Bone health: An endocrinologist talks to men with advanced prostate cancer: Minutes 25 July 2014

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Advanced Prostate Cancer

Telephone Meeting 

Minutes 25 July 2014

These Minutes are general in nature and not meant as advice. You must consult with Health Professionals for advice.

Minutes courtesy Nev Black

 

Guest Speaker - Dr Jane Holmes-Walker 

 

Person #1:  I was diagnosed in December 2012. I was diagnosed with metastatic cancer at first diagnosis which was a bit of a shock as you can imagine. I found your website fairly quickly. I am working full time so this is my first opportunity to join in as I am currently on holidays. I started hormone treatment almost immediately. 

I was taking Zoladex and Bicalutamide  Ed.(Cosudex). I took that up until May and then I stopped taking the ADT in May because my PSA dropped from 20 to .01. In the meantime I also had radiation. I had a month of radiation to my pelvis and prostate. Then a couple doses of about 65 grey in total to a couple of spots in my upper spine and back, lower spine. 

With the combination of the radiation and tablets has put my PSA down to .01. The last time I saw the radiation oncologist he said he would call that remission. I am due for my first blood test next week. 

I have found the  www.jimjimjimjim.com  website very useful. I also found a couple of resources in the US where they were www.healingwell.com  and I found out about Stereotactic Radiation to the spine. 

Everybody said just take the tablets. When I read about that I found a doctor at Royal Shore Hospital who said he was quite happy to the spine radiation as well as the pelvis radiation. So that has been very successful. I have been working full time throughout the process. Apart from being diagnosed in the actual first place I feel very lucky. I am 52 now.

 

Chairman Bruce  Have you been recommended an exercise program?

 

Person #1:   Not a specific exercise program. I have been keeping up walking and cycling. I go to the gym once a week. I have been recommended to do weight bearing exercise. I have had a couple of density scans.

 

Chairman Bruce   That is the important thing or otherwise there is as time goes on a risk of loss of bone density.

 

Person #3:  asks Person #1  now that you are on intermittent hormone therapy and you have been doing searches around the net one of things you may have come across is Dr ‘Snuffy’ Myers in the States and a few other doctors who suggest taking Avodart while you are on intermittent hormone therapy as a part of your maintenance program? You may be interested about talking to your doctor about it, or doing a search. 

 

Person #1:  I am going to a PCRI Conference in September about prostate cancer research and they run a conference once a year for patients. Dr ‘Snuffy’ Myers will be a speaker there. It is his treatment that pointed me in the direction of stereotactic radiation therapy.

 

Person #4:   I will just briefly update you on my situation at the moment. I had an unsuccessful radical in 2003. I have been on continuous hormone treatment since that time. Through last year and this year my PSA was going up reasonably quickly 8,10,12 to 16. Then around last Christmas it jumped from 24 to 61 and since then it has gone up a bit further to about 65.

I have been talking to my medical oncologist about that and there were various options. One of the options was to try and get onto a clinical trial with Enzalutamide, a new drug. So it is a phase four clinical trial. The initial part of it everybody gets the active drug. There is no placebo in the initial part of the trial. There is some placebo in the second stage. 

 

With various delays out of my, and my doctors’ control, I finally got onto that and started taking the pills on the June 18. Prior to June 18, I was getting some pain in the pelvic area. The final CT scan identified where most of the cancer was and that was a 4 cm metastases in the right pelvic lymph node. I was getting pain from that area on a constant basis up until the time I started taking the Enzalutamide. Within a day or so of taking the Enzalutamide the pain stopped and has not yet returned. My PSA has dropped within the last four weeks from 65 to 38. I am now on the regime of having another test for that on the trial in eight weeks’ time and with a bit of luck it will drop a bit further. 

 

I was talking to another gentleman who got on the trial in January before me and prior to that his PSA had gone up to about 80 and it skyrocketed to 400 that was before he started on the trial. He claimed to me that just after four weeks his PSA had dropped from 400 to 0.27. 

On the day I was talking to him it had gone up to 7 and that was about a week ago. There is probably a fair bit of variability on the way different people respond. I think most people get some sort of benefit out to it. I am hopeful my PSA will continue to drop from 38 down to something lower and I can maintain a lower PSA for some period of time. That is my story at the moment.

 

Chairman Bruce   Invites Tony_Maxwell to introduce guest speaker Dr Jane Holmes-Walker.

 

Tony Maxwell:   My urologist quickly flipped me to my now medical oncologist, A/Prof. Howard Gurney, and about after a year on the hormone treatment he said to me this is looking like a long term thing which it has turned out to be of course and we need to make sure that we cover some of the other issues that are related to being on ADT, the bone density and the general biochemistry of your body. 

 

He referred me to Dr Jane Holmes -Walker who I have been with ever since and the combinations from the small number Zometa infusions earlier in the period and then basically a regime of Calcium and Vitamin D since then I have able to maintain my bone density at acceptable levels. A little bit of Osteopenia, which hasn't seemed to have gotten worse over that time period. I am due to get another test done now. I am very pleased with what Dr Jane has achieved in terms of my situation.

 

Dr Jane has put out documents I think in the medical journal of Australia or journal articles in regard to all of this and she will probably be talking a bit about that. So I would like to introduce and welcome Dr Jane Holmes-Walker.

 

Dr Jane  Thanks. I have been asked to talk about maintaining bone health in prostate cancer. So I will cover the whole spectrum of prostate cancer, from early diagnosis up to advanced prostate cancer, and what the different treatments that you can use across that span that will help preserve bone density in men.

