Should I fight for Darolutamide ? - Advanced Prostate...

Advanced Prostate Cancer

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Should I fight for Darolutamide ?

CarlosBrasil profile image
25 Replies

Thank you all so far for your advice, I am here again for some more.

After RT in a metastastic LN last year, I am again with a PSA 2.0, with a bunch of small LNs showing in the PET. RO gave up. I will start ADT again, this time with a 2nd generation added. I will restart Zoladex, and MO is adding Enzalutamide this time.

My main concern is about cognitive SEs, since I work full time as a Software Enginner, my job depends of my brain. It seems to me that Darolutimide is less harmful to the brain, due to the brain barrier question, but MO says that there was no medical evidence of that.

The issue is that insurance only pays for Darolutamide after AB, APA or Enza fails. Should I spend money and effort to go to court to try to get Darolutamide ? MO says she can prescribe, but will be hard to make a strong case.

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treedown profile image
treedown

I tried to get insurance to approve Nubeqa and failed. I got Xtandi (enza) instead and had cognitive issues as well as just about everything else. It made work very difficult for me. So I stopped it. I tried for Nubeqa a second time but Kaiser declined again. My MO said he would appeal and then decided not to without telling me why. So now I will start Zytiga again in the near future. In the meantime enjoying just Lupron so much after Xtandi its almost Iike not being on ADT at all. Also my PSA was .08 on my last test so thats two sizeable drops with Lupron only.I hope you have better luck than I did.

CarlosBrasil profile image
CarlosBrasil in reply to treedown

Thank you for sharing, I hope you keep going well in that way.

Tall_Allen profile image
Tall_Allen

The blood-brain barrier thing is only important if you have had seizures. Cognitive deficits are caused mainly by ADT, and only slightly by anti-androgens.

CarlosBrasil profile image
CarlosBrasil in reply to Tall_Allen

Got it, let's see how it goes with Enza. Thanks.

mklc profile image
mklc in reply to Tall_Allen

Good morning TA,

What are the advantages of daroludamide over the other 2nd generation drugs?

Thank you

Tall_Allen profile image
Tall_Allen in reply to mklc

Certainly a good choice if you are epileptic. It doesn't activate the GABAA receptor, so it may not cause as much drowsiness, but that is unproven clinically, and fatigue is major side effect, just as it is for all the others. It has never been tested against the others for efficacy or side effects.

mklc profile image
mklc in reply to Tall_Allen

Thank you TA.

So all the hype about daro having no side effects etc isn't clinical fact!

Good to know.

Thank you so much.

Tall_Allen profile image
Tall_Allen in reply to mklc

This is from the Nubeqa prescribing info based on the clinical trial for its use in non-metastatic castration-resistant patients:

Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo.

Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%).

Permanent discontinuation of NUBEQA due to adverse reactions occurred in 9% of patients receiving NUBEQA. The most common adverse reactions requiring permanent discontinuation in patients who received NUBEQA included cardiac failure (0.4%), and death (0.4%).

Dosage interruptions due to adverse reactions occurred in 13% of patients treated with NUBEQA. The most common adverse reactions requiring dosage interruption in patients who received NUBEQA included hypertension (0.6%),diarrhea (0.5%), and pneumonia (0.5%).

Dosage reductions due to adverse reactions occurred in 6% of patients treated with NUBEQA. The most common adverse reactions requiring dosage reduction in patients treated with NUBEQA included fatigue (0.7%), hypertension (0.3%), and nausea (0.3%).

The most common ( vs placebo) adverse reactions, including laboratory test abnormalities, were AST increased (23% vs 14%), neutrophil count decreased (20% vs 9%), fatigue (16% vs 11%), bilirubin increased (16% vs 11%), pain in extremity (6% vs 3%), and rash (4% vs 1.4%).

Clinically relevant adverse reactions occurring in 2% or more of patients treated with NUBEQA included ischemic heart disease (4%) and heart failure (2.1%)

mklc profile image
mklc in reply to Tall_Allen

Serious points to consider. There is no free ride.

Thank you so much TA.

All best wishes

PCaWarrior profile image
PCaWarrior

urotoday.com/conference-hig...

Some men do not notice a change in ARTA. Some do. I was one who noticed a dramatic change. I am unable to use Xtandi. My MO provided me with a sample of darolutamide. After trying it I fought to receive authorization.

My advice: try it. Get a sample from your MO if you can. Then decide.

ARTA
Benkaymel profile image
Benkaymel

I can only speak from my own experience. I've been on Xtandi (enzalutamide) for 9 months in addition to Prostap (lupron). I get the expected hot flushes, fatigue and body changes from ADT but other than a bout of vertigo last December, I can't say that I've had any side effects specifically due to the Xtandi. No obvious cognitive decline so far.

I've also got lymphoedema due to radiotherapy and back pain due to bone metastases.

Good luck with your journey.

CarlosBrasil profile image
CarlosBrasil in reply to Benkaymel

It looks not so bad to me, thanks for sharing. I hope you keep doing well.

