Zytiga vs Docetaxel in mCRPC - Advanced Prostate...

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Zytiga vs Docetaxel in mCRPC

Break60 profile image
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I just watched a video from Prostate Cancer Today which discussed the use of Docetaxel vs Zytiga in mCRPC . One take away was that with Docetaxel quality of life returns after six months of treatment whereas with Zytiga you suffer thru some three years of treatment with related side effects. Plus Zytiga is much more expensive.

The implication of course is that after six months of Docetaxel you’re not under other treatments so guality of life is ok whereas with Zytiga quality of life is poor for the entire period of treatment.

This surprised me and seemed overly simplistic. Is there really such a clear cut advantage to Docetaxel vs Zytiga??

Bob

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joancarles profile image
joancarles

I can not tell you anything about Docetaxel, so far I have not had chemo.

But I have a 13-month experience with Zytiga. The side effects, in my case, are minimal. For me the most annoying effect are hot flashes, but I have them controlled.

I ask God to give me a very long journey with Zytiga. For me he is being very comfortable.

But always remember: we are unique. Each one reacts differently.

I hope it helps.

Cynthgob profile image
Cynthgob in reply tojoancarles

How do u control them??

dlestercarlson profile image
dlestercarlson

I was being treated with Zytiga for about 16 months and have had 13 treatments using Docetaxel. After having been on both, Zytiga had less side effects for me, mainly daily fatigue. With Docetaxel I had a long list of side effects which I had to deal with every three weeks after an infusion. Both drugs worked well to control the cancer. I had a $200.00 per month co-pay with the Zytiga. Because you eventually get toxic with Doxcetaxel, I have been on a 5 month Chemo holiday. During that time my PSA has shot up from about 3 to 16, so I am scheduled to get my next Chemo treatment in about 1 week.

Drcrunch profile image
Drcrunch

I assume that there is big difference. Docetaxel kills cancer cells except stem cell where zytiga puts them into dormancy (sleep)

I've been on Zytiga for 4 months now and from my experience, there's no comparison between Zytiga and Docetaxel in terms of side effects. I think you would find that most people who've had both will agree. So far, I've had no side effects from Zytiga whatsoever. The side effects of Docetaxel were much worse, but they are limited to a shorter period of time. I'm not criticizing Docetaxel, in fact I will most likely do it again someday if it is still effective. But the side effects are significant.

Break60 profile image
Break60

I think that, because of the SEs , guys put off chemo as long as possible. The video stated clearly that using chemo early while you’re strong is better because you can better tolerate a full course. But I’m wondering if chemo is so effective that you can be off all treatments for a long time thereafter . For you gents that had chemo, were you in fact off treatments for quite awhile- like years - thereafter?

I’m interested in this issue because I’m oligometastitic and am about to use sbrt again to kill the two bone mets found recently. I went back on xgeva and trelstar but if trelstar doesn’t work I have a decision to make re: the next systemic therapy.

Thanks for your inputs.

Bob

AlanMeyer profile image
AlanMeyer

As others have said, the response to either drug, docetaxel or abiraterone/Zytiga, varies by person. I suspect that the docetaxel side effects also vary somewhat based on the specific methods of treatment and the care taken by the chemo team to manage side effects.

Remember that if side effects are unbearable you can stop a treatment and start the other one. If that is true, then I think the main question is, Which treatment is best for your cancer? In what follows I'll use the acronym "ADT" to mean androgen deprivation therapy given with one of the standard drugs - Lupron, Eligard, Zoladex, etc. By "others" I mean docetaxel (Taxotere) or abiraterone acetate + prednisone (Zytiga)

As I understand the trial results, outcomes of the treatments are different for men with high volume metastases than for men with low volume metastases. For high volumes, the combination of ADT + either one of the others is more effective than getting ADT followed by one of the others after ADT fails. However for a patient with a low volume of metastases, ADT + Zytiga still works better than ADT alone followed by later Zytiga, but ADT + Taxotere does not. It turns out to be no better than ADT alone followed by Taxotere after ADT fails. In the low volume case, early chemotherapy buys you the side effects but, if my understanding is correct, doesn't give you any countervailing benefit.

Tall_Allen has a very informative and recently updated blog entry about the big trials of the different drugs. See: pcnrv.blogspot.com/search/l...

I'm not an expert on these things, though Tall_Allen is. Please don't take my word for any of this but check with experts before making a decision.

Best of luck.

Alan

Hazard profile image
Hazard

Hi, we can all tell you how we fared with different treatments but that has little bearing on your case. We are all different and have different side effects and different responses.