I am just going to start with a bit of background about the prevalence of bone density these days in men with prostate cancer. The reason we have become concerned about all these is because prostate cancer does indeed have a very good survival from diagnosis. In the fifth year 98% of men who have prostate cancer will still be functioning well. There is a 93% survival at 10 years. Obviously prostate cancer is something that can occur in young men but it certainly is much more prevalent in men as they age.

Now given that you can survive for quite a number of years afterwards you need to focus on some of the negative consequences of the treatment which allows you to survive for that length of time. It is the adverse effects on things like bone density and if we have got time I will do a little bit on the cardiovascular risk even though that is an area still under investigation.

Androgen Deprivation Therapy is a common treatment in prostate cancer does cause significant loss of bone density as has been discussed already here today. As a consequence of that it does increase fracture risk. I think we need to have a look at what we can do to prevent the consequences of Androgen Deprivation Therapy.

The other thing I want to mention is that while Osteoporosis is often thought of a disorder of women it is actually also a disorder of aging men as well. While fractures in the elderly certainly increase quite significantly particularly in those over the age of 70 years. It is worth noting that though three out of four hip fractures occur in women, one in four hip fractures do occur in men. 

They are probably the fractures that carries the most significant consequences.  About a 32% mortality at one year after every facture of a man over the age of 70. That is a significant consequence of fracture. That means that fractures in elderly men and women are as fatal as heart attacks. What we are going to do is look at what sort of treatments you can use to try and prevent that.  

 

I guess the other thing is if you are a young man picked up with prostate cancer, around 60 years there is still about 1.6% of men at that age who already have Osteoporosis and that gets up to about 20% of men who have Osteoporosis by the age of 80 years.

Vitamin D deficiency is becoming quite common in Australia that is probably because we are very good now at using sunscreen. The Vitamin D deficiency exacerbates the development of Osteoporosis.

 

Person #11:  I am just curious you said the mortality rate was 32% after the first fracture?

 

Dr Jane  Significant fractures like hips fractures if you are over the age of 70 then the mortality is 30%. It is not as high as that in the younger men with fracture but certainly if you are over the age of 70 then there is a 30% mortality. That is similar to heart attacks mortality in over 70 year old men. There is still a bit unclear of mortality in men and woman and heart attacks. I just want to emphasise that osteoporosis is a benign disease and it does carry a mortality  as well as a morbidly.

 

Person #11:  I found that interesting thank you.

 

Person #13:   Can you please outline what Endocrinologists do as a speciality?

 

Dr Jane  An Endocrinologist can be described as the responsibility of  management of excess and deficiency of hormones. Osteoporosis I guess is considered a disorder basically involving the deficiency of hormones particularly in women because they lose Estrogen from around the age of 50. Some men also become Testosterone deficient even in the absence of treatment like Androgen Deprivation Therapy. Certainly once you use Treatments like Androgen Deprivation Therapy by definition, you are losing Testosterone and there are managing consequences of that and that is predominantly Osteoporosis.

We also manage Diabetes a fairly predominantly a deficiency, of Insulin. Thyroid deficiency which may just be hormones coming through your thyroid.

 

Person #13:  Are you involved in any research as well as advising treatment?

 

Dr Jane  Absolutely. The place I work is St Vincent’s Hospital, Westmead that gives me the great privilege of being involved inside a number of research studies. Most of my research is in the diabetes field. We are investigation Androgen Deprivation Therapy and the development of diabetes as well. My other research is involved in Type 1 Diabetes and the management of Type 1 Diabetes.

 

Chairman Bruce   The situation was explained to me at a medical meeting in Brisbane a few years ago that as men age they get less well-endowed and the testicles get a bit smaller and smaller and that means a bit less Testosterone and that means there can be seen the body start to decline in their  Bone Density. To a ratio level that are less than what they used to be but not so much to be a risk. Some of us as we get older start off on the back foot rather than the front foot.

 

Dr Jane  So some men even once they are diagnosed with prostate cancer might already have some androgen deprivation therapy. They may already be mildly androgen deficient and certainly even in the  general population that mild androgen deficiency has been shown to accelerate with aging and there is some debate about at what levels you start to replace hormones when your levels are low.

 

Person #14:   I had two years of continuous ADT after that I only had partial recovery of my testosterone. I went out seeking how much testosterone do I need to maintain good bone health. What I have found is that in spite of everyone believing it is Testosterone that is high in men greater bone density it was actually Estrogen in the more recent studies and they compared both the Testosterone and Estrogen to bone density test and come up with the primary driver. I had my Estrogen tested to see if levels were adequate to maintain bone health.

 

Dr Jane The difficult thing is measuring Estrogen in blood is not necessarily a reflection of what is happening with the bone. Some of that Testosterone is actually converted very locally in bone and some of the effects of androgen deprivation therapy might also reduce that conversion of the testosterone to each of them in bone itself because a blood level doesn't necessarily always reflect what is happening in the bone itself because it is a local conversion.

Bone levels below eight are associated with or it is tolerated decline with bone density that would otherwise happen. Testosterone levels above eight probably don't and are considered bone loss.

 

Person #14:   My testosterone is six as of the last test. It is interesting you say that. So it is happening at bone level.

 

Dr Jane  So I thought I would go more specifically to what affects Androgen Deprivation Therapy can have on bones and fractures in a difference to age related bone loss authority occurring. What is really interesting about men found to have prostate cancer, even before they commence androgen deprivation therapy, is they in general have lower bone density than men who don't have prostate cancer. They are certainly then at a higher risk for having lower bone density right from the outset. That is in their age to similar men. 

