Zytiga & Low Fat Breakfast

[LifeQuality]

Starting Zytiga tomorrow, and MO wants me to try the "low fat breakfast" regimen. Trouble is, there don't appear to be guidelines for what constitutes a "low fat breakfast" -- I read the original study and they didn't control for that. Are there guidelines any of you have found/recommend, like grams of fat or # of calories to aim for? Thanks~~

[Tall_Allen]

If the problem is that you can't afford full dose Zytiga, tell your MO to write the prescription for generic abiraterone. That is the ONLY valid reason to take a lower dose with meals and risk under or over-dosing.

[leebeth in reply to Tall_Allen]

My brother started Zytiga a month ago, and had to stop after 2 weeks due to SE. Several years ago, he was in a trial with combo abiraterone and enzalutamide, and had to discontinue both drugs due to SE. Pain, fatigue, etc. He has been on Lupron for 12 years and tolerates it well. His testosterone is <7 right now but he feels great, so I don’t think it is the testosterone lowering causing him to not tolerate.

Would one of the newer second generation drugs be better tolerated? We will need to make a treatment decision on June 22.

[leebeth in reply to leebeth]

His PSA is 4.6. Axumin PET shows small mets 6th rib. That’s all. He is 80 but otherwise healthy and independent.

[Tall_Allen in reply to leebeth]

The only one he hasn't tried is Nubeqa (darolutamide). It is so far only indicated for non-metastatic castration-resistant men, but his medical oncologist may be able to convince his insurance to cover it. It may be less fatiguing than some of the others. Docetaxel may be a better choice - 15 weeks and it's done.

[leebeth in reply to Tall_Allen]

Thank you. Based on my husband’s great response to docetaxiel, I agree. Now to convince my brother.

[Canoehead in reply to Tall_Allen]

I beg to differ. The original Zytiga studies did not optimize the dosage, but rather selected an arbitrary amount, which turned out to have high efficacy. Taking any meds on an empty stomach will tend to reduce total absorption. Subsequent studies suggest that lower dosages, with food, are also effective, presumably because of increased absorption.

The usefulness of the lower dosage is certainly a cost saver, but equally important, many of us have livers that don’t tolerate the 1000 mg. Daily dose of Zytiga well, so the lower dose with food is critically important to them.

[Tall_Allen in reply to Canoehead]

That's incorrect. The Phase 1 study of abiraterone was a dose-finding study, which is how they came up with 1000 mg. It is described below, FYI:

clinicaltrials.gov/ct2/show...

You are also incorrect in believing that lower doses with food are easier on the liver. If the amount of abiraterone absorbed is the same, the side effects are the same. It's not "presumably because" of increased absorption, that was definitely found to be true. However, the amount of absorption with food will vary across individuals - to be sure you are getting the right amount absorbed, take 1000 mg without food. Only take it with food if you have to save money (less important now that lower cost generics are available).

[Canoehead in reply to Tall_Allen]

I’m no scientist, but I can read. The Phase 1 study of Zytiga had 27 members, and the link you posted suggests that the purpose was to find the maximum safe dose, not the optimum dose (although maximum might equate to optimum in the manufacturer’s mind).

From the study description: “On receiving notification of the confirmation of safety of 500 mg of the drug, patients of cohort 1 who are currently on continuous administration can receive increment 500 mg per day starting from the next cycle (If the dose escalation would not be appropriate due to safety reasons, the patients will continue the original dose). Furthermore, on receiving notification of the confirmation of safety of 1000 mg, patients of previous cohorts who are currently on continuous administration can receive increment 1000 mg per day as well from the next cycles (If the dose escalation would not be appropriate due to safety reasons, the patients will continue the original dose). JNJ-212082 will be orally administered once per day. “

My impression is that the manufacturer’s (Janssen’s) working hypothesis for Phase 1 was that if a little is good, more must be better. I’ll stand by my statement that an “‘optimum” dose has never been established, although 4 pills per day rather than one or two certainly is optimum for Janssen.

[Tall_Allen in reply to Canoehead]

That's the way ALL dose-finding studies are done. It is based on the fact that for almost all medication there is a "dose effect" meaning that effectiveness increases with dose. The dose effect almost always follows an S-shaped curve - after a certain point, the effect of adding more drug has diminishing returns. Dose finding (Phase 1) studies try to balance increased dose with toxicity. That's how the dose on all the FDA-approved drugs you may take were determined. "Optimum" means the balance of efficacy and safety, so it was certainly determined for abiraterone in spite of your erroneous beliefs.

[Hidden in reply to Canoehead]

I'm equally puzzled how TA cannot see there is more than one way to achieve benefit from Zytiga. Of course the manufacturer wants to discourage people from taking a lower dose. Pharm companies are not altruistic-- they are profit driven.

