Steroid Use With Abiraterone Offers Multidimensional Benefits to Patients With mCRPC

Excerpt:

“For decades, the standard of care for men with advanced prostate cancer has been the depletion or inhibition of androgens. While androgen-deprivation therapy (ADT) often results in temporary tumor regression or symptom relief in some patients, disease progression ultimately occurs over time. For patients with metastatic disease, the median overall survival (OS), until very recently, had been less than 2 years after chemotherapy.

“While tumor progression with ADT was previously believed to be hormone-refractory or androgen-independent, a large body of evidence supports that metastatic castration-resistant prostate cancer (mCRPC) is commonly driven by elevated steroid synthesis, increased expression or splice variants of the androgen receptor (AR), or AR ligand promiscuity, indicating the ongoing need for targeted androgen therapies.”

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Common Prostate Cancer Treatments Suppress Immune Response and May Promote Relapse

Excerpt:

“Prostate cancer patients and their doctors may want to think twice about the best timing for chemotherapy or radiation therapy in conjunction with a common nonsurgical treatment, based on international research findings led by UT Southwestern Medical Center investigators.

“Researchers using mouse models found that many medical androgen deprivation therapies (ADTs) – the most commonly used nonsurgical treatments for prostate cancer – may suppress patients’ adaptive immune responses, preventing immunotherapies from working if both treatments are used but not sequenced properly. ADTs are anti-hormone therapies that decrease the body’s levels of androgens, the type of hormone that is required for prostate cancer to survive and grow.

“The study findings were published this week in Science Translational Medicine.”

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Intermittent Hormonal Therapy Proves to be Viable in Prostate Cancer

“With no significant difference between intermittent and continuous androgen-deprivation therapy, patients with prostate cancer may experience an improvement in their quality of life with the former.

“Androgen-deprivation therapy may be an effective treatment in prostate cancer, though its side effects may result in a loss of quality of life for patients. Allowing low-risk patients to take breaks between treatments—a practice known as intermittent hormonal therapy, or a ‘hormone holiday’—may combat these challenges without impacting survival.

” ‘Intermittent hormonal therapy has been growing in popularity over the years. Patients who receive hormone therapy often have side effects, and giving them so-called “hormone holidays” may improve quality of life. Over the years, there has really been a lot of trials and experimental work that laid the groundwork for this going back 20 years,’ said Leonard G. Gomella, MD, in an interview with Targeted Oncology.”


“Hormone Holiday” Can Improve QoL for Select Patients With Prostate Cancer

“Androgen-deprivation therapy, while an effective treatment for prostate cancer, can result in side effects and a reduced quality of life. Allowing low-risk patients to take breaks between treatments—a practice known as intermittent hormonal therapy, or a ‘hormone holiday’—may combat these challenges without impacting survival.

“A recent systematic review and meta-analysis conducted by JAMA Oncology found no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients).”


Metastatic Hormone-Sensitive Prostate Cancer Should Include Docetaxel Alongside ADT

“Treatment initiation for hormone-sensitive metastatic prostate cancer should include the addition of docetaxel to androgen deprivation therapy (ADT) as standard of care. This recommendation is based on a meta-analysis1 of three large, relatively recent, randomized trials showing that docetaxel improves survival and failure-free survival (FFS) in metastatic hormone-sensitive prostate cancer. These findings move docetaxel up to the hormone-sensitive setting from its previous role as upfront treatment in the castrate-resistant setting.

“In men with metastatic hormone-sensitive prostate cancer, docetaxel added to ADT improved 4-year survival by an absolute value of 9% and reduced FFS by an absolute value of 16%.”


'Bipolar' Therapy: New Twist in Advanced Prostate Cancer

“Preliminary data suggest that a new twist on manipulating hormones in prostate cancer shows some benefit. The standard approach to treatment is androgen deprivation therapy (ADT), but the new approach intersperses this with bipolar androgen therapy (BAT) with intramuscular testosterone injections.

“Results from a small phase 2 study in 29 men with advanced hormone-sensitive prostate cancer show that the primary endpoint was met, with nearly 60% of men achieving a prostate-specific antigen (PSA) level <4 ng/mL after undergoing two cycles of BAT.

“The findings, which were presented at Genitourinary Cancers Symposium (GUCS) 2016, also suggest that BAT may have a positive impact on quality of life.”


Long-term Toxicity Surprise With ADT for Prostate Cancer

“In a surprising study result, the use of intermittent androgen-deprivation therapy (ADT) for prostate cancer is not associated with fewer long-term adverse events than continuous ADT.

“The outcome was unexpected because it was hypothesized that the intermittent schedule, which gives patients a break from the treatment, would be less harmful.

“ADT is a cornerstone of locally advanced and metastatic prostate cancer treatment, but is associated with an array of adverse events, including sexual dysfunction, bone demineralization, cardiovascular disease, metabolic complications, cognitive changes, and diminished quality of life.”


Comparing Chemical and Surgical Castration for Prostate Cancer

“Surgical castration to remove the testicles (orchiectomy) of men with metastatic prostate cancer was associated with lower risks for adverse effects compared with men who underwent medical castration with gonadotropin-releasing hormone agonist (GnRHa) therapy, according to an article published online by JAMA Oncology.

“Androgen-deprivation therapy (ADT), which is achieved through surgical or medical castration, has been a cornerstone in the management of  (PCa) for the past 50 years. But the use of bilateral orchiectomy has been nearly eliminated in the U.S. because of cosmetic and psychological concerns.

“Quoc-Dien Trinh, M.D., of Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, and coauthors compared adverse effects of GnRHa and bilateral orchiectomy in 3,295 men with metastatic PCa (66 or older) between 1995 and 2009. The authors analyzed six major adverse effects, which were picked based on their effect on a patient’s quality of life, the potential for increased health care costs, and on a previously described association with ADT use. The six  were: any fractures, peripheral artery disease, venous thromboembolism, cardiac-related complications, diabetes and cognitive disorders.”


Hormone Therapy for Prostate Cancer Tied to Possible Alzheimer's Risk

“Hormone therapy for prostate cancer might dramatically increase a man’s risk of developing Alzheimer’s disease, a large-scale analysis of health data suggests.

“Men who underwent  (ADT) for their prostate cancer had nearly twice the risk of Alzheimer’s, when compared to prostate cancer patients who didn’t receive hormone therapy, researchers found.

“The risk increased even more if men received hormone therapy for longer than a year, said study lead author Dr. Kevin Nead, a radiation oncology resident at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.”