Enzalutamide versus Abiraterone Acetate/Prednisone

[pjoshea13]

New French study below [1].

It is well-known that there is overlap in the reasons why resistance to Enzalutamide [Xtandi] & Abiraterone [Zytiga] occur. This means that many will see little added benefit from the two drugs taken sequentially. So which drug to opt for if given the choice?

Abiraterone works via a scorched-earth attack on all hormones in the steroid cascade below progesterone & pregnenolone, whereas Enzalutamide is a direct androgen receptor antagonist. In the distant past, many prefered Bicalutamide [Casodex] monotherapy to ADT.

However, men on Enzalutamide may experience a loss of motivation to explore, & maybe cognition difficulties too ...

... according to a new mouse study ...

due to: "decreased tyrosine hydroxylase (TH)-dopaminergic activity in the substantia nigra pars compacta and the ventral tegmental area. A decrease in TH+-DA afferent fibers and Phospho-DARPP32-related dopaminergic neuronal activities in the striatum and the ventral hippocampus highlighted ENZ-induced dopaminergic regulation within the nigrostriatal and mesolimbocortical pathways"

We must have quite a number of members on Enza. Do these side effects resonate with you? Just answer YES or NO. Or "Don't know", which I will count as a YES.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/342...

ancers (Basel)

. 2021 Jul 14;13(14):3518. doi: 10.3390/cancers13143518.

The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice

Celeste Nicola 1 2 3 , Martine Dubois 1 2 3 , Cynthia Campart 1 2 3 , Tareq Al Sagheer 1 2 , Laurence Desrues 1 2 3 , Damien Schapman 2 4 , Ludovic Galas 2 4 , Marie Lange 3 5 6 , Florence Joly 3 5 6 7 , Hélène Castel 1 2 3 8

Affiliations collapse

Affiliations

1 Normandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, France.

2 Institute for Research and Innovation in Biomedicine (IRIB), 76000 Rouen, France.

3 Cancer and Cognition Platform, Ligue Nationale contre le Cancer, 14000 Caen, France.

4 Normandie University, UNIROUEN, INSERM, PRIMACEN, 76000 Rouen, France.

5 Centre François Baclesse, Clinical Research Department, 14000 Caen, France.

6 Normandie University, UNICAEN, INSERM, U1086 ANTICIPE, 14000 Caen, France.

7 University Hospital of Caen, 14000 Caen, France.

8 Normandie University, UNIROUEN, INSERM, DC2N, Team Astrocyte and Vascular Niche, Place Emile Blondel, CEDEX, 76821 Mont-Saint-Aignan, France.

PMID: 34298734 DOI: 10.3390/cancers13143518

Abstract

Cognitive side effects after cancer treatment threatening quality of life (QoL) constitute a major challenge in oncology. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are examples of next-generation therapy (NGT) administered to metastatic castration-resistant prostate cancer (mCRPC) patients. NGT significantly improved mCRPC overall survival but neurological side effects such as fatigue and cognitive impairment were reported. We developed a behavioral 17 months-aged and castrated mouse model receiving per os AAP or ENZ for 5 days per week for six consecutive weeks. ENZ exposure reduced spontaneous activity and exploratory behavior associated with a decreased tyrosine hydroxylase (TH)-dopaminergic activity in the substantia nigra pars compacta and the ventral tegmental area. A decrease in TH+-DA afferent fibers and Phospho-DARPP32-related dopaminergic neuronal activities in the striatum and the ventral hippocampus highlighted ENZ-induced dopaminergic regulation within the nigrostriatal and mesolimbocortical pathways. ENZ and AAP treatments did not substantially modify spatial learning and memory performances, but ENZ led to a thygmotaxis behavior impacting the cognitive score, and reduced c-fos-related activity of NeuN+-neurons in the dorsal hippocampus. The consequences of the mCRPC treatment ENZ on aged castrated mouse motivation to exploration and cognition should make reconsider management strategy of elderly prostate cancer patients.

[Grumpyswife]

Yes

[cesces]

"However, men on Enzalutamide may experience a loss of motivation to explore, & maybe cognition difficulties too"

So Abiraterone doesn't have that effect?

