I just spoke to an MD PhD who had breast cancer and who is taking denosumab as a prophylactic to prevent the spread of her breast cancer to her bones.
She is doing this under the supervision of a breast cancer oncologist at UCLA.
The morphology of prostate cancer and breast cancer is very similar and they are sort of related.
She insists that I explore it as a prophylactic for the spread of my prostate cancer to the the bones. She has actually offered to find me the right doc at UCLA to supervise this. She has indicated to me that side effects are not a major issue for denosumab.
Any thoughts of comments on this, whether practical or theoretical.
Has anyone heard of such a use of denosumab? Are there any other such prophylactics that you have heard of?
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cesanon
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That was the hope several years ago. But then 2 major RCTs (TROG RADAR & STAMPEDE) proved it didn’t. However, the combination of Zometa and Celebrex improved survival by 22%.
The only thing similar about them is that they are both used to treat bone density problems. Zometa is zoledronic acid, a bisphosphonate. Denosumab/prolia is a monoclonal antibody. Chemically, they are not similar in the least. I think it's a stretch to conclude that research done on one applies to the other.
They have different modes of action, but they do the same thing. Xgeva/Prolia (denosumab) is a RANKL inhibitor. RANKL otherwise stimulates bone resorption (osteoclasts). Zometa (zoledronic acid) directly inhibits osteoclasts. So both accomplish the same thing in the end. They both affect the bone microenvironment by reducing osteoclast formation.
I agree that the combination of Xgeva+Celebrex remains unproven, and I know of no clinical trials to test it. But Celebrex is a safe NSAID (as safe as other NSAIDs) that is often prescribed for chronic pain, as one gets from bone metastases. Can you think of a reason why a man with painful bone metastases should not take the combination, since he needs a bone strengthener and an NSAID anyway?
I certainly would. My point was that just because two very different compounds have some similar effects, you can't draw conclusions about one from clinical trials using the other. I get a prolia shot twice a year, and if it might help prevent bone mets, so much the better.
It's use in men with mHSPC is controversial. It has never shown a benefit yet in those kinds of patients. Because side effects increase with cumulative years of treatment, it is often withheld until mCRPC, for which its benefit in preventing fractures is well known. There is no benefit in taking it when BMD is normal. If you've always exercised a lot, you may never need it.
How about the use of Celecoxib 200 once or twice daily for lumbar pain and sciatica. Any evidence of help preventing bone Mets? Also on Lupron and Daralutamide.
Celecoxib by itself has been shown to do nothing for bone metastases, apart from pain of inflammation. Nor does Zometa. However, combined they increased survival by 22%:
"However, the combination of Zometa and Celebrex improved survival by 22%."
A year or two later. Do you still think the current evidence supports Zometa and Celebrex as the best prophylactic against prostate cancer spread to the bone?
This was brought to my attention by a MO several years ago. Tha in addition to protecting against adverse skeletal related events and bone mineral loss, that denosumab may alter the bone micro environment in a way that makes it less hospitable for new bone mets to be established. I started on a Prolia regimen promptly (replacing my alendronate). I think this is more important to undertake early, before any bone mets and even at BCR (which I did) and still HS ideally. It is a preventive measure against progression and not a treatment for what is already established. That may be why such trials as STAMPEDE did not confirm in their arms. BTW I also take celecoxib 400 mg daily. I am still HSPC and negative for mets on scans so far, 12 years after BCR. My personal opinion is that a bone strengthening regimen such as denosumab or Zometa or an oral bisphosphonate should be considered by every man with APC, and not wait until osteopenia on DEXA scan. Exception being those with significant dental problems at greater risk for ONJ.
MateoBeach, I conclude from what you write that for someone with metastasis, even if low-volume / zapped, clean scan and with undetectable psa, there is no use taking bone-strengthening medication as a prophylactic against more PC spreading to bones - it's too late?
That sounds like a good situation for denosumab: to protect against skeletal adverse events, keep bones as strong as possible and maybe make bone less hospitable for forming new mets. Even though it is not proven yet. Why leave it on the table? Is my bias. Risks are low. I do suspect that earlier is better.
Thanks. Then I may have even more motivation to follow my general practioner's advice to take biophosphonates (zolodrenic acid) to counter osteo in hips and wrists (in spine BMD is perfect). I have been resisting, afraid of side effects. Am instead exercising (jumping from a chair, landing on one heel at a time) with proven benefis.
Perhaps I should do zolodrenic instead or both, although doc said that medication might nullify the exercise effects.
Is denosumab likely to be superior to biophosphonates from a prophylactic pc view? I understand denosumab, once started, has to be taken for life, which scares me a bit
My apologies, MateoBeach, for harassing you even more, but I must get back on your assertion - "risks are low" for denosumab.
