, antioxidants in red tomatoes are identical to those in red watermelons or pink grapefruits. Antioxidants fall under six main color categories.
1) Tomatoes, pink grapefruits and watermelons contain the red antioxidant, lycopene.
2) Grapes, plums, assorted berries and pomegranates contain the red-purple antioxidant, anthocyanin.
3) Carrots, mangoes, apricots, cantaloupes, pumpkins and sweet potatoes contain the orange antioxidants alpha and beta carotenes.
4) Oranges, peaches, papaya and nectarines contain the orange-yellow antioxidant beta-cryptoxanthin.
5) Spinach, collard, yellow corn, green peas and avocados contain the yellow-green antioxidants lutein and zeaxanthin.
6) Broccoli, brussel sprouts, cabbage, kale and bok choy contain the green antioxidants sulforaphane, isothiocyanates and indoles.
7) Garlic, onions, asparagus, leeks, shallots and chives contain the white-green antioxidants allyl sulfides.
The last post discussed the concept of vaccines for prostate cancer. The second part of the PCF trilogy is an overall simplified view of the immune system, including the various cell types and how they work under both normal and cancerous conditions. This section also describes checkpoint inhibitors and how they are being developed to fight prostate cancer among other types. I again will not summarize the article here but refer the reader to the well-written review in the following link.
The third section describes checkpoint inhibitors in detail focusing on successful applications as well as those scenarios wherein their effects were less than desired. While prostate cancer is the main focus, application to other cancers is also discussed.