The androgen deprivation therapy then causes an accelerated loss of bone density. Normally you would lose maybe 1% of your bone each year just with aging. The first year of androgen deprivation therapy you can lose as much as 8% of bone in one year in the spine and about 6% from (inaudible). 

So if you are already started losing bone density after one year of therapy you could have lost quite a significant amount of bone.

Vitamin D status should also be evaluated at the start of androgen deprivation therapy. It is generally recommend in anyone who has reduced bone density with the Vitamin D levels just a little bit above the general population level above 50. Vitamin D levels around the 75 for men on ADT. 

The main reason for that is because it has some effects on another hormone called (inaudible) which also causes bone loss and vitamin D when it is about 75 maximum (inaudible) causing bone loss.

Androgen Deprivation Therapy seems to specifically affect spine bone density much more than hip bone density. It is the type of bone that (inaudible) that is particularly involved in maintaining and that is what we call the trabecular bone, which is the mesh like bone in the centre. In the hips it might be reflective in total bone density rather than just general bone density. 

We have got a bit of a problem that when we try and measure bone density in the spine in men, it is often difficult to get a very accurate measurement and that is because men often quite physical in labouring jobs, and they do have much more osteo arthritis in their spine. 

 

That type too artificially elevates bone density on the DEXA Scan, however you can get around that problem by doing Quantitative CT bone density. I still think DEXA bone density is the best screening test. It is recommended to be done in the guidelines when all men starting androgen deprivation therapy. The main reason I would do a Quantitative CT bone density would be, if the spine bone density looked to be high normal, but the hip bone density looks to be reduced, that would generally suggest that there is quite a good coordinateness between to two measurements, and therefore that the spine bone density has been artificially elevated and we are not getting a very good assessment of bone density within that type of study. 

 

I recommend to men who have been found to have reduced bone density in an osteopenia that they should have a Thoracic Spine X-ray and it is particularly on the lateral views that you can pick up on the anterior wedge compression fractures. They can be completely asymptomatic or you might just have non pacific aching in the back, which you have never really thought too much about. That could actually, in the X-ray show some compression fracture, even in asymptomatic men. If they are there then you know that all though the DEXA is relatively high bone density in the spine, the fracture is only something about bone strength. This will advise that there is most certainly osteopenia or osteoporosis in your spine. That would be an indication to start treatment with an active agent to prevent bone loss immediately.

We will compound the risk for the osteoporosis in fact having a low vitamin D which I have mentioned. The longer you are on the androgen deprivation therapy the greater your risk. Other things like lifestyle, having had a history of drinking a lot of alcohol over a lifespan or continuing to drink moderate alcohol. What we call 40 grams a day or four standard drinks a day would be enough to contribute to accelerate bone loss. There are obviously some lifestyle things that can be done outside of your therapy for your prostate cancer which will also help to protect your bone density.

The status shows that about one in five men who survive five years after the diagnosis of prostate cancer will get a fracture if they are treated with androgen deprivation therapy and that compares to one in eight men who don't get androgen deprivation therapy. We have worked it out, that is about one extra fracture for every twenty eight (28) men who are treated with androgen deprivation therapy over and above the population with the risk of having a fracture over a five year period. Does anyone want to ask any questions about that information?

 

Person #17:   I have been on ADT for about three years now. I was never told what dose rate of calcium or vitamin D, I was supposed to take. Is there a recommended dose rate?

 

Dr Jane  Yes there is some good recommendations for maintaining bone health. It is generally recommended you have an intake of what we call one gram of calcium a day. One gram of calcium is equivalent in diet terms, to four serves of dairy. That might be a small cup of milk, 150mls is one serve. Small container of yogurt is one serve. Four slices of cheese is one serve. They are probably the main diet servings. Obviously ice-cream has some as well but I can't tell you what size serve you should have for your ice-cream to get your calcium. 

You can get a little bit from things like tinned salmon with bones and any other cured fish with bones. They also quite high in calcium. Our diet sources of calcium apart from that seem to be quite small and are not sufficient to really maintain bone health. 

If you don't have a lot of diary you can supplement that with 500mg tablets. If you have no diary you should probably have two a day. If you have some diary you could have 1 tablet a day would be probably enough to bring you up to a gram a day. It is recommended diet calcium is probably safer and better for you to use other than supplement tablets. A number of people have high cholesterol so they can't introduce that diet to their intake and that often leads to cutting out dairy. 

     

Person #17:    I am on about 500/600 caltrate plus vitamin D. I was just wondering whether or not if that was adequate enough?

 

Dr Jane  The recommended daily intake for vitamin D is 400 international units per day. Lots of the tablets now are made with 500 international units per tablet. If you are having one tablet a day then you are getting the recommended daily intake of vitamin D. That is enough to maintain vitamin D levels but if you are deficient you will probably need vitamin D above that.

 

Person #17:  The other thing is you mentioned bone fractures. I am also on a functionally Xgeva injection is that to prevent that?

 

Dr Jane  I will now talk a little bit about the treatments. When you have advanced prostate cancer those treatments have been shown to help reduce fracture. Most fractures are associated with bone metastases. It doesn't do a lot for the osteoporosis. It certainly does reduce fractures. About 20% of all fractures in men with advanced prostate cancer are the consequences of the chemo in bone and not from osteoporosis itself. Having said that 90% of fractures are from osteoporosis not from the metastases. Sometimes we need to do both treatments maybe a treatment that is bone specific for osteoporosis as well as the Xgeva for the metastases in the bone. Some treatments for osteoporosis do both.