Have you - and the other Forum members with apparently positive experience of Xgeva/Prolia - really not experienced any of the side effects listed below? Granted that not all reported SEs are due to the medication, it does seems that one would have to be lucky not to experience any one of those:
The safety of Xgeva was evaluated in three randomized, double-blind, double-dummy trials [see Clinical Trials] in which a total of 2841 patients with bone metastasis from prostate cancer, breast cancer, or other solid tumors, or lytic bony lesions from multiple myeloma received at least one dose of Xgeva
After a median duration of exposure to Xgeva of 12 months with 120 mg of Xgeva every 4 weeks as a subcutaneous injection, the most common side effects were:
Fatigue 45 %
Nausea 31 %
Diarrhea 20 %
Dyspnea/Shortness of breath 21 %
Cough 15%
Hypophosphatemia 32%
Severe hypophosphatemia (serum prosphorus less than 2mg/dl) 15%
Hypocalcemia 18 %
Headache 13 %
The more severe SE:s i.e. osteonecrosis of the jaw (5% in the second year) and atypical femoral fracture (low percentage but increasing over time with medication, can´t find the numbers) are unlikely, but added together are not insignificant. Discontinuation of Xgeva on its own has a risk of severe side effects including osteonecrosis of the jaw, no number found.
I am not out to criticize, but to get input on making a decision whether to go for Xgeva (or possibly Prolia) despite apparently considerable SE:s, given my osteo (hips only, not spine) and GS9.
Thanks for asking this. I personally have no side effects at all with my Prolia injections. Not at the start and none now. I have noticed that many here who already have known bony mets can have substantial pain at sites after injections, along with fatigue. I have no known bone mets on scans including PSMA PET. That may be why I have no symptoms: no lyric lesions get activated. Note that I am taking it to prevent bone mets and weakness and not to treat them. That is why I started early after BCR, with alendronate initially.ONJ is a real concern but real-world experience seems to be more like 1-2% rather than 5%. And much of the risk may accrue to those with dental and gum disease. That is why I advocate getting all needed dental work done and up to snuff prior to starting. With that perhaps the risk may be 1% or even less. Dental status is not generally broken down in the trials. But most reported cases and series come from dentist practices with ONJ related to dental issues.
Much more difficult decision on risk vs benefit if one already has bony mets, especially if already symptomatic. One could try a dose and see.?
Thanks, this clarifies. I have had a single met, to right iliac bone, no pain involved, it was zapped six months and I have a clean scan now, PSA less than 0.1 since then, no dental issues. I guess that puts me at a relatively lower risk for (serious) SE:s.....
As you write, try a dose and see, of course - but there are the warnings never to stop it or these terrible things can happen, can´t find numbers on it. "The risk of fracture, including multiple vertebral fractures, increases when Xgeva is discontinued, and new vertebral fractures have been reported in as little as 7 months following discontinuation. The risk decreases to pretreatment values within 24 months"
A(nother) reason one has to be on it for life: "Bone density returns to pretreatment values within 18 months of the last injection of denosumab". Isn´t that a downer? My osteo has built up over long time, Xgeva makes it a lot better over some years, and then all that has been built up (indirectly, thanks to of osteoclast inhibition) vanishes in just 1,5 years after discontinuation, if one has the need to stop it.
One - hopefully the last! - more query on the issue. The indications for anti-met effects for denosumab are because of it being a RANKL-inhibitor, rather than a general bone strengthener, is that correct?
I ask because I am doing a 40 times per day jumping down on each heel exercise, which has already improved my hip osteo a little, which I find attractive athough I havn´t done a head-to-head comparison betweeen the research on it and denosumab. Can anything be said on the likelihood of anti-met activity of bone-strengthening from exercise? Can´t find anything on it.
Good questions! Good on you for adding plyometrics to amplify weight bearing effects. But do be careful, landing on heel with rigid knees will create compressive shocks in the spine and risk of compression fractures. I would do two legged jumps up onto a chair high stable platform, then back to the ground on both feet. Great strength exercise. Old fashion “skipping” also gives good plyo loading.
I only know that denosumab seems to inhibit metastasis of PC to bone. Suggested in clinical trials, cannot claim it to be proven. It is a reasonable possibility because it does alter the bone micro environment through its RANKL inhibiting mechanism of action. For this reason I personally favor it over zolendronic acid for my bone strengthening and protective regimen. Clinical trials of zolendronate have been generally disappointing for PC mets such as in STAMPEDE and :
As for stopping it, as long as we have PC and especially with ADT in my foreseeable future, I expect to continue it indefinitely. After some period with Xgeva monthly dosing (optimal period undetermined), one could drop down to the six month dosing with Prolia for maintenance. Again, not proven, but reasonable. Surely more clarification will be forthcoming before long.
As has been pointed out, metformin also has some effect via RANKL, among other pathways. Certainly does not effect bone to anywhere near the degree of denosumab. I include both metformin and denosumab in my own PC regimen. N =1, but 12 years after BCR still HS and M0. Making no claims but very grateful for that.
