POSTED: July 31, 2017

Xtandi V. Zytiga: Cognitive Effects?

Alicia Morgans, M.D., Hematology/Oncology

 photos by Susan Urmy


Dr. Alicia Morgans, a medical oncologist, specializes in treating advanced prostate cancer and is particularly interested in addressing treatment side effects.

In July, Prostatepedia spoke with her about her clinical trial that looks at the cognitive effects that Xtandi (enzalutamide) and Zytiga (abiraterone) can have.



Dr. Alicia Morgans: My research focuses on understanding the complications of cancer survivors and, specifically, understanding the complications of hormonal manipulation in men with prostate cancer. I’ve done work investigating osteoporosis and bone complications, cardiovascular complications, and metabolic complications like diabetes. The one area that I had not really explored, and that has been underexplored in the field, is the possibility that there may be cognitive changes associated with the hormonal therapies we use.

A patient who served as an inspiration for the study was a preacher who I met a few years ago, just a few weeks after his urologist started him on Xtandi (enzalutamide). His family was concerned because he developed a profound change in his motivation and planning skills, and he was unable to give sermons since starting the medication.

We were able to stop the medication, and a few weeks later, everyone said that he was back to normal. I just needed to understand why this might be the case. This led to the development of our study.

We are comparing the cognitive function of men starting Zytiga (abiraterone) or Xtandi (enzalutamide) over time to see if there is any difference between drugs that block the androgen receptor like Xtandi (enzalutamide) and drugs that just lower testosterone levels more completely like Zytiga (abiraterone).

Both of these drugs are used in the same patient population and are tremendously effective at controlling the cancer, so this comparison could be done safely.

I was fortunate to have some incredible collaborators with experience in traditional neurocognitive testing help develop the study protocol. In addition to comparing cognitive function between groups, the study validates a computer-based cognitive testing system (Cogstate) against traditional neurocognitive pen-and paper tests in the prostate cancer population. If the measures appear to provide similar assessments, I hope to integrate computer-based cognitive testing into many prospective therapeutic studies just as patient reported outcome measures of pain, fatigue, and depression have been.

Finally, I have to mention that we were very fortunate to pique the interest of the Prostate Cancer Foundation in this work, and they were incredibly generous in conferring an award to fund the study.

Their award allowed us to integrate an assessment of possible genetic predisposition to developing cognitive dysfunction. The award also provides funds to integrate advanced neuroimaging with a noninvasive MRI series into the protocol. This will enable us to look at structural and functional changes that may happen in the brain during treatment.

We are doing this trial now because it is definitely an area of clinical concern in my practice. I don’t think that previous work has been able to nail down which populations are at highest risk for cognitive dysfunction or develop a methodology that is both reliable and reproducible in larger scale settings. Our trial design may validate a computer-based methodology that can be expanded to other sites without requiring that trials include psychologists with neurocognitive expertise to administer cognitive tests. The computer-based method is less resource-intensive and more easily scalable.

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3 Comment

robbie boyes

Good idea, having had a prostatectomy, radio treatment,Lucrin and now on Lucrin + Enzalutamide there is no doubt ones cognitive ability changes. If it buys us time then it has to be put up with.

Posted: Aug 10, 2017

owen carlin

I am a long term prostate cancer ( metastatic bone) and have been on many of Dr. Meyers
past treatments including forms of radiation. and am now on Xtandi. However I cannot
stand more than one per day and two per day three times per week. (10 per week total.)
Why? They fog my brain. I am not a rocket scientist ,but an 85 year retiree and I
have a wife ,home, and personal finances to take care of . Thank You Owen Carlin

Posted: Aug 06, 2017

Greg C

I was diagnosed with PCa in 2010 at age 47 year old.
Prostatectomy 7/2010 PSA Presurgery=42 Post=28 (mCRPCa)
Post surgery – Lupron (every 3 mo.)+ 14 weeks Radiation
CT scans every 6 mo. all clean except Kidney Cancer (unrelated to PCa) surgery in 2/2016
PSA Increasing 6/1/15=0.05 – 1/1/17=3.22 (on Lupron from 7/2010 to present)
Started Zytiga 2/10/17
PSA Decreasing 2/14/2017=2.89 – 6/9/2017=0.18

For the first 5 years, I had serious fatigue and hot flashes and the onset of metabolic syndrome (mostly diabetes). In the last 2 years, the hot flashes are much decreased but the fatigue has continued. After being on Zytiga for 5 months the fatigue has increased but I have not had any other significant side effects. I am sure that I have had a cognitive decline all along but I can’t quantify the level.

Posted: Aug 04, 2017

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