Xgeva dosage regimen?: The standard... - Advanced Prostate...

Advanced Prostate Cancer
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Xgeva dosage regimen?

HopingForTheBest1
HopingForTheBest1
51 Replies

The standard approved dosage regimen for Xgeva is having an injection every 4 weeks. My Oncologist has been concerned about potential toxic side effects of this drug, such as necrosis of the jaw. As such, he has been treating me less frequently at 6 week intervals. I have been on this drug for several months, as I have metastasis to the pelvic bone.

Is anyone else taking Xgeva on a other than a 4 week treatment cycle?

Has anyone experienced side effects from Xgeva, and was it significant enough that you had to stop taking it?

51 Replies
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Lagovista2018

My husband is on Xgeva has been taking it since mid September of this year. He had the shot while on chemo back in February and it drained all of his calcium that it put him in the hospital for a few days so he can get calcium treatment. So his oncologist wanted to wait to give him the Xgeva shot once his numbers were back up. She also wanted him to take calcium pills daily to help. She did mention that he could get nercrosis of the jaw but to check with his dentist regularly. He has to get the Xgeva shot once a month so far the only side affects he’s gotten is some light headaches

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Tall_Allen

Yesterday, Fred Saad presented his findings that it is not a good idea to give Xgeva or Zometa less often. He recommends taking the full dose at recommended frequency for at least 2 years and re-assessing then:

urotoday.com/video-lectures...

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HopingForTheBest1

Thanks. I did see that video interview, and will discuss with my Oncologist shortly.

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Tall_Allen

And you might as well take Celebrex with it. It was tested with Zometa, but maybe it synergizes with Xgeva too.

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tango65
tango65
in reply to Tall_Allen

The mechanism of action of Zometa and Xgeva are completely different. There are not data to support that adding Celebrex to Denosumab ( Prolia, Xgeva) could offer any benefit to a patient.

Celebrex is not a totally innocuous drug. It could be associated with cardiovascular, GI and renal problems.

rxlist.com/celebrex-drug.htm

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Tall_Allen
Tall_Allen
in reply to tango65

They are "completely different" only in the way they achieve what they do, but they are very similar in their net effect - they are both osteoclast inhibitors, and decrease bone resorption. I cannot guarantee that Xgeva increases survival by 22% when added to Celebrex the way Zometa does, but it is a reasonable hypothesis.

Celebrex has much the same side effect profile as every other NSAID (like naproxen or ibuprofen). However, it has much milder GI effects, so it can be used much longer than other NSAIDs. It was developed for people with arthritis who take it every day for many years as a safer alternative. It has been used since 2004 in people who take it every day. I think it is worth those risks for a 22% survival increase, but everyone must decide for himself.

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tango65
tango65
in reply to Tall_Allen

I think it is worth those risks for a 22% survival increase, but everyone must decide for himself."

There is not evidence anywhere of a 22% survival increase of denosumab (Xgeva,. Prolia) plus celebrex..

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Tall_Allen
Tall_Allen
in reply to tango65

As I said, the evidence is for Zometa, but since Celebrex is usually very safe, there is not much risk in trying it with Xgeva too.

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tango65
tango65
in reply to Tall_Allen

The risk of cardiovascular complications with Celebrex could be around 3%.

nejm.org/doi/pdf/10.1056/NE...

It could be higher when patients are old and have hypertension, or diabetes, or renal and/or coronary complications.

There are not data showing a benefit in the control of the cancer by adding Celebrex to denosumab..

IMHO it is not adequate to recommend adding a drug which could cause cardiovascular/renal complications without any evidence that it could have a benefit to the patient.. Remember: " Primum non nocere:. "First do no harm" .

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Tall_Allen
Tall_Allen
in reply to tango65

The point is that the cardiovascular complication rate is actually lower than other NSAIDs. The PRECISION trial that looked into Celebrex vs other NSAIDs found:

"Compared with celecoxib, ibuprofen had more major adverse cardiovascular events (p < 0.05), and both ibuprofen and naproxen had more gastrointestinal (p < 0.001) and renal (p < 0.05) events." (2018)

onlinejacc.org/content/71/1...

So the cardiac risk of Celebrex is lower than the cardiac risk of alternatives like ibuprofen or naproxen. And the GI and renal risk is lower, which is why it has been safely used by millions of arthritic people since 2004.

I agree that when STAMPEDE looked into this, only Zometa was available for testing. So the results may not apply to Xgeva, which is also an osteoclast inhibitor. [Just as Zytiga and Xtandi have similar survival benefit, although they have differing modes of inhibiting the androgen receptor]. But it is a reasonable bet that it does apply.

So, if you want to forgo a chance at a 22% survival increase by simply taking it with a known safe drug, that is certainly your prerogative. I doubt most men would agree with you, however.