 

Person #13:   Just to clarify one point. I just wanted to ask you if you can be more definitive about the calcium. The reason for asking that is sometimes the supplements are expressed as calcium, sometimes expressed as calcium carbonate and sometimes they have other co-factors as well. Could you please clarify that a little?

 

Dr Jane  So I often look on packaging at what they call elemental calcium. That means how much calcium is in all the different compounds contained within that calcium tablet and there is the amount of what we call available calcium for absorption. So a lot of tablets will have a total of 600 mg of calcium but about 500 mg is what we call elemental or available calcium. 

Some calcium is said to be absorbed more readily from the gut. The concentrated calcium is said to be absorbed more easily. In general I think the difference is that it is making the claim in the tablet, it more comes down to personal preference as a lot people do get side effects from calcium tablets. Some of the most common are stomach upset or constipation. I think it is important to find a calcium supplement that you can tolerate quite well without any side effects. That is why there is a multiplicity of different calcium tablets out there. If you look at the elemental calcium it should be 50 and you can get an idea of how much calcium you are getting.

We have talked a little about bone metastases and what their treatments are for fracture. It is known that once you get caltrate deficiency with prostate cancer about 80-90% of men who have tumours in their bones metastasis recognise the (inaudible) bone. That metastasis to bone does increase the osteoclast activity. In bone there are two cells, there is an osteoblast that builds bone and an osteoclast that breaks down bone. That also contributes to an increase in osteoporosis around a metastasis itself. That is why you are then more prone to fracture especially if you already have some osteoporosis that will accelerate that process locally around the metastases and contribute to the fracture.

 

It is also known that metastases of the bone, it much more likely, if you are vitamin D deficient. Vitamin D deficiency also changes osteoblast and osteoclast activity, which may be important in renewing some of the micro metastases from bone.

Only about 10% of fractures are in men treated with androgen deprivation therapy from metastasis itself. The majority is actually due to the osteoporosis.

I said I would mention some of the treatments. One of the newer agents that are now available for use in men is an agent Denosumab. I think it gets marketed as Xgeva in the prostate cancer setting and it is marketed as Prolia in the osteoporosis setting. When it is used as Xgeva it is used much more frequently and it is used in the osteoporosis process monthly or two monthly in the prostate cancer setting. Denosumab (Xgeva or Prolia) is also authorised for the treatment of osteoporosis in men. 

 

Probably in the last two years it has started becoming available for use in men. There has been a bit of a trick to using previous agents like Bisphosphonates, Binosto, Fosamax (alendronate) and it increases the (inaudible) because evidence has shown (inaudible) benefits for helping stop the progression of prostate cancer and metastasis in bone as well as helping with osteoporosis. 

There has been a bit of tit for tat using that agent a lot more in osteoporotic men. We can use that on an authority prescription when there is evidence that there is previous osteoporotic fracture or where the man is over the age of 70. Even if he doesn't have a fracture if his bone density is in the osteoporotic range we are able to use that.

As I was saying that bone is a balance of these two cells, osteoblast and osteoclast and our bone turns over all the time. It has always been broken down and repaired broken down and repaired. Some of the treatments we use, Denosumab and all the Bisphosphonate groups, we do have to be careful how much we do use them. Sometimes if you use them too much you can actually contribute to what we call atypical fractures. These fractures are not your typical osteoporotic fractures. 

 

They are fractures that occur in other areas and it is thought that is because if you slow down the rate of the bone loss you slow down bone repair. Then when you are walking around bones can get what we call micro fractures. The osteoblast and osteoclast activity is very important for repairing them day to day. If treated too much what happens is you stop repairing those little micro fractures and they can go on to become significant fractures. They tend to occur in funny spots like right in the middle of the shaft of your Femur and they tend to be like spiral type fractures. 

When you are on these treatments it is really important that people are monitoring how your bone is turning over. That might be found on blood tests or urine tests. If people are using these treatments without monitoring them that would place them at risk of some of these unusual fractures. In general if you are being provided by an endocrinologist or specialist sometimes it is a rheumatologist who have an interest in bone health generally should be monitoring for those sorts of things to make sure you do not get too much treatment.  

 

Some of you may have been on these agents and you get what is called a 'drug holiday'. That drug holiday is because particularly the Bisphosphonate group of drugs they stay in your bones for quite awhile and when you stop the drugs they also continue to have some activity but if you gradually wane over time and allow that bone repair mechanism to recover. 

Once they have recovered those agents should be available for a later point in time. You may have a drug holiday for a year after you have been treated.

Particularly some of within the main agents of Denosumab and Bisphosphonate groups of drugs that would be (inaudible). They all work by slowing down the osteoclasts and stopping the bone breakdown. 

 

Interestingly when you slow down the osteoclast you also slown down the osteoblast so you also slow down the formation. While you're stopping bone loss you do stop new bone forming. So in general they just work to slow down the rate of progression of osteoporosis and won't contribute to bone density necessarily. 

 

When you have got a bone metastasis the osteoclast activity increases and that is to help the bone metastasis (inaudible) to make you more likely to fracture. Any questions?

 

Person #17:  I missed a bit on monitoring the Xgeva?

