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Looking after those bones: Zometa or Denosumab for metastatic castrate resistant prostate cancer

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Looking after those bones: Zometa or Denosumab for metastatic castrate resistant prostate cancer

In short

Recommendations are that men with metastatic castrate resistant prostate cancer look after their bones with one of two bone protecting agents.

At the ASCO (American Society of Clinical Oncology) 2019 meeting, Dr Bertrand Tombal reported that despite this, only about one third of eligible men are getting these bone agents.

If you have metastatic castrate resistant prostate cancer, and are not on one of these bone agents, there may be good medical reasons for this, but this may be something to discuss with your doctor.

More detail

Two bone protecting agents:

  • Zometa (zoledronic acid or zoledronate); and
  • Xgeva (denosumab, a monoclonal antibody) have been available for some time.

In Australia both treatments are available for a nominal cost on the PBS for men with metastases due to castrate resistant prostate cancer. 

Studies

The ERA-223 clinical trial of Zytiga (abiraterone) with Xofigo (Radium-223) was stopped when it was found that the combination caused a significant increase in the risk of fractures and death.

The EORTC-1333-GUCG/PEACEIII clinical trial was in an early stage. It compared enzalutamide with a combination of Radium-223 plus enzalutamide for men with few, or no symptoms of metastatic castration-resistant prostate cancer.

Seeing the ERA-223 results, the researchers changed their study rules so new subjects should take bone protection agents.

In the men who had not had the bone protection agents, after one year there was

  • for men with enzalutamide: a 12.4% cumulative risk of fracture;
  • for men with enzalutamide and Radium-223: a 37.4% cumulative risk of fracture.

In the men who did have the bone protection agents, starting 6 weeks before treatment, after one year there was

  • for men with enzalutamide: no fractures;
  • for men with enzalutamide and Radium-223: no fractures.

I'm not a doctor, but there seems to be a clear message here!

Jim

 

 

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Kezza2

Thanks JIm,

I am just off to give myself a shot of Xgeva.  I had not heard of these studies before, but as usual my med onc was across it, and that is one more thing I can do to preserve QoL.

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Chalkie

I have been on Zgeva for a number of years now - once a month.  I recently had a fall where my leg was caught in a deep hole.  I was amazed that i had no issue.  I could have been a fracture - perhaps this drug protected me.   While on Zgeva I was on xtandi for about 6 months and lately I was on Lut177 (3 infusions) earlier this year.  My oncologist comments on recent scans were that my bones were good.  (Although all i see in the scans are lots if mets)

Chalkie

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GrahamW

I have been on Xtandi for about 2 years now. I get a shot of Xgeva (Denosumab) every 3 months at the same time as my Zoladex, and my bone density is improving, based on my last densitometry test a few weeks ago. Femur/hips/spinal area is normal now, whereas a few years ago I was in the osteopenia range. And keep taking a vitamin D/calcium supplement is the other advice I get, and follow. I should also mention that my oncologist insists that I have a regular exercise program.

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timbaker

That does raise the question of frequency of Denosumab. My oncologist wants to give it to me every six weeks but I had read some research that suggested it hangs around longer than first thought and could be stretched out to three monthly with adverse effects. With some prompting from me my oncologist agree to three monthly about a year ago and haven't had any issues and I exercise pretty strenuously. I'd be curious to know others views on frequency and any research to support  them. Thanks, Tim

 

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Patrick Turner

Early last year I was given 3 bi-monthly shots of Denosumab over 4 months, and not long after and before the next shot was due I got a sore lower right jaw, and the beginning of hole in skin covering jaw, ie, the start of lower jaw necrosis. I refused to have another shot, and a dentist found the skin hole and an oral surgeon confirmed dentist was right. So, I searched around online and found that a man only needs 1 dose each 6 months, because its effects fade down, and having 3 times the normal amount while having been on long term ADT there is a big risk of jaw necrosis. I also read a German report from 10 years ago that said any tinkering with bone density with drugs did not reduce the chance a man would get bone mets. Some docs believe bone medications slow down or prevent bone mets forming. Well maybe. But I think my bone mets may have begun before diagnosis in 2009 with a Gleason 9 when I was wonderfully healthy and cycling fast over long distances, and with above average bone density. I bet its now low, and because of arthritis in a hip, I can't cycle, let alone jump about in exercise that is The One Thing that promotes bone health, even when a man is on ADT for years.

The last MRI some 6 weeks ago of my R hip indicate bones are OK and sure, the 2 pea sized mets are there, but not yet big enough to cause bone weakness and fractures.

I have PsMa Ga68 scan tomorrow, to review what progress if any has been made with Pca after 4 shots of Lu177.

I might need a 5th Lu177. I'm on Enzalutamide since a month before 4th Lu177, and this is supposed to supercharge effect of Lu177. Well maybe. Maybe Psa zooms up instead of down. But I may never cycle again. OK, so I just potter about at home. I'll swim again next summer, but an hour in the water is nothing like a good hard cycle ride of 3 hours. And swimming does nothing for bone density and a radiologist who did a BD test years ago told me he had 25yo elite swimmers from AIS who had real fragile bones, because there is no weight bearing and no impacts. Astronauts returning from 6 months at a space station are in a terrible state, bone and muscle wasting....  We NEED gravity. 

Biophosfonate acid or Aclasta was a drug I was given maybe 2014, and its effect is permanent, and can also cause jaw necrosis. So having too much of this is irreversible so the lower can get big holes in bone and flesh, QOL goes out the window.....

Keep well. 

And was it not just so wonderful when Ashleigh Barty won the French Open? What a gal !

Patrick Turner. 

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Charles Thurgood

Greetings Jim,

I have completed 4 Lutetium treatments which brought my PSA down from 730 to 70 but after 2 months as it is back up to 310 a 5th. round is being considered.

Back in 2016 monthly Denosumab (XGEVA) 120 mg. was added to my 3 monthly Zoladex injections, as I am facture free perhaps this supports the observation you have posted.

 

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Kezza2

Thankyou to all who have provided their experiences with Denosumab et al.  However, a trend seems to be developing within those who have received Lutetium 177.  While initial results appear good, in a number of instances (as above) they do not seem to persist.  Now, not wanting to pre-empt the results of the trials, this information would be very valuable to those of us who are not yet on Lutetium, and / or are contemplating our next move.  I am currently trying to decide between :

1/  Being included in TheraP trial - PSa currently 89, and first possible  Lu177 treatment 23July.  (ie do I hang out for 6 weeks ??)

2/  Starting Cabazitaxel immediately (which would preclude me from the trial), or

3/  Borrowing $10,000 to start Lu177 immediately (which would probably also preclude me from the trail) and lock me into the full cost user-pays regeim.

Is it possible for those who have had or are having Lu177 to let Jim know their current situation, and for this to be developed as an anonymous data set ???  It would certainly help in my decission making.

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Admin

Kerry

Barry Elderfield has a fairly comprehensive data set in his head.

Can I suggest you give him a call about the lutetium story?

Please call me after that if you want to talk through the choices you face.

Jim

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Admin

Kerry

Barry is expecting your call.

Jim

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Kezza2

Thanks Jim.

I am off to see my medonc today, and a follow=up with my GP, so I will give Barry and you call tomorrow

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