Prostate Cancer: Effects of Hormone Therapy on Cognitive Function Addressed in Large Study

MedicalResearch.com Interview with:

Ravi Jayadevappa, PhD, MS Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104-2676 

Dr. Jayadevappa

Ravi Jayadevappa, PhD, MS
Department of Medicine
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104-2676 

MedicalResearch.com: What is the background for this study?

Response: In the US, prostate cancer is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death among men. Research shows that hormone therapy or ADT reduces the levels of male hormones in the body, called androgens, to stop them from stimulating cancer cells to grow., and thus is effective in reducing the spread and progression of prostate cancer.

At the same time, some research has suggested that decreasing androgen levels may increase the risk factors for Alzheimer’s and dementia, including loss of lean body mass, diabetes, cardiovascular disease, and depression. The ADT therapy may lead to impaired neuron growth and the regeneration of axons, thus affecting the cognitive function. Thus there is growing interest in the possible association between exposure to ADT and cognitive dysfunction.

Our study investigates the association between exposure to ADT and subsequent diagnosis of Alzheimer’s or dementia in elderly, fee-for-service Medicare enrollees using SEER-Medicare linked databases.

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Genetic Mutation May Predict Outcomes of Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone

MedicalResearch.com Interview with:

Masaki Shiota MD, PhD Department of Urology, Graduate School of Medical Sciences Kyushu University Fukuoka , Japan

Dr. Shiota

Masaki Shiota MD, PhD
Department of Urology
Graduate School of Medical Sciences
Kyushu University
Fukuoka , Japan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  3β-hydroxysteroid dehydrogenase-1 encoded by HSD3B1 is a rate-limiting enzyme required for all pathways of dihydrotestosterone synthesis, as well as converts abiraterone into Δ4-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor.

A mutation (1245A>C) in HSD3B1 is shown to be resistant to proteasomal degradation, causing substantial accumulation of this enzyme and gain-of-function. Although the HSD3B1 (1245C) allele can be acquired by mutation, germ-line single nucleotide polymorphism (SNP; rs1047303) is also known to exist. Then, in this study, we investigated the significance of missense polymorphism in HSD3B1 gene among men treated with primary ADT or abiraterone.

The results showed men carrying variant allele showed higher risk of progression in primary androgen-deprivation therapy, but vulnerable to abiraterone treatment. Continue reading

Metastatic Prostate Cancer: Final Analysis of Adding Abiraterone Acetate (ZYTIGA® ) and Prednisone to Androgen Deprivation Therapy

MedicalResearch.com Interview with:
Kim Nguyen Chi, MD FRCPC

Professor of Medicine, University of British Columbia
Regional Medical Director, BC Cancer – Vancouver

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: For over 70 years, androgen deprivation therapy (ADT) has been the main treatment therapy for metastatic prostate cancer patients. This Phase 3 final analysis study looked at adding abiraterone acetate and prednisone to ADT for patients with metastatic prostate cancer, with the primary objectives being to assess improvements in overall survival and radiographic progression-free survival. At the first interim analysis reported in 2017, both primary endpoints were met, and the study was unblinded and patients on the ADT and placebos arm crossed over to receive ADT with abiraterone and prednisone.

This study is the final analysis reporting on overall survival. The study findings found abiraterone acetate and prednisone plus ADT continued to demonstrate an improvement in overall survival, hazard ratio (HR) = 0.66, meaning a 34% decrease in the risk of death associated with the use of ADT with abiraterone and prednisone. The median overall survival, which had not been reached before in the ADT with abiraterone and prednisone arm, was 53.3 months compared to 36.5 months for ADT plus placebo, prolonging median overall survival by 16.8 months.

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High-Risk Gleason 5 Prostate Cancers Not Resistant to Androgen Deprivation Therapy

MedicalResearch.com Interview with:

Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles

Dr. Kishan

Amar U. Kishan, MD
Assistant Professor
Department of Radiation Oncology
University of California, Los Angeles

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Three large randomized trials demonstrated an overall survival (OS) benefit when androgen deprivation therapy (ADT) is combined with radiotherapy (RT) for high-risk prostate cancer (PCa). The duration of ADT in these seminal studies ranged from six months to lifelong. Because ADT has multiple attendant adverse effects–including bone loss, altered metabolism, diminished muscle mass, gynecomastia, hot flashes, and possibly increased cardiovascular events–shortening the duration of ADT without compromising oncologic effectiveness has been an area of active study. Five trials have compared various durations of ADT, reaching conflicting conclusions with respect to overall survival outcomes, with some suggesting an improvement with longer durations of ADT and others failing to show a uniform survival benefit.

Most of these trials have amalgamated Gleason grade group 4 (Gleason score 8) PCa with Gleason grade group (GG) 5 (Gleason score 9-10) PCa. Emerging data indicate that GS 9-10 PCa constitutes a distinct subset of high-risk PCa with inferior outcomes and earlier progression than GS 8 disease. With the knowledge that GS 9-10 PCas constitute a distinct, more aggressive form of PCa, one might hypothesize that longer durations of ADT may be more advantageous in both augmenting local control and controlling potential micrometastatic disease. Alternatively, as GS 9-10 lesions by definition contain highly de-differentiated Gleason pattern 5 disease foci and may proceed to a castrate-resistant state more rapidly, one may also hypothesize that GS 9-10 lesions are less responsive to ADT, and longer durations may be counter-productive.

In order to identify differences in the impact of ADT duration on clinical outcomes of patients with GG 4 and GG 5 PCa, we performed an individual patient-level meta-analysis of six randomized trials. Our working hypothesis was that longer durations of ADT would offer significant survival benefits in both groups.

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