Oncologists are now recommending the lower dose with food and it has been considered SOC since at least 2019 when NCCN Guidelines published this:

"A randomized phase 2 noninferiority study of 75 patients with M1 CRPC compared 1,000 mg/day abiraterone with prednisone after an overnight fast with 250 mg/day after a low-fat breakfast. The primary endpoint was log change in PSA, with secondary endpoints of PSA response (≥ 50%) and PFS. The primary endpoint favored the low-dose arm (log change in PSA, −1.59 vs −1.19), as did the PSA response rate (58% vs 50%), with an equal PFS of 9 months in both arms. Noninferiority of the low dose was established according to the predefined criteria. Therefore, abiraterone with prednisone can be given at 250 mg/day administered after a low-fat breakfast, as an alternative to the dose of 1,000 mg/day after an overnight fast. The cost saving may reduce financial toxicity and improve compliance. Food impacts absorption unpredictably; side effects should be monitored and standard dosing (1,000 mg on empty stomach) used if excess toxicity is observed on modified dosing (250 mg with food)."

TA's assumption that each person absorbs the same amount of the drug when they take 1000 mg on an empty stomach (vs 250mg with food) makes no sense. A person weighing 150 pounds vs one that weighs 300 will absorb different amounts as will a person with, say, a compromised liver. Add the variances of 5 mg of prednisone or 10 mg of prednisone (or none in some cases) and I'd be surprised if anyone got the same dose!

Also, with T-NEPC (treatment emergent neuroendocrine PC) now affecting up to 30% of castrate resistant men, it makes sense to take a lower dose if it works. There are no studies to my knowledge that break down dosages and T-NEPC emergence but that has to be something doctors are discussing. Tall Allen's blanket statement that the only acceptable dosage is 1000mg unless cost is an issue is absurd.

[LifeQuality in reply to Hidden]

THANK YOU so much for your detailed response. I am so thankful for ALL the responses to my question, and the healthy "debate"/discussion that it initiated. Your response, as well as strummer's, were esp. useful. Cost is not an issue, as my health plan only charges me $20/month for Zytiga. I'm more concerned with SEs, and my MO says that her patients doing the "with food" regimen report less nausea than her patients who take on an empty stomach. Also, eating a low-fat breakfast is my routine, vs. having to wait to eat. Interestingly, she still prescribes the "empty stomach" regimen to her patients that aren't very disciplined about their diet. THANKS AGAIN!

[Jeremiad53 in reply to Canoehead]

Yours is a 3 year old reply, I am currently doing the low dose, and struggling to find something I like The 1,000 mg on an empty stomach led me to constant constipation, With the low dose and1 cup lowfat yogurt and banana plus cereal works, but it makes me hungry all day. I would like a high protein, low carb meal that is low in fat to satisfy my hunger for the day.

[strummer]

my husband started this dosage a few weeks ago. it wasn't a cost issue, but if possible he wants to take fewer pills if it doesn't compromise the effectiveness. we doubled checked with his 2 prostate oncologists and this regime is now included as a standard of care option. his faves- poached egg, toast, yogurt, cereal, fruit, breakfast bar (any combos).

he aims for no more than 10 g fat and 300 calories. hope you do well!

[spencoid2 in reply to strummer]

I know it is difficult to get any idea how effective the lower dose it. I believe they are doing more trials on this. I have heard mixed opinions on the Indian study and maybe others. I would very much like to try the lower dose if possible. So keep us informed and if there are any other opinions on this? I believe that the side effects of taking abiraterone are virtually all due to the lack of testosterone so whether you take one or four probably has little effect. If this is not the case and there are effects from the quantity of drug i would definitely like to do the lower dose. Ideally I could continue the same script and give the excess to others who do not have insurance. My MO suggested keeping on the four pills but i will ask others. Maybe Dr Aggerwall will have an opinion when i have my phone appointment on Monday.

Of course i will get a better idea on Monday. Hopefully there will be a phase three study for 177Lu-PSMA-617 for castrate sensitive patients. It seems that 177Lu-PSMA-617 may be more effective if started earlier.

Any other ways of gaming the system? Also i asked before but don't think anyone answered. I am not sure but think that in phase three studies, everyone gets the drug? If either this is not true or if i get on a phase two study, is it seriously unethical to quit the study if i find i am on placebo? I plan to check my radiation level and if it is not elevated it would mean i am on the placebo. I believe there is the option to get the "juice" after the end of the study but that is 6 months later and the goal is to do this as soon as possible.

[MateoBeach in reply to spencoid2]

Your post is very interesting so I will chime in and hope T_A doesn’t send me up I’m flames 🔥 😆. First, a trial and approval for Lu PSMA on HSPC is just not going to happen soon enough. Too expensive and have to wait too long to determine median survival, is my guess. This may come after it is widely adapted for mCRPC and centers do smaller trials to explore it. (And of course it will work as well and probably better in HS setting. We already know that from trials overseas.)

So if we want it without waiting for CR we have to go abroad and pay for it. As many have done.

As far as a way to “game” determining adequate abiraterone dosage: Abiraterone powerfully inhibits androgen synthesis and can produce a measurably castrate testosterone level WITHOUT added ADT drugs. So if you took it as mono therapy, I propose that if a dose reduction kept T levels equally low and fully castrate, then that could be a surrogate measure of efficacy of the dose. (Absent actually measuring peak and trough serum levels of the drug.)