 

Dr Jane  So the cancer specialists often don't do that sort of monitoring.  Possibly the things they are doing is monitoring the bone density as well but it can slow your bone turning down quite a lot. When you are on Xgeva you are managing your metastases and your dose is much higher and you have to weigh up the benefit of preventing progression of the bone metastases versus you also slow bone turnover down. 

 

So they might say on the balance of  weighing up all those risks you take that as an acceptable risk but there maybe an increase risk of those unusual fractures. Particularly if you are on that sort of treatment maybe for two years.

 

The other thing when you are on those high doses of the Xgeva if you have to have any dental work there is a really high rate of (inaudible) because of your slow bone turnover and bone repair down then when the teeth is taken out and you need to repair the bone underneath. Sometimes they may take a really long time to heal. That is not a reason to not use these agents. If you have had a tooth repaired and it is not healing it is not going to kill you. (inaudible)  We do know that if you are on these agents and you do need to have a tooth repaired that if you go onto antibiotics until it does close over that does help prevent problems with the delayed healing.  It needs a dentist who has some expertise dealing with patients who are on these agents to do the dental extractions and you should just be careful of dental extractions when you are on Xgeva.

 

Person #17:   Are there any sort of guidelines, like people with metastases and PSA comes down therefore it is deemed the cancer is under control, that at that point the Xgeva should be reduced?

 

Dr Jane  I am not aware of a specific written guideline. In general oncologists would either stop your treatment for a period of time or they might reduce the frequency which you have those injections. Instead of having them every month you might go to every two months. You could even go to every six months because the agent Xgeva does last in bones for as much as six months with each injection. 

Person #13:  Could you clarify the comment that you made, the most preference for using Denosumab, Xgeva or Prolia rather than Zometa or one of the other Bisphosphonates.

 

Dr Jane  I think as the evidence has become available about preventing progression on the skeletal metastases, it is thought that there might already be micro metastases that are already present in bone in men with advanced prostate cancer. Therefore these agents may help prevent progression of those metastases in the bone even before they are known. The micro metastases in both breast cancer and prostate cancer (inaudible) bone is (inaudible) by using Donosemad because it has been shown to be more effective. Having said that there is agents like Zometa are very effective for preventing of fracture in osteoporotic men but that completely aside from prostate cancer. If you have significant osteoporosis and currently no evidence of metastasis in bone, it is still a very good agent to use. There is a little bit of evidence that the progression of metastases in bone but not as strong for that as Denosumab. 

There was study that was done specifically using Denosumab in men with advanced prostate cancer to look at fracture prevention. There is (inaudible) that has not been done in a large study in men with prostate cancer for prevention of fracture. Studies of Denosumab state osteoporotic limb however, I can tell you Denosumab does reduce fracture in men and that was regardless of their testosterone levels. 

 

So if you had very low testosterone (inaudible) does prevent fracture and probably as effective as Denosumab and they haven't been compared head to head in that setting? When they were compared head to head it appeared that Denosumab was just a little bit more effective than (inaudible) in preventing of progression of metastases in bone even though they work in a similar way. 

I think they were looking at the first skeletal related events. So in general that would be fracture and it seems to show that compared to using a placebo Zoledronic acid prevented skeletal related events for about 5.6 months better compared to placebo. Denosumab is another 3.6 months advantage over Zoledronic acid. Certainly once you have bone metastasis known Denosumab was shown to be a little bit better than Zoledronic Acid in preventing fracture associated with both osteoporosis and metastases itself.

 

Person #4:  Is Zoledronic Acid, Zometa?

 

Dr Jane   Zometa, that is correct and also Aclasta. When Zoledronic Acid when you used it, it was only available as Zometa. Now it is available as an osteoporosis agent known Aclasta.

Denosumab is available as Xgeva and (inaudible)  that used in osteoporosis and it is also available as an agent called Prolia. It is used as Prolia if you have no known metastasis but it is used as Xgeva where you have a known level of metastasis.

 

Person #3:  What is the newer brand alternative to Zometa, something starting with A?

 

Dr Jane   Aclasta

 

Person #3:  Could I just mention to  Person #13  we have got the information about those clinical trials of Zometa and Xgeva and their comparison on the website.

 

Person #13:  There have been some positives about the beneficial use of Statin in the context of metastatic cancer and not necessarily in the bone. Do you have any comments on that?

 

Dr Jane  The satins is very interesting and in fact they have been known to be used in men to have a beneficial effect on bone density. They do seem to work on the osteoclast. It is probable some of their effects on metastasis they have a similar effect on the osteoclasts to the agents Denosumab and Zoledronic acid. 

Now clearly the doses that are used in general clinical practise have only small effects but they may be beneficial when you look at a large group of men over time who are on these pattern then perhaps have slower progression of metastasis. The effect is certainly going to be weak and the benefit of them as a treating agent is going to be limited by the effect of higher doses they do have toxicity on the muscle.

 

Person #13:  So you would say the use of those in practice would be limited to people with diabetes?

 

Dr Jane  So indications of high cholesterol above a set level, if you have got previous primary disease if you have got diabetes but also for levels there above the recommended levels without those conditions you may also get onto Statin. I would not recommend going out and getting onto Statin.

 

Person #5:  It was mentioned our bones breakdown repair normally. I am just wondering how well bones repair after external beam radiation?

 

Dr Jane  In fact that is a very interesting question. The bone repair is slowed down quite a lot. External beam radiation can be responsible for fractures of itself. It appears to be quite toxic on the osteoblast, the bone formation cells. They use a reduce bone formation in those areas. 