I haven't had zytiga but I have had docetaxal and in my case, side effects were limited to losing most of my hair which has grown back and loss of toenails on both big toes. No nausea, no fatigue, no loss of QOL. No need to wait wait for 6 months to wait for QOL to return.

So if QOL is your concern the docetaxal iwas great for me - but not for other men. HOWEVER the big assumption that you make is that you get approx 3 years response from both. If that was definitely the case then docetaxal is a no-brainer BUT karma hit me big time. Sure I had minimal side effects but I became chemo resistant after 6 cycles. PSA fell hugely from Cycle 1 to Cycle 6 but starting rising after Cycle 7. We tried 2 more cycles but PSA continued to rise after cycles 8 and 9. So we stopped at that time. Maybe you can't get both minimal side effects and a sustained response.

So QOL is important but the efficacy of treatments varies for each individual. The big problem - you dont know whether you as an individual will get a good response until you try it. It's all a crap shoot.

BigM62 profile image
BigM62

One reason docs suggest chemo first is based on the tumor load. The more widespread, the better chemo will be to essentially bomb it and kill it. As someone else said Zytiga doesn’t bomb - it puts it to sleep. I did chemo first at 54 with widespread bone Mets. I am young and very fit and 10 rounds of chemo took me to no longer having any visible Mets and PSA undetectable. Still in Lupron. It’s been 6 months after now - average months to reoccurrence was quoted to me as 33months. But of course I hope to be an exception for more. Looking back I am very very happy with chemo first. It was hard and I did not work during. But side effects were less difficult than I expected. My main problems were constant fatigue, and constant immune system issues with low white blood cell counts. Now it’s been 6 months and I have been back at work full time for that duration. I feel exactly the same and as healthy as I did before the cancer - exception being my Lupron sweats. I will say that is also due to really really working in the gym to keep my flexibility and muscles away from Lupron!

Bedrich profile image
Bedrich

I had 6 months on Zytiga and 6 rounds on Docetaxel. Zytiga did not feel any side effects. Docetaxel was more problematic.

Patrick-Turner profile image
Patrick-Turner

My Pca became resistant to only Lucrin ADT in early 2016, after a total of 5 years of ADT. Psa was rising and I had a first PsMa scan which showed 2 upper lymph nodes as positive and fairly hot PG which had not been removed due to too much cancer out of capsule and Gleason 9+9 in late 2009.

I'd had EBRT in 2010 and in 2016 I had extra salvation IMRT to PG and was first in Oz to have this. But I had Cosadex begin on day of this IMRT beginning, and I got another 6 mths of Psa suppression due to blocking action to testosterone.

But this all failed by early 2017 so I began Zytiga plus the ADT and this gave 8 months of Psa supression.

But before starting Zytiga, I had a double TKR in Feb 2017 while Psa < 1.0, and I recovered well and re-joined a cycle group Ihad not cycled with for 4 years and surprised them all by riding faster than anyone else my age, and faster than the

women of all ages who turned up for the typical 85km rides. But by October, I began getting symptoms of bad heart rate stability and I found it impossible to ride when temp went over 25C on warm days of spring, so I quit the group.

In early 2018, the Psa began to go up as Zytiga failed, and I began Docetaxel in July, and had 5 infusions over 15 weeks. Psa went from 12 to 45, and showed the chemo was a failure. But for first 3 chemo cycles, The side effects of Zytiga persisted but they were nowhere near as bad as the side effects of chemo with neuropathy being the worst. Leg muscles hurt, and I cycled slow, but by 4th chemo I had learned to recover for the next chemo by always cycling at least 20km in everyu day of cycle. I was able to cycle 19km to hospital to get chemo, then ride 19km home, and I felt fine until the gloomy 5 days after the chemo day.

It seems to me that ADT and Cosadex and Zytiga and Enzalutamide are products which lead to sweeping the cancer under thr carpet, or in other words, the can gets kicked down the road, because these products do not seem to kill any Pca but just slow down their speed of growth. Chem does kill, but it is in your body for only a short time so cancer is killed forthat time, and after than the cancer grows, so the Psa does not go down, it kind of settles to a level where 2 steps forward equal 2 steps backward.

I quit the Docetaxel after 5 infusions and a month after the 5th I had my first infusion of Lu177, and i'll have another before Xmas, and if my Psa is lowered I will be happy. I have had a total of 4 x PsMa scans since the first in May 2016.

All have showed steady slow progression of my cancer.

But I have not had another that might indicate some good came from chemo, and its all irrelevant history now because the only thing that matters is the future.