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tango65
tango65
in reply to Tall_Allen

There is not 22% survival increase, except in your thinking. You could repeat it many times, but it does not make it true.

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Tall_Allen
Tall_Allen
in reply to tango65

LOL!! - do you actually imagine I made that number up? I never make up stuff - this is about people's lives.. You can read it for yourself:

"Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 (95% CI, 0.62 to 0.98; P = .033) for Standard of Care + Zoledronic Acid + Celecoxib"

ascopubs.org/doi/full/10.12...

To translate for you, a hazard ratio of 0.78 means survival increased by 22%, which was statistically significant.

I suggest you show it to your oncologist and ask him to explain it to you.

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tango65
tango65
in reply to Tall_Allen

Your insulting explanation, does not have anything to do with denosumab (Prolia or Xgeva) and celebrex. There are not data that adding Celebrex to Denosumab offers any advantage.

Yes, you are making those numbers up when you recommend to add Celebrex to denosumb.

I do not need you to translate anything to me, thanks for the offer.

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Tall_Allen
Tall_Allen
in reply to tango65

It wasn't insulting- it was explaining something to someone who apparently doesn't know what the facts are. As I said from the very start - it may be different. (Just as it was possible that Zytiga and Xtandi might have had different effectiveness until the data showed they had similar effect.) But since the two drugs are similar in effect and Celebrex is relatively safe, why would anyone forgo the reasonable possibility of a 22% increase in surrvival? I hope you understand the point by now.

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j-o-h-n
j-o-h-n
in reply to tango65

May I have the next dance with you....... Don don don da... darada don don da

I'm 6' 1" tall, if I'm taller than you, then it's customary that I lead.....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 10/24/2019 5:31 PM DST

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GP24

Here is a video from the same conference Fred Saad was at. Chris Parker, PI of the STAMPEDE trial, is against routine use of bone health agents:

urotoday.com/video-lectures...

Frankly, after seeing images of a necrosis of the jaw I will never use these agents. This is my personal decision.

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Tall_Allen
Tall_Allen
in reply to GP24

Thanks for showing that presentation. There is clearly still a lot to learn. Meanwhile, what I believe is this:

(1) there is no need for any bone strengthening agent for most men starting ADT, and if they continue to do do weight bearing exercise at the gym, there may never be any need for it.

(2) Bone strengthening agents should only be given when DEXA scans show there is osteoporosis. Similarly, bloodwork should drive calcium and Vitamin D supplementation.

(3) If there is osteopenia, increasing weight-bearing exercise may be sufficient.

(4) Estrogen patches may be enough to reverse osteoporosis. They also may be a good alternative ADT. And they mitigate hot flashes. We will get more clarity on the risks and benefits from the trials in the UK.

(5) Multiple therapies that include second-line hormonals, and systemic radiopharmaceuticals (Ra 223, Lu-177, etc.) may dictate more frequent DEXA scans.

(6) Jaw bone necrosis is a minor side effect, but increases with time on the drug - so Dr Saad's recommendation of max 2 years seems prudent.

(7) If one is taking Zometa anyway, take it with Celebrex (with safety monitoring).

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GP24
GP24
in reply to Tall_Allen

I fully agree, except for me necrosis of the jaw is not a minor side effect. See this image:

up.picr.de/37070551jh.png

Dr. Gomella at Grand Rounds in Urology in 2018 said: "it is one of the most horrifying side effects of anything that we do"

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Tall_Allen
Tall_Allen
in reply to GP24

I meant - the incidence is minor. The cumulative incidence for denosumab and zoledronic acid , respectively, was 0.8% and 0.5% at 1 year, 1.9% and 1.2% at 2 years and 2.0% and 1.4% at 3 years. Dr Saad's recommendation to reassess after 2 years, holds the incidence to under 2% (which I call minor). Compare that to the crippling effects of fractures and spinal compression.

My mother only had access at the time (25 years ago) to an oral bisphosphonate. She had a will to live until she suffered spinal compression and was no longer able to walk. After that, her quality of life was such that she declined all further therapy. To me, the certainty of delaying the first symptomatic skeletal related event is well worth the less than 2% risk of ostenecrosis of the jaw (which may be even lower with prophylactic dental work and good dental hygeine.)

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Coolpops
Coolpops
in reply to Tall_Allen

Mr t that’s my urologist that is treating me what do u think of him and what he told me about my treatment

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Tall_Allen
Tall_Allen
in reply to Coolpops

What did he tell you?

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Coolpops
Coolpops
in reply to Tall_Allen

One more lupron injection and we’ll stop after that since I am responding well to it but keep on taking cassdex and see him in 6 months no radiation nothing and haven’t done any

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Kevinski65

I've been getting a yearly dose of zometa. Is that ok? Some people are getting it like every 4 months.