I certainly have a number of patients who after external beam radiation to remote areas of the pelvis who subsequently go on to get fractures in sacrum, lumbar spine and in the pelvis. Because that fall out of radiation having an effect on bone in the external beam scatter. I have seen that more commonly in the women who have had some external beam to the pelvis. I have seen it in men who (inaudible) and they can present often with quite acute pain in the very low back.

 

Person #5:  I have just had some external beam radiation to the T10 in the spine.

 

Dr Jane To treat the metastases itself?  In that context it is a little bit different because the metastasis itself is placing you at very high risk of fracture and if you treat the metastasis you actually potentially reduce the risk of fracture. You can get some vertebral collapse despite the fact that metastasis has been treated and probably because there has been a quite considerable bone loss before the external beam.

 

Person #5:  The radiation also affects the bone marrow there in that area too?

 

Dr Jane  Yes that is correct it does. So all other cell formation but it is increased particularly affect those formations cells and the new cells so the osteoblast and all the red blood cells that are in that particular bone.

 

Person #5:   So virtually it won't repair that at all or would it take years?

 

Dr Jane  That is correct. So often it doesn't repair very well at all and you have got progressive vertebral collapse over time. A lot of the agents you use then to treat bones don't have a lot of effect because you are missing those osteoblast cells in that bone.

 

Person #5:  So you then have to be very careful that you don't jolt the spine in that area?

 

Dr Jane  So in men who have significant osteoporosis my own recommendation and if you have a bone metastases in a vertebra I would suggest no ladders, no step ladders, no climbing up on chairs to do things you shouldn't do. The reason I say that is because the majority of spine related events occur with missing a step. So if you are coming down a ladder and you think you have got the bottom end and you have got one step to go and you get quite a significant vertical jolt if you over balance off a chair then you are much more likely to sustain a fracture in that unstable region of bone. 

You just have to accept to put the ladder out for someone else to take, no more ladders. Step ladders are allowed providing it has a rail that you can hold onto but you must hold onto the rail the reason being you will then use your arms to break the fall and reduce vertical impact.

 

Person #5:  You should still get good exercise to keep muscles etc. nice and strong?

 

Dr Jane  That is a very good point as well. I was going to raise the point of exercise is not so much the effect of exercise itself on bone all though that is part of it. We know that men as they lose their mobility with age you get quite accelerated bone loss that is also important maintaining muscle strength and balance and reduces your risk of fall. 

You're quite elderly in an in a nursing home you're actively arm weight when you are not able to walk reduces your risk of fracture. This probably because just exercising one part of the body helps muscles right throughout the body and it helps with rising reflexes. Having good arm strength is quite important so when you go to fold your arms, reflexes are more quickly when you have good muscle tone in your arms where as if you have very little muscles tone you are much slower to put your arms out break the fall.

 

Chairman Bruce   I would always suggest that somebody who has had bone metastases treated by radiotherapy require to invest in a walking stick at least and use it because that is a constant reminder you have to take a little bit of care.

 

Dr Jane  I see quite a number of people who virtually come to my room looking very unbalanced and I say to them, I don't want to see you coming to my rooms without even a walker. Often you talk to the families they say they are becoming unsteady and quite tired when we go out shopping. Having some sort of support makes quite a lot of difference. 

It does make you more aware of the fact you don't have as good balance and you will take a little bit more care with particularly stairs by making sure you always hold the rail. If you have got a stick and you do get a little unbalanced it is a good reminder and it gives you something to prop yourself up a little bit.  

 

Person #13:   Those of us who are using corticosteroid like Prednisone in conjunction with the newer anti-cancer treatments like Zytiga, I believe there is adverse effect on bone. I was just wondering if there was a balance to be struck as to how much of the so called low dose of Prednisone you use given those two are in conflict to some extent?

 

Dr Jane  Unfortunately Prednisone reduces bone in the same area as where testosterone reduces bone in the spine. Sometimes you have to use two agents beyond the Zytiga for the prostate cancer but you may also need to be on an agent to prevent bone loss from Prednisone. 

 

Prednisone if you are on as much as 7.5mg/day you can automatically go onto the Bisphosphonate class of drugs. If you are on less than 7.5mg it would depend on the presence of osteoporosis and or fracture already. People should be really actively looking for fracture and that is why I mentioned the spine X-ray, to be actively looking to see if there has been some asystematic fractures which would then either qualify you for some tests for either Denosumab or any of the Bisphosphonate. That should probably be done on an annual basis if you are on something like Prednisone as well.

 

Person #13:  I think the standard recommendation with Zytiga is two by 5 mg/day. I think Dr Howard Gurney made a comment in passing a couple of sessions ago that suggests that maybe you have to (inaudible) that a little bit. I think the general comments I have had is that all the trials are done with that combination for hypocalcemia  Ed: [is the presence of low serum calcium levels] and therefore you should use it. I don't see much opinion around about how to optimise the amount or what back up supplementary medication to offset the effect.

 

Dr Jane  It is reasonable to say that agents like Zytiga or Xtandi that use   (inaudible) agents in advanced prostate cancer because they treat the metastases they do reduce fractures.

 

Chairman Bruce   We would like to thank Dr Holmes-Walker for her address. Please know you have given us a lot of information you have answered a lot of question and opened up discussion and I think we are all very grateful. 

 

Dr Jane It has been a pleasure to speak with you all.

 

Chairman Bruce   Now we are back to ordinary business there are a couple of updates from members.

 

Person #11:  Most of you may know I have got a little side-track happening with my side effects of radiation and it is to do with blood in the urine. Last September I started having visual blood in my urine and it continued on. A Cytology test was done and that proved it again. 