You can be not only grateful but proud for being HS and MO after 12 years, probably helped by your astute regimen.
I land on a slightly flexed knee; my body refuses to obey my wish to land on a fully rigid knee, so I don´t think there´s a risk of a compression fracture. Hurt my foot soon after starting so dropped the height 4 cm after that no problem. T in hip from -2.5 to -2.2 in six months perhaps thanks to the jumping. Wrist/forearm is even worse so I arrest falls towards a wall with one wrist at a time.
Because of this I wouldn´t be considering denosumab if it wasn´t for its intriguing very possible , even probable?, met cancer preventive effects. The scare stories on denosumab must be relatively rare. A possible restriction on using immunotherapy is a concern but effects on the immune system are probably overblown.
Will start metformin, the research is adding up on it.
I started monthly last December then every 3 months , you have to watch the calcium when raking xgeva. The oncologist indicated it strengthens bones and prevents further Mets so why not try it, he has been correct so far with the treatments. I had no jaw issues so far.
Using Denosumab - and its more intensive form Xgeva - in connection with PCA to guard against bone mets is absolutely standard treatment here in Denmark.
Can you be a bit more specific about what “absolutely standard” means here? For example, are these agents offered to post-RP patients independent of BCR, or only after BCR? Does this continue if/when BCR requires further treatment, such as ADT?
Can’t tell you, I am not a doctor. But I know that in Denmark Denusemab is given routinely when you have bone mets - and that you shift to Xgeva when those bone mets expand. That will to my knowledge always include at least adt treatment as well.
Not exactly - same active compound, but: denosumab/Prolia is injected once every six months - whereas Xgeva is injected once every month, so it's a more intensive version of the same treatment.
Yes, they were given distinct trade names in order to differentiate between their unique dosing schedules and indications for use. How they are used is different, but strictly speaking, the two are the same drug.
I received my Xgeva every three months, and has done an excellent job in protecting my bones from further mets. The jaw issue, if you need some extensive dental work, could be a problem down the road, just use good dental hygiene.
My untreated metastatic cancer psa 9000 was treated for 12 months with monthly Zoladex and denosamab injections along with daily Casodex for 12 months. Then swapped Casodex for Enzalutamide for 4 months. Then Zoladex and Deonosamab were extended to 3 monthly and Enzalutamide swapped for Aberiterone acetate and Prednisolone for now 3 1/2 years.
Hi cesanon.Thanks for info. Looks like I am back in the loop for more answers. PSA kept rising fast after biopsy last January. 2021. Went to over 1000. So I started reluctantly on ADT. Bicalutamide for 28 days. Started lupron 2 weeks ago. Have started getting more active again to keep body a bit fitter. Am77 yes young haha.
Yes I was put on Prolia when I had lymph nodes radiated and went on Lupron which is tough on bones and on Xgeva after a scan found bone mets. Very common . I switched to estradiol patches which are not as tough on bones or heart and therefore stopped Xgeva.
No. After a couple years I took a one year hiatus. I had a bone scan which showed no reduction in bone mass so I decided to stop Xgeva. Plus since estradiol has been shown to not have the impact on bones as does Lupron or it’s ilk, Xgeva became unnecessary.
I'm on denosumab (Xgeva) for onset of osteoporosis. If I was fully aware of it's horrible side effects and also up to speed on good bone health supplementation I would never have gone for it. Once you start you are advised not to go off, however long term use can cause sudden femur fracture and/ or jaw necrosis. To go off it sparks a rebound effect initiating spinal compression fractures. It does work for stopping the onset of osteoporosis but I feel a timely use of a bone health regimen could be a better option. I'm not sure about it's successful mitigation of bone mets. I haven't even touched on it's day to day side effects.
Yes, Xgeva is to help make your bones stronger and resistant to cancer cells.I developed osteonecrosis of the jaws and extreme joint pain in my right shoulder.
I was on Xgeva for 8 months. Now off for 9 months and osteonecrosis is still not healed.
Be aware of the adverse reactions.
They say only 5% are affected. If you have or had dental issues be aware!
FYI. It's been six years since my prostatectomy. At end of year five years was put on Prolia (22.5 mg. quarterly) and 1,000 mgs. calcium (daily), to prevent/slow metastasis to bones. In September, PSA remained below 0.20 but it's rising steadily - but so far nothing in bones - hope it stays that way. I'm just sayin.'
This is a tough one. Zoledronic acid seems safe and you can get off it but, despite having similar osteoclast inhibiting action as denosumab, the talk of the town is that is that it is the latter which inhibits metastasis. Should one dare go for it in spite of a percentage of scary side effects and being hard to stop? I understand its anti met activity is unproven.
Xgeva monthly for 3 years. Then changed to every 3 months "so teeth don't fall out", this last year and a half. Also take a total 400mg generic Celebrex every day as MateoBeach does. Am exercising (jumping from a chair, landing on one cat at a time) with proven hilarious benefits.
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