[spw1 in reply to MateoBeach]

re arbiraterone without added ADT, my husband's MO says that if we were to use abiraterone, he would definitely want to continue with LHRH therapy since the enzymatic blockade alone would not be sufficient to exert appropriate androgen suppression. Do you have anything I can send him about using arbiraterone without ADT? We are now watching post-SBRT and no PSA testing will be done for a few more weeks and no decision on any further treatment until that point. But I would like to know if ADT is necessary or not with arbiraterone or enzalutamide esp since some of the doctors on the team say that there is resistance to ADT.

[MateoBeach in reply to spw1]

It is not proven in trials which all use concomitant ADT as the SOC. But o do know that some individuals have tried it without and found it produces castrate T levels alone. The only way to know is to try it and measure the T level. If it is castrate or even lower then there is nothing additional to be gained by also adding ADT drugs. The only thing they do is lower testosterone by inhibiting testicularProduction which abiraterone can do on it’s own. Don’t expect most docs to consider Simply trying it.

[spw1 in reply to MateoBeach]

Thank you.

[Tall_Allen in reply to strummer]

It's still 4 pills, but the micronized version of abiraterone, Yonsa, is at least smaller pills and you don't have to worry about taking it while fasting.

[Lettuce231]

I've been having a good breakfast of fried egg on toast, yoghurt and mugs of tea for years, I take the prednisone about an hour before, then 500 mg of Zytiga with breakfast.

I did it to minimelise the long term side effects, it's worked well for me, I didn't over complicate things by trying to calculate calories etc.

I think that it will 4 years in September, my PSA is now below 0.04.

Phil

[Tall_Allen in reply to Lettuce231]

If you are absorbing the right amount of abiraterone, the side effects will be no different. If you are experiencing fewer side effects, you are probably absorbing an inadequate dose and getting less benefit from the medication.

[Lettuce231 in reply to Tall_Allen]

Thanks T.A.

I still get the " normal " everyday side effects with the treatment, I find the Lupron jab is the worst, especially if it administered too quickly, I now have that, every 3 months.

My main concern was the overall effect on my body, everyone of the drugs that we have to take, has a kick back.

But I do take your point, don't worry T.A. I'm still suffering

🤣🤣.

Phil

[Tall_Allen in reply to Lettuce231]

If your main concern is the overall effect on your body, you gain nothing by taking a lower dose with food. The amount absorbed is the same, hopefully.

[Hidden in reply to Lettuce231]

That is good! 👏🏼👏🏼

[Lettuce231 in reply to Hidden]

Thanks Scott 👍

[Hidden in reply to Lettuce231]

Keep rolling ✌️

[mrscruffy]

I est loots of protein and lift weights 5 days a week. Seems to help with the SE's. It is also effective in fighting weight gain, I never eat potato products and if I try my wife nd friends stop me, even my friends kids stop me(talk about support). If weight goes up I have found great success with intermittent fasting, just lost 14lbs in six weeks before my trip to Costa Rica. During the last two years of this my PSA has been sub 1.0. This is just what works for me Hope this is of some help to you.

[Hidden in reply to mrscruffy]

Viva Costa Rica .

[rmarkley]

I have been on the 250 mg abi since Aug 2020, along with Firmagon. Firmagon started in July 2020. My breakfast is either oatmeal, a handful of raisins, tea and fruit juice during the week, or a couple of eggs with 2 slices of toast, tea and juice on weekends, PSA is unmeasurable, ands T is <7. The 250 mg abi with low fat breakfast is not a myth, it works. I don't know what a high fat breakfast would be- a pile of bacon, thickly buttered toast, scones with heavy cream over them, big pile of fried potatoes? Certainly nothing that anyone with Pca should be eating anyway.

[MateoBeach in reply to rmarkley]

True. But if it were my dying last breakfast, sounds rather fun. 😛🍳🥓🧇🥐

[spencoid2 in reply to MateoBeach]

I prefer creme fresh on my scones.

[MateoBeach in reply to spencoid2]

👍👍

[carbide]

What does SE stand for?Standard Error?

[leebeth in reply to carbide]

Side effects

[carbide in reply to leebeth]

Da'...So many abbreviations, acronyms.

Thx.

[wat380bjw in reply to carbide]

Side effects

[Pheart2]

I’m taking 250 mg with low fat breakfast (defines as no more than 3 gram of fat for 100 calories) since one year. PSA undetectable. This is based on a small study done a few years ago.

[spencoid2 in reply to Pheart2]

so is it generally agreed that 250 with 300 cal low fat diet might be just as effective? the only reason (if the side effects are the same) to do the lower dose would be to be able to share the rest. i am probably willing to try this if there is anyone who does not have insurance to cover abiraterone.

[Jbooml]

So I might as well chime in...I completely defied my MO’s advice to take the Z on an empty gullet from the getgo . It just frightened me to ingest that quantity..but so did the alternative of overdosing while taking it with an indefinite caloric control...I settled on 500mg along with a banana and creamed coffee. It’s working. No SE’s and I’ve maintained biological remission levels throughout.Just my humble survival experience.