The week since first Lu177 gave me slight nausea and I now began pills to control it and I did have continuing neuropathy in legs and I had leg swelling with fluid so I have used tight stockings for last 4 days and today the swelling seemed less, and so the combined side effects of chemo plus those immediately after Lu77 inject are not as bad as chemo alone, and I had a good cycle ride today.

I am thinking now it would have been better to have begun Lu177 before chemo began, but Psa was only 12, and I felt I could at least try the darn stuff and it would not make much difference even if Psa went to 50. Many having Lu177 have Psa 500 at start, and then there is a lot of work for the Lu177 to do, and its more difficult to halt the Pca when there is a lot of it in bones. My Lu177 doc said I did not come to Lu177 too early, and a trend in Germany where Lu177 was first used is that men come early rather than too late as confidence grows about this Theranostic treatment.

I have no clue if Lu177 is working, but my doc said that is I get bone pain, take the predisolone tablets, maybe 4 a day, to ease the pain, and so far, not much pain, but there is some where I know the Pca has invaded my bones, in my cervical bones especially. So far I have not taken any prednisolone.

Now why have any of this stuff? Well, it was necessary with Zytiga because the adrenal glands are shut down or mucked about with so the cortisol hormones it makes is stopped, so the predi pills just replace what you'd make naturally.

But now I am not on Zytiga, would not my adrenal gland have returned to normal? I guess so. AND it would now be making a small amount of testosterone which feeds my Pca. The continued ADT with monthly Lucrin continue, so balls are turned right off. If I did not continue Lucrin, it is possible my balls would not turn back on and start making a large amount of testosterone - long term chemical castration tends to stuff up one's balls for good.

But testosterone is still my enemy. The long period of supression with ADT has probably helped my cancer to mutate to make its own di-hydro-testosterone.

One might say that when an RP fails, or EBRT fails, don't use ADT, just go straight to Lu177. I don't know anyone who has done this, but then doctors don't like the idea because there's only one main cancer site, the PG, and the hundreds of mets that have formed before diagnosis are still so small no PsMa scans can see them and no Lu177 wouldf find its way to them so they'd all grow until they reach a size able to worth cropping.

The answer to Pca cure is probably with immune therapy that is a long way from becoming wide spread mainstream treatment. Success rates are still very low, and although Provenge looked good at first, it only gave median of 4 mths life extension; BUT, a few guys got 9 years, they were among first to be treated and their white cell alterations are being reproduced in new generations of white cells which continue to recognise their Pca as ememy cells, not friends.

I have 3 enemies, aging, the side effects of treatments, and the effects of the disease itself, and the latter has yet to really affect me except frighten me.

So I think Pca will kill me, so I know the certainty is death, but not when, and the other certainties are taxes and doctors' bills.

It was beautiful spring day here for my cycle ride, and I typed to several ppl online, and doc was pleasant with Lucin inject, and I got some work done on website and in workshop on craft work. Life is still good right now.......

Patrick Turner.

Break60 profile image
Break60 in reply toPatrick-Turner

Thanks for all your comments.

I’ve been “lucky” in the sense that I’ve had very low volume : Never more than two visible mets at a time which is why I’ve used radiation and “just “ ADT3 for each recurrence.

And since I’ve used state of the art imaging ( this time PSMA ga68) I’ve found these mets early on compared to standard bone scans or mri .

Patrick-Turner profile image
Patrick-Turner in reply toBreak60

Indeed the PsMa Ga68 scans are good, but in my case the 4 I have had have failed to show countless tiny mets that were always going to cause me to seek systemic treatments in favour of any further local treatments.

IMHO, no man should ever assume the mets count is low when in fact there may be hundreds of tiny mets which are all going to grow larger to determine overall survival. The mets that seeded themselves around the body are often suppressed by ADT with the main primary tumour at PG but when ADT fails, it is because of tumor mutations that occur in many places and this process is far from fully understood, or countered fully by medical procedures. Its why about 30% of men diagnosed with Pca will die from it. Men like to think they have their Pca under control, and that there is not much cancer present, but in fact there may be many more mets than they ever thought possible.

Even with Lu177, I can suggest that if the met size is very small, and it is PsMa avid, it may not attract any Lu177 molecules to anchor themselves near the met site so the tiny met is not radiated. The larger mets attact enough Lu177 to cause cancer cell death providing conditions and cancer cell properties make it likely. But not in every met case. There are always survivors of radiation, and they can be untreatable if they grow large and mutate to resist any treatments. There can be a time when the medical treatments are in vain because side effects wreck the man, who is also aging faster than normal due to effects of Pca and side effects. I am not at this point, but I may well be in future.

Patrick Turner.

