ADT Plus Docetaxel for Prostate Ca: Home Run or Foul Ball?

“A ‘home run’ in advanced prostate cancer did not clear the fence in a second evaluation of androgen deprivation therapy (ADT) with docetaxel, according to a study reported here.

“An updated analysis of a French study showed that adding chemotherapy to ADT did not significantly improve overall survival for men with hormone-sensitive, metastatic prostate cancer. However, the 13-month difference in favor of the docetaxel arm was comparable to the statistically significant 14-month improvement observed in a larger U.S. trial reported last year.

“The French study also failed to show a survival benefit in patients with high-volume disease, which accounted for two-thirds of the patients in the U.S. trial.

” ‘We are awaiting the analysis of [a third randomized trial], and we hope to come up with a common analysis of the three studies altogether in order to give the good [best] treatment for the good [best] patient,’ Gwenaelle Gravis, MD, of Institut Paoli-Calmettes in Marseilles, France, said here at the Genitourinary Cancers Symposium.

“For more than 40 years, ADT has represented standard of care for metastatic hormone-sensitive advanced prostate cancer. The emergence of effective chemotherapy for castration-resistant prostate cancer led to speculation that use of cytotoxic therapy in hormone-sensitive advanced prostate cancer might improve outcomes as compared with ADT alone.”


Provenge Induces Sustained Immune Response Even at 2 Years after Treatment

“Preliminary results from the phase II STAND trial have demonstrated a robust immune response with sipuleucel-T (Provenge) that continues 2 years after completing treatment in men with biochemically recurrent prostate cancer. The findings, along with data from an ongoing phase IV registry related to increasing enrollment of African Americans in prostate cancer trials, are being presented at the 2015 Genitourinary Cancers Symposium, held February 26 to 28 in Orlando…

“The STAND study (Abstract 171) is a randomized, phase II trial that consisted of two patient study groups. One group completed sipuleucel-T 2 weeks before initiation of androgen-deprivation therapy, and the second received the drug 3 months after the start of androgen-deprivation therapy. Preliminary results from STAND indicate that immune responses were observed in both study arms and suggest there may be a greater cellular immune response in patients who received sipuleucel-T prior to androgen-deprivation therapy. Humoral immune responses were observed and similar between both treatment arms.

“ ‘It is very encouraging to observe that [sipuleucel-T] provides an immune response in men with biochemical-recurrent prostate cancer long after the course of androgen deprivation therapy has ended,’ said Neal Shore, MD, Medical Director at the Carolina Urologic Research Center. ‘This study may also provide guidance on the optimal sequencing of immunotherapy and androgen-deprivation therapy in biochemical-recurrent prostate cancer.’ ”


Adding Radiotherapy to Androgen Deprivation in Advanced Prostate Cancer Prolongs Survival by More than One Year

“An 8-year analysis confirmed that adding radiotherapy to androgen deprivation therapy (ADT) in men with locally advanced prostate cancer improved overall survival and reduced the risk of prostate cancer–specific death. The median overall survival was 10.9 years in the combination arm compared with 9.7 years in the ADT-alone arm.

“This final analysis is published in the Journal of Clinical Oncology.

“The original results of this international NCIC Clinical Trials Group PR.3 trial were published in the Lancet  in 2011. This prior interim analysis showed a significant improvement in overall survival for those in the ADT plus radiotherapy treatment arm (hazard ratio [HR] = 0.77; P = .033). Based on the results, radiotherapy was recommended as part of the standard therapy for prostate cancer.

“The NCIC trial is the largest study investigating the addition of radiotherapy to ADT.”


Now BATting: A New Treatment Approach That Uses Testosterone First, Then ADT


Androgen deprivation therapy (ADT) has long been a mainstay in the management of prostate cancer. Indeed, the vast majority of prostate cancers depend on androgens (hormones like testosterone) for their growth. Lowering testosterone levels with ADT is a reasonable approach. But it comes with two sets of problems. Continue reading…


ADT Before or After Surgery Gives Similar Survival Rates in Prostate Cancer

The gist: Recent research found that prostate cancer patients have similar survival rates whether they have androgen deprivation therapy (ADT) before or after tumor-removal surgery. The study focused on men with intermediate- or high-risk prostate cancer who were treated between 1995 and 2002.

“Patients with intermediate- or high-risk prostate cancer demonstrated similar biochemical relapse-free survival, distant metastasis-free survival and OS regardless of whether they received androgen deprivation in the neoadjuvant or adjuvant settings, according to study results.

“Patients with localized prostate cancer typically undergo androgen deprivation therapy (ADT) in the neoadjuvant setting, concurrent with radiation therapy.

“Michael A. Weller, MD,of Cleveland Clinic, and colleagues assessed whether patients who underwent ADT in the adjuvant setting experienced different outcomes.

“The analysis included 515 patients treated with radiation therapy and ADT from 1995 to 2002. Of these patients, 311 underwent ADT in the neoadjuvant setting, beginning 2 to 3 months before the start of radiation therapy. The other 204 patients underwent ADT in the adjuvant setting, immediately after the completion of radiation therapy.”


German Agency: Provenge No Better than Watchful Waiting, Standard Hormone Therapy for Some Men with Metastatic Prostate Cancer

The gist: The drug sipuleucel-T (Provenge) may be no better than watchful waiting and standard androgen deprivation therapy for certain prostate cancer patients. That was the conclusion of the German Institute for Quality and Efficiency in Health Care (IQWiG). The IQWiG analyzed data on men with metastatic prostate cancer who had few or no symptoms and did not yet need chemotherapy.

