'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.”


ADT Plus Chemo Ideal for Oligometastatic Prostate Cancer

“Oligometastatic prostate cancer is optimally treated with the combination of docetaxel and androgen deprivation therapy (ADT), according to a presentation at the 7th European Multidisciplinary Meeting on Urological Cancers (EMUC).

“ ‘Oligometastatic disease is a transit state of prostate cancer and is an imaging technique-dependent definition,’ Bertrand Tombal MD, PhD, Chairman of the Division of Urology, Universite Catholique de Louvain, Brussels, Belgium, explained at the conference. ‘Nevertheless, it is unlikely that metastases targeted treatment will be enough to control the disease.’ “


Androgen Deprivation Therapy Associated with Increased Risk for Fatal Heart Attack

“Long term follow up indicates that men with comorbidity, predominately a prior heart attack, who received androgen deprivation therapy (ADT) died earlier, due to a fatal heart attack.

“Androgen deprivation therapy (ADT) and radiation therapy (RT) is known to prolong survival in men with unfavorable-risk prostate cancer and is considered a standard of care. However, in 2008, the FDA implemented a black box warning about ADT use for prostate cancer due to evidence that suggested an increased risk in non-fatal cardiovascular events. The association of ADT use and fatal heart attacks has remained uncertain until now. Specifically, long term follow up of a randomized clinical trial that compared ADT and radiation therapy (RT) to RT alone finds that men with significant comorbidity; most commonly prior heart attack, who received ADT died earlier, due to a fatal heart attack, compared to men who did not receive ADT.”


Statins at Start of Androgen Deprivation Therapy Increase Treatment Efficacy

“Statin use has been associated with improved outcome in prostate cancer. In a study reported in JAMA Oncology, Harshman et al found that statin use at the time of initiation of androgen-deprivation therapy was associated with prolonged time to progression during androgen-deprivation therapy in men with hormone-sensitive prostate cancer. The potential mechanism of this effect may be statin competitive inhibition of dehydroepiandrosterone sulfate (DHEAS) uptake.

“Androgen-deprivation therapy for biochemical or metastatic recurrence or new metastatic disease between January 1996 and November 2013 showed that 283 men (31%) were taking statins at the start of androgen-deprivation therapy. After a median follow-up of 5.8 years, 644 patients (70%) had disease progression while receiving androgen-deprivation therapy, with a median time to progression during androgen-deprivation therapy of 20.3 months. Median time to progression was 27.5 months (95% confidence interval [CI] = 21.1–37.7 months) in statin users vs 17.4 months (95% CI = 14.9–21.1 months) in nonusers (P < .001).”


ASCO 2015: Notable Reports on Prostate Cancer Treatment


This year’s American Society of Clinical Oncology (ASCO) annual meeting was short on any truly exciting developments in prostate cancer treatment. In stark contrast to other cancers, such as lung, breast, kidney, and melanoma, there were no reports of note on targeted and immunotherapies in prostate cancer. The two presentations summarized here offered new strategies in chemotherapy. Continue reading…


Addition of Chemotherapy Drugs to Androgen Suppression Improves Relapse-Free Survival in High-Risk Localized Prostate Cancer

“In a French phase III trial (GETUG 12) reported in The Lancet Oncology, Fizazi et al found that the addition of docetaxel and estramustine (Emcyt) to androgen-deprivation therapy (ADT) improved relapse-free survival among patients with high-risk localized prostate cancer…

“In the open-label trial, 413 patients with treatment-naive disease and at least one risk factor (stage T3-T4, Gleason score ≥ 8, prostate-specific antigen [PSA] concentration > 20 ng/mL, or pathologic node-positive disease) underwent staging pelvic lymph node dissection and were randomized to ADT (goserelin 10.8 mg every 3 months for 3 years) plus four cycles of docetaxel 70 mg/m2 on day 2 and estramustine 10 mg/kg/d on days 1 to 5 every 3 weeks (n = 207) or ADT alone (n = 206). Local treatment was administered at 3 months. The primary endpoint was relapse-free survival in the intention-to-treat population. Follow-up for other endpoints is ongoing.

“The chemotherapy and ADT alone groups were balanced for age (median 62 and 62 years), Gleason score (42% and 43% ≥ 8), pathologic node-positive status (29% in both), and serum PSA level (> 20 ng/mL in 59% in both).”