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Tall_Allen

Listen to Fred Saad's presentation. He doesn't think it's OK to skimp on the dose. What are your DEXA scans telling you? Did you need it in the first place?

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Kevinski65

I have osteoporosis in a vertebrae. Other than that it says yearly on the infusion bottle. I'll have to see what my next one density scan says.

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Kevinski65

I used to take celebrex with it but my Rx benefits kept tucking it to me on the price.

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Tall_Allen

The package directions for people with metastatic solid tumors say "Administer 120 mg every 4 weeks"

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Kevinski65

I'll have to look at my next bone density test. I've been doing well on lupron and Xtandi. Stage 4 , 8 years out at NIH.

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Lulu700

Hey guy! I respect what you’re doing . I just had my first prolia shot due to osteopenia setting in . It has similar fear of jaw issues. Keep healing yourself and as always always keep. HopingForTheBest .✌️

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bryson43

having the injection every 2 months with no serious side effects

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easeytiger

I've been on a monthly dose of xgeva for 23 months. This month I asked my MO if this was still necessary and his opinion was that there should be no negative affect to go to 8 week intervals in my case at this stage.

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ctflatlander

My MO is giving me Xgeva shot every 12 weeks based on Optimize-2 trial. Label says every 4 weeks. No side effects. Bob

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tom67inMA

Interesting... A quick internet search says this about that trial:

"During the course of the trial, denosumab has partially displaced zoledronic acid as the bone-targeted agent of choice, following the comparison with zoledronic acid that showed denosumab to be superior in delaying the first skeletal-related event.20 Whether the frequency of administration of denosumab can also be reduced is not known and, because the mechanism of action is completely different, with no accumulation of the antibody in the skeleton, the results from OPTIMIZE-2 and CALGB 70604 should not be extrapolated to the use of denosumab."

From ascopost.com/issues/may-25-...

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Break60

I switched from monthly to every three months after two bone density tests 12 months apart showed normal. Plus when I switched from SOCADT to estradiol Patches my risk of osteoporosis went down reducing need for bone protection.

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Cantabrigian51

My famous MO prescribes Xgeva every 12 weeks. I have been on it since it was approved and my last bone density scan was normal.

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j-o-h-n

So who's your famous MO? (Այսպիսով, ով է ձեր հայտնի MO- ն:)

All Info Voluntary, Thank You...

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 10/24/2019 5:41 PM DST

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larry_dammit

😜😜😜. Sorry but I have been on the every 4 weeks now for 38 months as well as xtandi, can’t tell what side effects are from what. Tendon issues in both shoulders which has ran down into my hands. Don’t know if that counts or not. Hating this monster 😡😡

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j-o-h-n

Damn the monster. 😡😡 😡😡 😡😡 😡😡 😡😡 😡😡 😡😡 😡😡

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 10/24/2019 5:43 PM DST

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G2779

My father had to stop it as was draining calcium from body so fast he had keep getting calcium infusion -so they stopped him taking it, not sure what going happen going forward

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elainea53

My husband had a tooth that just broke in pieces. Mo took him off xgeva.

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HopingForTheBest1

How long was he on it, and was it every 4 weeks?

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Kevinski65

I had that, my dentist crowned it. I felt like a king.

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Magnus1964

I have been on xgeva for over a year, It seemed at first that I had cracking of neck and jaw. All of this is now gone.

There is now a new protocol for xgeva. You can now get the shot every two months instead of every 28 days. Good news for me.

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HopingForTheBest1

Interesting info. Where can I find more info about the new protocol for Xgeva?

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Magnus1964

I have been looking for information online but can't find anything. I will have to ask the research team the next chance I get.

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Max135

my travels (34 months) with the PCa have included a monthly shot of Xgeva (once every four weeks). a recent visit to my GU Medonc in Houston had me asking if I for sure needed a monthly shot and his comment was most likely not. again we are trying to promote bone health and for sure there may be reasons to take it month but if your active and in good health then every three months should be good. just my personal view..... not a doctor! No issues taking xgeva monthly so its truly a person thing.

Ken

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Kevinski65
Kevinski65
in reply to Max135

I thought the only real difference between zometa and denusamab was that denusamab didn't whistle through your kidneys.

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Max135
Max135
in reply to Kevinski65

Kevin

I would imagine this is true since MD Anderson has it at the top of the list for bone health. Sorry to say I am not sure on the mech difference.

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Bebby1

My husband has monthlyabout 7 months now

Got teeth checked prior

Has had them checked since

So far no problem

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Prostratehelp

I have been on a 4 week regiment of Xgeva for almost 2 years without any side effects. You must have regular dental checkups and take 1200 mg of calcium with Vit D every day (600mg in AM and 600mg in PM).

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Lulu700

I hadn’t heard about am p m splitting D . Interesting ,I’ll start this . Thanks

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