Seasid profile image
Seasid

Apalutamide and abiraterone parallel

Cancer Copilot

Thank you for your question! Apalutamide and abiraterone are two different medications that are commonly used in the treatment of prostate cancer.

Apalutamide is a medication that belongs to a class of drugs called androgen receptor inhibitors. It is used in the treatment of metastatic castration-sensitive prostate cancer, which means that the cancer has spread to other parts of the body and is still responsive to hormone therapy. Apalutamide works by blocking the action of androgens (male hormones), which can fuel the growth of prostate cancer cells.

Abiraterone, on the other hand, is a medication that belongs to a class called androgen biosynthesis inhibitors. It is used in the treatment of metastatic castration-resistant prostate cancer, which means that the cancer has spread to other parts of the body and is no longer responding to hormone therapy. Abiraterone works by blocking an enzyme called CYP17, which is involved in the production of androgens.

While both medications are used in the treatment of prostate cancer, they have different mechanisms of action and are typically used in different stages of the disease. Apalutamide is used in the earlier stages, when the cancer is still responsive to hormone therapy, while abiraterone is used in the later stages, when the cancer is no longer responding to hormone therapy.

It's important to note that the specific treatment approach for prostate cancer can vary depending on various factors, such as the stage and aggressiveness of the cancer, as well as the patient's overall health and preferences. Therefore, it's always best to consult with your healthcare provider for personalized recommendations.

Seasid profile image
Seasid in reply to Seasid

Cancer Copilot :

malecare.org/

Concerned-wife profile image
Concerned-wife in reply to Seasid

that quote seems outdated to me. It seems most men start on Abi perhaps now that it is so much less expensive than the other drugs.

Seasid profile image
Seasid in reply to Concerned-wife

Good point. I was just wondering what is better at early stage to use?

I actually agree with you. My only problem with Abi is that it goes with Prednisolone and that is something what I don't like. I am polimetastatic and therefore I can see the advantages of abiraterone. Abiraterone is a system treatment for the whole body even for the cancer in the brain while apalutamide may don't cross the blood brain barrier and therefore may don't fight brain cancer at all? I am not sure in that but that is what I believe.

Sometimes it is interesting what the pharmacist recommends. I could easily develop brain mets as I have mets in my spine and neck and apalutamide may don't fight cancer in the brain.

joeguy profile image
joeguy

I had to stop the combo of Xtandi/Firmagon due to cardiac and cognitive side effects. I have been on Orgovyx/Nubeqa for some time now with very few side effects, but that is just my experience

dhccpa profile image
dhccpa

If your MO says there's no medical evidence, what makes you feel there is? That part confused me.

CarlosBrasil profile image
CarlosBrasil in reply to dhccpa

When I read and hear that Darolutamide does not cross the brain barrier, I think it´s natural to assume that there is less cognitive effects.

Answers here seems to confirm that my MO is right, which gives me more tranquility.

dhccpa profile image
dhccpa in reply to CarlosBrasil

Got it thanks

Seasid profile image
Seasid

I also believe that the use of darolutamide is the least problematic. I would take it.

Shams_Vjean profile image
Shams_Vjean

Review, not a stand alone RCT, cited below indicates increased risks, but doesn’t really reflect a significant difference between the 2nd-line AR drugs, that I can see anyway.

I’d fight for the Daro because it been showing excellent results AND doesn’t cross the BBB, which I think could be shown as clinically significant if they ever get to doing comparative RCTs regarding cognitive decline. That’s just my hunch.

Investigators conducted a systematic review and meta-analysis of 12 randomized clinical trials published 2011-2020 involving 13,524 men with metastatic or nonmetastatic prostate cancer who were treated or not with abiraterone, apalutamide, darolutamide, or enzalutamide.

Second-generation antiandrogen users had a significant 2.1-fold increased risk of cognitive toxic effects compared with nonusers, Kevin T. Nead, MD, MPhil, MD Anderson Cancer Center, University of Texas in Houston, and colleagues reported in JAMA Oncology. They also had a significant 1.3- and 1.9-fold increased risk of fatigue and falls, respectively, including falls requiring hospitalization or invasive intervention. Older men had greater risk for fatigue. Baseline cognitive function was unknown:

renalandurologynews.com/hom...

CarlosBrasil profile image
CarlosBrasil in reply to Shams_Vjean

Thank you for the info and your view, both are useful.

j-o-h-n profile image
j-o-h-n

I've had a bad reaction to Nubeq/*/a /* = u/)..... Even since I started using it I keep trying to insert the Letter U after the letter Q. Drives me crazy......

Good Luck, Good Heath and Good Humor.

j-o-h-n Tuesday 07/11/2023 6:26 PM DST

MateoBeach profile image
MateoBeach

Darolutamide is so much better than enzalutamide in several ways including less mental side effects and fatigue and greater resistance to mutations causing failure. Take the Enza for a month or two then report possible seizures and terrible side effects. Declare that you are “allergic” to it and insist on Darolutamide. That is what I am doing to get it.

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