Break60 profile image
Break60 in reply toPatrick-Turner

Neither the PSMA scan nor any other can “see” micro mets. For this reason , I’ve employed sbrt to bone mets visualized and Systemic therapy to invisible micro mets. I may be wrong but I believe killing mets imaged by highly sensitive radiotracers with sbrt prolongs life and using systemic therapy on the little guys keeps them from growing or slows them down before they grow into killers. The issue is which systemic therapy to employ.

Bob

Patrick-Turner profile image
Patrick-Turner in reply toBreak60

I am far from being an expert in SBRT but I did have some in 2016 to give additional salvation 31Grey to my Pg which had only 70Gy inn 2010, and not enough to kill Pca with inoperable Gleason 9+9.

There were side effects of the "pencil beam" SBRT'' given to 2 lymph mets each side of my oesophagus. I am now having trouble with reflux and nausea because such pencil beams to small mets difuse into wider beams which affect all things they pass through and they are not really pencil beams at all, IMHO.

But in 2016, there were only 2 mets on PsMa scan, but during next 2 years there were countless mets on PsMa scan. Nobody could have all of them zapped with SBRT. It seems to me my only option was systemic therapy where a small met is likely to get about the same zap from chemo or Theranostic with Lu177 as a larger met, but I cannot be sure about any of this, and I've never seen any detailed discussions and scans to track what the Lu177 really did, or where it actually went.

The docs tell me the Lu177 is likely to go wherever PsMa avidity exists. But IMHO, there may be a threshold for met size below which no Lu177 is held to any very small met by the ligand. So the tiny mets just grow and grow, and so when they get big enough, you have more Lu177 to get them. I know guys who have had many Lu177 infusions. Some have only 2, and if Psa goes low enough, they don't need the other 2 infusions to make up 4 infusions for what is a standard course of treatment. But often the soft tissue mets seem to vanish with 2 infusions, and bones might need the 4 infusions or more. and dose size and timing is worked out by doc because he must know how the hundreds of other patients have fared for last few years he has operated here in Australia. What I am buying is extended QOL before the bone mets or any other mets have grown big enough to attack any internal organs or cause micro fractures in bones.

I may make very little difference to overall survival time because Pca has a nasty habit of mutating and not being Psma avid, so Lu177 can become uselsss, and then chemo fails again, and I end up with runaway Pca that nothing can kill, plus lots of side effects, and I'll be older. Radium 223 then

becomes an option, but side effects can be severe......

But today I rode 30km, very nice, but reflux and nausea were a slight problem, so I have to eat less, and take pills for both reflux and nausea.

Its difficult for me to say whether the Lu177 infusion has exacerbated the damage done by 5 chemo infusions. There are too many variables now, nothing is certain any more. But the swelling in lower legs has subsided, and I am happy to not have it continue. Some men are in a wheel chair due to neuropathy effects and swelling of legs after chemo, with great reduction of QOL.

Patrick Turner.

FCoffey profile image
FCoffey

QOL of life in an important part of the risk balance, one that is too often ignored. It's good to see a thoughtful attempt at balancing QOL effects between 2 different treatment options. As many have noted, we are all different and will respond to each drug differently, but that doesn't mean you can't evaluate QOL in your decisions about ongoing treatments.

But it is vital to always look at all sides of the risk balance. Does one treatment work better than the other to control the cancer, extend life, reduce or eliminate symptoms?

For men with organ-confined disease the answers are fairly well known, even with the wide variations between individuals. Those men are usually offered the choice of active surveillance AS), radiation therapy (RT), or radical prostatectomy (RP). The PROTECT trial, a large, randomized, long-term study assigned men to each of these treatments.

nejm.org/doi/full/10.1056/N...

After 10 years, there was no significant difference in overall mortality (death from any cause) and cancer-specific mortality (dying from prostate cancer). No difference. By that measure both RP and RT are not effective treatments.

If you change the definition of success from "will I live 10 years?" to "Will the cancer spread (metastasize or progress outside the capsule of the prostate after 10 years) the answers are nearly the same. Using AS as the control - it doesn't directly change that outcome - the effectiveness of both RP and RT is quite low. You have to give 33 men RT to prevent metastases in one man. You have to cut out the prostate of 27 men to prevent metasases in one. In other words, there is only a 3% to 4% chance that you will be that one man who gets this benefit.

The study found that 9 men would need to be treated with RP or RT to prevent progression in one man. About 11% chance that you are that man.

So the efficacy of any of the offered treatments is rather low.

The one big difference found in the study was QOL. The men on AS had much higher QOL than either RT or RP groups. All groups showed some decline, as this is a disease of old men, but there was a very obvious and statistically significant difference.