I finished up having a Cystoscopy and it diagnosed the Radiation Proctitis in the bladder. Now that diagnosis then lead to me being referred back to radiologist people who then asked me to do a hyperbaric treatment. I could do the hyperbaric treatment where I live up in Townsville, which is what I did.  

The bleeding continued to get worse. I did 50 daily treatments of hyperbaric treatment. For those who are not aware of it the science behind it, it is a chamber they use for divers with decompression problems for the bends. 

 

From a medical point of view they use it for treating diabetics with wounds that are hard to heal, surgery and also radiation problems from people like myself. 

The science quickly is they put you under pressure approximately just over two atmospheres. You are there for two hours. You breathe pure oxygen with a couple of air breaks in between. The idea is under pressure the oxygen is forced to other areas of the body that doesn't see a lot of oxygen just by breathing normal atmospheric air and it helps in the healing process. In my case it works. 

I finished up in Townsville hospital twice in the emergency department late at night with a completely blocked off urethra through blood clots. First time I was in for a couple of days until it cleared up. 

 

The second time I was in for four days before the actual bleeding subsided. I was then given a referral to a urologist and I went and saw him and he explained to me with his interpretation of what he thought may be the problem and he was going to verify that with a cystoscopy the following week.

 

I had the cystoscopy. He went in, and as he thought, the main part of the bleeding was coming from what was left of the prostate gland. I didn't have surgery when I was diagnosed. I just had radiation and ADT so the prostate gland in its form is still there. 

He explained to me in these sorts of cases the interior of the prostate gland is usually filled with a gelatinous type material that continually expands. It has got a lot of blood vessels attached to it plus artery blood feed and it continues to slop off. Although the radiation proctitis is evident in my bladder in the main bleeding part of it is from my prostate. He proceeded to cauterize everything he could find on the outer of the prostate to try and alleviate the bleeding. 

 

It is two weeks down the track now. I have still got problems getting over the treatment. I have a fair bit of pain down there. I have pain urinating but he assures me it will go away in about three weeks. The bleeding has stopped. He said it is still a bit of a wait and see thing and if bleeding occurs in the future then the next step for me maybe to go back in. Under a cystoscopy they may scrape out the entire contents of the prostate and just leave the outer shell and try and get it back to some better cells. 

 

That is where I am at now. On our website there is some information for anyone who may follow me that it is not a nice track at the moment. I was speaking to the radiation oncologist the other day and his comment to me was nearly all my patients go through all their treatment without too much fuss. The 1% of people who tend to have trouble have it all the way along the line and I will see a fair bit of you over the next few years. So that wasn't good to hear. I have just got back two weeks out of this last bit of quarterisation and I will just have to wait and see how it all travels. On the cancer side of it I have been off the ADT since March this year after being on it for two years and my latest PSA level is still at 0.02. It appears I don't have a problem in that respect but I have other problems happening.

 

Person #21:  Will it be your bladder scrapped out not the prostate?

 

Person #11:  No, his advice to me was if this didn't work from the prostate he was going to go in like an orange to get out the gelatinous material right back to get to some good cells around the outside of the casing inside the prostate.

 

Chairman Bruce   You certainly wouldn't want to scrape out the inside of the bladder. Make holes in that and get peritonitis at risk. Whereas in the prostate you have got tissue around it plus a capsule. It is like a subtotal prostatectomy by quartering, except that the prostate is no longer merely prostatic tissue. It is a irradiated prostate and really given a good dose of beam treatment so that it is causing the problems.

 

Person #11:  If anyone out there is having a similar problem I am happy to answer any questions?

 

Person #9  I would like some clarification from  Person #11  and Chairman Bruce about the irradiated prostate. So if someone has under gone the radiation of the prostate as  Person #11  has just done, and I also have under gone that about a year ago. Does that mean the prostate is still there but the cells inside the prostate are no longer functioning and in

    Person #11   case those cells inside the prostate have actually gone gelatinous is my understanding correct?

 

Chairman Bruce   The thing about in radiobiology that there is variable response between person and person. An example of that is say a red haired and dark haired person, Caucasian type, getting a dose of sun. The red head is going to get more burnt than a particular dose of sun compared with the person who has got dark hair. Certainly the person with dark hair has got an olive type skin. That is biological variation. When it gets down to radiotherapy a dose of radiation produces a certain amount of cell kill.

The cancers recovery rate in most cancers that are treated by radiotherapy is slower than the recovery of normal cells. At the end of a course of radiation therapy the normal cells will be reduced to a population from which they may recover or occasionally they may not recover. If they do recover in say an 80% or 75% population compared to what they had to begin with may be less but there is a certain amount of scarring. 

Some people with a real dose of the radiotherapy given, I had 60 gray of radiation. Now they go up to about 75 maybe a little bit more, it will take a bit longer. That there's more confined to the prostate, hence the use of gold grains to be right on target, whereas in my day we purposefully had a centimetre of tissue around the prostate just in case of capsular invasion. When I was treating patients we did that because the surgeons wouldn't touch them except for biopsy. 

There will be occasions when somebody gets a (inaudible) recovery and that is obviously was has happened in  Person #11  case.  Person #11   you do have cells that will allow you to get a healthy layer whereas in the middle your blood vessels are there and are not supported and they tend to bleed. 

 

Person #11:  That is exactly what the urologist said. I received 78 gray of radiation to that organ. I have been advised that there is a percentage of people who have bleeding problems afterwards is very small. Even though it is very small it still exists.