“Sipuleucel-T (trade name Provenge) has been approved since September 2014 for men with metastatic prostate cancer who have few or no symptoms and do not yet require chemotherapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether the drug offers patients an added benefit over one of the appropriate comparator therapies.

“According to the findings, an added benefit is not proven: The data on mortality were not evaluable because differences between the treatment groups might have been caused by the circumstances of the subsequent therapies. At the same time, certain side effects such as fever occur more frequently.

“Treatment with sipuleucel-T aims to stimulate the immune system to kill cancer cells. Immune cells are extracted from the patient’s blood and treated with a protein in a laboratory. These treated cells are then injected back into the patient’s blood where they are supposed to better recognize cancer cells and stimulate the immune system to fight the prostate cancer.

“Sipuleucel-T is an option for patients whose cancer has already formed metastases and can also no longer be influenced by blocking the hormone testosterone (hormone refractory).”


Common Prostate Cancer Treatment Associated with Decreased Survival in Older Men

“A common prostate cancer therapy should not be used in men whose cancer has not spread beyond the prostate, according to a new study led by researchers at Henry Ford Hospital.

“The findings are particularly important for men with expectancies because the exposes them to more adverse , and it is associated with increased risk of death and deprives men of the opportunity for a cure by other methods.

“The research study has been published online in European Urology.

“The focus of the new study is androgen deprivation therapy (ADT), in which an injectable or implanted medication is used to disrupt the body’s ability to make testosterone. ADT is known to have significant side effects such as heart disease, diabetes, increased weight gain and impotence; however a growing body of evidence suggests ADT may in fact lead to earlier death.

“Since the 1940s, the therapy has been a mainstay of treatment for prostate cancer that has metastasized, or spread beyond the . Still other studies support the use of ADT when it is used as an adjuvant, or in addition to, for higher risk prostate cancer. No evidence exists to support the exclusive use of ADT for low risk or localized prostate cancer.”


Men Treated with Enzalutamide Experienced a 17-Month Delay in the Time to Initiation of Chemotherapy Compared to Placebo

The gist: Prostate cancer patients in the EU can now be treated with the drug enzalutamide (aka XTANDI). The European Commission approved the drug for adult men with metastatic castration-resistant prostate cancer (nCRPC) who have no symptoms or mild symptoms after failed treatment with androgen deprivation therapy, and who are not yet eligible for chemotherapy treatment. In a clinical trial with volunteer patients, enzalutamide gave men 17 extra months before chemotherapy was needed.

“Astellas Pharma Europe Ltd. today announced that the European Commission (EC) has granted a variation to amend the Marketing Authorisation for enzalutamide (trade name XTANDI).1 Enzalutamide is now approved in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.1

“ ‘Enzalutamide provides a viable treatment option for a broad population of men with mCRPC, regardless of age, or their readiness for chemotherapy, which provides a meaningful period of time during which men have their disease controlled without the need for chemotherapy’, said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of Urology and Professor of Physiology, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. ‘The decision from the European Commission to approve enzalutamide, an effective and well tolerated alternative to chemotherapy, is a very important milestone for men with prostate cancer that has advanced.’

“The Marketing Authorisation approval is based on results from the pivotal phase III PREVAIL study which demonstrate that enzalutamide improves outcomes for men with advanced prostate cancer who have not received chemotherapy.2″


Prostate Cancer Medications Linked with Increased Risk of Heart-Related Deaths in Men with Cardiovascular Problems

“A new study has found that certain prostate cancer medications are linked with an increased risk of dying from heart-related causes in men with congestive heart failure or prior heart attacks. Published in BJU International, the findings will help doctors and patients weigh the benefits and risks of the drugs.

“Androgen deprivation therapy (ADT), which reduces levels of male hormones in the body to prevent them from stimulating cancer cells, is a mainstay of treatment for prostate cancer. Despite its anticancer effects, ADT has been associated with heart problems, including increased risk of diabetes, coronary heart disease, heart attacks, and sudden cardiac death. To investigate this potential link thoroughly, Paul Nguyen, MD, of the Dana-Farber/Brigham and Women’s Cancer Center in Boston, along with David Ziehr of Harvard Medical School and their colleagues, analyzed information on 5,077 men with prostate cancer who were treated between 1997 and 2006. Thirty percent of these men received ADT, while the others did not.

“After a median follow-up of 4.8 years, no association was detected between ADT and heart-related deaths in men with no cardiac risk factors (1.08 percent at five years for ADT versus 1.27 percent at five years for no ADT) or in men with diabetes, hypertension, or high cholesterol (2.09 percent vs 1.97 percent). However, ADT was associated with a 3.3-times increased risk of heart-related deaths, in men with congestive heart failure or prior heart attacks. In this subgroup, heart-related deaths occurred in 7.01 percent of men receiving ADT versus 2.01 percent of men not receiving after five years. This suggests that administering the therapy to 20 men in this potentially vulnerable subgroup could result in one cardiac death.

” ‘While androgen deprivation therapy can be a lifesaving drug for men with prostate cancer and significantly increase the cure rates when used with radiation for aggressive disease, this study also raises the possibility that a small subgroup of men who have significant heart disease could experience increased cardiac death on ADT,’ said Dr. Nguyen. He noted that because the study was retrospective, it must be carefully weighed against larger controlled trials that have demonstrated the benefits of ADT. ‘I would still say that for men with significant heart problems, we should try to avoid ADT when it is not necessary—such as for men with low-risk disease or men receiving ADT only to shrink the prostate prior to radiation. However, for men with high-risk disease, in whom the prostate-cancer benefits of ADT likely outweigh any potential cardiac harms, ADT should be given even if they have heart problems, but the patient should be followed closely by a cardiologist to ensure that he is being carefully watched and optimized from a cardiac perspective.’ “