So for those men, the risk balance is clear benefit to QOL for AS, versus tiny benefits in efficacy from RT or RP, no benefit at all in terms of living or dying. Where to strike that balance is an intensely personal decision that each man must make. There is no right or wrong answer.

As for Zytiga versus Docetaxel, it will probably be a long time, if ever, before we get a study of the magnitude, duration, and statistical power of the PROTECT trial. But unlike RP and RT, you can stop treatment with either drug.

So both the QOL effects and the efficacy of each treatment have to be assessed personally, as they always do. The main difference between those of us with advanced disease and the men who can rely on PROTECT is they have some good quality data that we lack. But the fundamental challenge of making the best decision is the same.

leo2634 profile image
leo2634

I've been on Zytiga for going on 10 months now and other than E. D. My side effects are gone. I relied on my Doctors decision to start with Zytiga and I'm for th most part the same person I was before. I have a loving wife of 44 years and a supportive family to help in this devastating journey. I thank God everyday for another day and will listen to my Doctor for his advice and compassion. Never give up never surrender. Leo

Jim_S_Boston profile image
Jim_S_Boston

Jevtana following Taxotere

I had 8 rounds of docataxel, from April to Sept 2014, which was effective at knocking down the disease but with accompanying neuropathy (feet particularly) that lingers to today. Since then I’ve been put first on aberiterone and then enzalutamide until each began to fail. I also had the full round of Ra-122 injections last year for bony mets. So today quarterly MRIs show bone mets are dormant but PSA has begun doubling monthly and has gone from below 0.1 after chemo to about 1.2 now. Onc says rechallenging with docataxel will probably not be effective a 2nd time and thinks cabazitaxel (Jevtana) may be the best choice going forward.

Has anyone gone this route of Jevtana following Taxotere? Curious to know your experience. I am less ‘fit’ for the stress of chemo today than I was in 2014 and I’m wondering how well I might tolerate it.

Any input appreciated, Jim

Mkeman profile image
Mkeman

I have been on Zytiga since January...PSA is undetectable...and my quality of life is pretty good....

BartonKen profile image
BartonKen

I concur with your comments. Given the choices I read up a lot about both, including those of fellow travellers on this site ( for which I’m ever grateful having found it). The commentaries were overwhelming, kill the cells. My sixth and last Docetaxel was Sept 12, 2018. Hot Flashes, 80% loss of hair, neuropathy in the soles of my feet and weight loss (which was welcome), were my side effects up to #4 chemo. I had radiation on upper left pelvic area. Following #4 Constipation became, which led to a prolapsed hemmerhoid. This was resolved through a daily glass of Restorelax in 6 Oz of water plus a small glass of prune (cheaper to buy the prunes and apple juice and make your own). The main side effect showed up 21 days after Chemo #6 with pain in the SI joint area, followed by pain in the left groin area. Walking withstick has become awkward. I’m scheduled for a full body Neuclid scan, followed by a Ctscan to tatto the pain areas, then radiation to kill the cancer cells in those areas. I’m looking forward to becoming pain free by this month end.

joekaty profile image
joekaty

To all above comments I would add that docetaxel - even when (as with my husband) is tolerated very well is still scary to be on. Any hint of fever or exposure to illness is terrifying. Flu season was horrendous and despite whole family getting flu shots and him essentially staying quarantined during flu season- he did get the flu and end up hospitalized. It is so hard on your body with such a low white count. However, would do again in a heartbeat as his response was so excellent. He was very, very ill at diagnosis and docetaxel literally saved his life. Cancer has spread to his bone marrow and he would not stop bleeding, was in ICU, received first bag of docetaxel in between blood transfusions and it worked. Now he’s on Xtandi and does have fatigue as a side effect but much less scary than being on docetaxel.

I can not speak to Zytiga or any of the silver bullets developed over the last 14 years as I had no need of them. Each remain in an a4nsensl should I ever need them. Intrigued by the comment that one eventually gets toxic with Taxotere...... please explain what you mean. Oh it’s poison alright, but ....

My experience was as soon as mets were found..... 180 days which had me taking nine infusions of Taxotere alternated with nine infusions of Adriamycin plus Luoron/Eligard injections. With the infusions alternated Ketoconzale and Estramustine; plus Prednisone each day of the 180.

GD

Raymonda100 profile image
Raymonda100

Based on the research I read and what my MO told us, Lupron + Zytiga and Lupron + Docetaxel had equivalent results. If you have to be on Lupron, you will have side effects that Zytiga will likely exacerbate. But the side effects of Docataxel are very different.

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