 

Members thank  Person #11  for his contribution today and wish him well.

 

Person #12:  I was diagnosed in 2010. I had radiation past surgery and put on a couple of drugs. At the end of last year I moved to Sydney and I had a really rapid increase in PSA to 87. They put me on chemotherapy for some thirty weeks.  Every three weeks I get chemo. For the first week I am a zombie. It is the same principle as the radiation. 

It was explained to me that the cancer cells don't recover as fast as the good cells. So during the course the chemotherapy knocked down the cancer cells and allows the good cells to recover. So that is for a three weeks cycle for me. The 87 came down after one chemo to 58 and after the second chemo came down to 37. 

So hopefully the progression is good and will continue. It has metastasized into the blood and I have been told if this doesn't works I have got a year and if it does work I might has three or four. Because if is in my blood it can clot and take me out anytime. I am an author and have just completed my first book, D Day Exposed, and about to start my second. That is keeping me occupied. I recommend people to have a hobby, because if you are in total denial then there is a problem. 

I go walking but I might have to cut down on the bike riding after listening to the discussion today. I am lucky enough to be working with an expert team at Concord hospital. I am thankful to Jim_Marshall for all the help he has given me and I wish you the best. I haven't been in contact as I have been very sick for about nine months and I am coming out of that now. I apologise for being rude and not contacting you but I have been concentrating on the treatment.

 

Jim Marshall  No apologies necessary.

 

Person #12:  (Inaudible) because what went onto today was totally new to me. At Concord they all talk to each other. It is a wonderful team I think I am in and lucky to be there and I am lucky to have a wife who organised it all. I feel like I am a lucky person. It is a bit of bad luck what I have got. (Inaudible) I wish you all the best. D Day Exposed is available on the website. I have a second book on the way.

 

Chairman Bruce   Thank you very much Person #12   

Now we will move onto  Person #16  as a co-convenor of the Ipswich Prostate Cancer Support Group. 

 

Person #16:  Since my operation in 2002 I have been dedicated to progressing the group with the co-inaugural convenor. I would like to congratulate all the members in this group. I do not have advanced prostate cancer. I was one of the lucky ones that have been kept at bay. All tests have come back good for the last 12 years. My belief is that the Advanced Prostate Cancer blokes are doing a great deal to give and passing on information to not only the advanced blokes but also to the newly diagnosed blokes. 

We don't know when we are nearly diagnosed if we are actually going to fall into a cure or whether it comes back on you and they have to go onto all these other treatments. At the stage where their PSA starts to rise and their lost. I see it in a lot of our blokes and they are looking for answers. Having the Advanced Prostate Cancer blokes there, in my thinking, is an asset. 

They need that information from these advanced blokes and as well from the other blokes that have localised. They need the extra knowledge so they know if it does come back or if it starts to rise they have information to fall back on. That to me is the whole world. I would like to congratulate everyone, Dr Bruce Kynaston, Jim Marshall and  Euan Perry  and the others I haven't met. Thank you very much.

 

Chairman Bruce  Invites  Person #3   to speak.

 

Person #3:  The main thing I want to mention is I was asked to speak about The Advanced Prostate Cancer Support Group at the Victorian/Tasmanian Conference of PCFA. They had a session on diversity in prostate cancer patients and also support groups that went on for about an hour and fifteen minutes. It was really good exposure for it and got a good response from a lot of the group leaders who it suddenly clicked what we did. 

They all knew about it but not many were referring advanced blokes up to the teleconference and I think we will get more out of it. Listening today and hearing   Person #11  comment about radiologists. I have had stereotactic radiation at Peter MacCallum in Melbourne and that went quite well but after about five or six months I got pain in my groin. Didn't know if this was cancer  recurrence. 

Everyone said no it is not cancer recurrence it is just inflamed muscle from the radiation. It took about four months to actually track down with scans and MRI's and so on that it was actually muscle inflammation. 

The people at Peter Mac were quite surprised. They said out of 100 or so people we have treated with stereotactic radiation you are the first one who has had any side effects like this. 

This gave me great comfort (laughing) and their reaction was, you have got a side effect. 

My oncologist said they are the ones who have done it to you they should fix you up. So with a bit of prodding from the oncologist they then decided they better fix me up. The muscle inflammation problem has now been solved. Hearing the  Person #11   story about it not many people have got problems but if you are the one who have got problems you are going  to have lots of them.

 

Chairman Bruce  why did you have the stereotactic? Was it for the primary prostate or something else?

 

Person #3:  A bit of spot welding for bone mets and lymph nodes mets. The bone was pubic bone and the lymph nodes up near the prostate. Without the report in front of me I can't remember the medical terminology for them.

 

Chairman Bruce  I guess some of your pelvic floor muscles got a blast? If it was muscle that got bothered.

 

Person #3:   It ended up being the adductor abductor area. With steroids and rest and that type of thing, it is starting to come good.

 

Person #13:  So steroids are what they've use to address it?

 

Chairman Bruce   I am pleased you are starting to get some improvement because you didn't sound so good when you started talking about it.

 

Person #3:  The frustration was it just took a while to actually work out what and where it was. In terms of being able to exercise and the groin there are an awful lot of muscles used there. It was something that went on for about four months. Now it is resolving. Thank you to Person #4   for organising an excellent speaker. 

 

Chairman Bruce - Closes Meeting.

 

These Minutes of the Teleconference are general in nature and not meant as advice. You must consult with Health Professionals for advice.