Sounds like a good reason to favor Abiraterone.

Is there any argument to the contrary?

[Hidden in reply to cesces]

Blood pressure increases with abi.

[RJ-MN]

On enzalutamide for 5.5 years @ NIH (off trial 09/19); not aware of any spatial or cognitive difficulties.

[Roscoaus2000 in reply to RJ-MN]

3 months on Enzalutamide and I had a seizure. I had 2 little memory lapses at 6 and 10 weeks that I ignored. After clear CT scan then clear MRI my Onc concluded the Enz had passed blood brain barrier. I have been on Aberiterone + Prednisolone for over 3 years with good control and minimum side effects.

[CAMPSOUPS in reply to Roscoaus2000]

Hey Rosco,

By the way thank you for adding a biography on your page.

You had a really good response to basically bicalutamide (Casodex) and standard ADT injections (Zoladex).

After 11 months your PSA rose from .01 to 1.0.---Did your doctor (s) communicate to you whether or not you were still hormone sensitive or did you become castrate resistant?

When you were diagnosed metastatic was it widespread skeletal bone mets and enlarged lymph nodes?

You were started on Enzalutamide (Xtandi). 3 Months. Due to seizure (blood brain barrier) episode Xtandi was stopped and you began Abiraterone (Zytiga and prednisone).

We often hear that if you start with Xtandi then Zytiga wont work and the opposite if start with Zytiga then Xtandi wont work.

In your case I guess I have to wake up and read what you wrote otherwise I am liable to ramble on in a unrelated train of thought.

I need to think of it this way. You were only on Xtandi for 3 months. Also, I don’t see any indication you were not responding to Xtandi therefore it would make sense that you would respond to Zytiga as well.

Excuse my questions. Feel free to disregard if you wish. I’m 10 years younger than you and yet can’t seem to concentrate. Have a lot of starts and stops during the day but nothing out of half a dozen things actually gets done. Lol.

[Roscoaus2000 in reply to CAMPSOUPS]

Actually, I loved Enzo. My energy level jumped and my psa dropped back to <0.001. So it worked. I had two very minor incidents when I was driving to my sons, I couldn’t remember taking a turn on a country road. I turned back 2 ks. To make sure. I did this twice 2 was apart. When I had my seizure I had just done a on. time on a Park run. They thought I may have been dehydrated, but not so. 2 weeks after starting Aberiterone I begged my Onc. To stay on Enzo because the Aberiterone was upsetting my digestion. He asked me to persevere and it did settle. My energy level was certainly less. Any way I count my blessings I am still here.Mentally I feel great. The side effects listed with Enzo include warning of blood brain barrier problem. On diagnosis I had extensive Mets right throughout my skeleton including skull. Also in lymph nodes. 4 months later the skeletal were less noticeable and the lymph were undetectable. This was using a whole body scan with some dye in my system. Haven’t had a scan since. Onc suggest considering Pet scan when psa rises to 1.00 next year and then maybe some targeted radiation.I think I am blessed to have had normal full life till 75, then less than 2 years of symptoms then back to nearly fully functioning for last 3 years. ( sex life gone forever but married life great)

[EdBar]

Yes to cognitive issues on Enzi, also experienced headaches and BP issues, but it helped keep PSA undetectable for around 6 years, only recently has PSA started to show at extremely low levels. Been on half dose of Enzi for past 2+ years due to cumulative SE’s.

Ed

[leo2634]

I've been on Zytiga for about four years now and while it definitely affects your quality of life the key word there is "Life" its keeping me alive so I deal with the challenges. I keep myself active and when I can't I listen my body and rest. The side effects are many and daily but your body and mind lean to deal with them. Never give up Never surrender. Leo

[Yank66]

Yes-memory lapses & cognitive challenges

[monte1111]

What was the question?

[Ausi]

No for me

[Beermaker]

5 years of Enza and I think I have ALL of the common SEs. I just don't seem to remember. But I am 9.5 years out and have a >= 0.01 PSA and hope to keep it there. I positively hate the ADT and Enza SEs. My onc asked if it worth it. Oh, I am on a half dose, have been for 5 years.