Does anyone know if protocols at certain institutions include use of radiosensitizing agents in salvage therapy, or are these just at the research stage?
Radiosensitizers: Does anyone know if... - Advanced Prostate...
Radiosensitizers
Written by
Spaceman210
To view profiles and participate in discussions please or .
Read more about...
16 Replies
•
In this country, these treatments are limited to clinical trials.. In Germany it would seem they are in general use and they are available in other countries as well..Here, it's more important to get the patents bought up so Big Pharma can call the shots..
Thanks - fascinating.
Here's another take on that.
Big Pharma would much rather be able to introduce their drugs without going through clinical trials. It would save them a huge amount of money and enable them to start charging for the drugs right away without waiting for approval. However, the FDA wants evidence that drugs are safe and actually work before they allow companies to sell them to the general public.
I'm not a big fan of big pharma, but I am a big fan of the FDA. There is somewhat less independence at the FDA than I'd like, but more than we might expect given the financial and lobbying pressures that big pharma can exert. Most countries don't even try to test drugs. They rely on our U.S. FDA to do it.
Alan
Do you really believe that big pharma does not have the political influence to get rid of those expensive trials? With the revolving door of big pharma executives and FDA boards they pretty much run the place. Those expensive trials are there to protect their profits not to protect the public. Those trials prevent some start up research company from come up with cheaper better working drugs.
I agree that big pharma has one of the most powerful lobbies in the U.S., maybe the most powerful. But the FDA was created before big pharma really existed and I'm hopeful that pharma can't abolish it. The people still have some shreds of power in our democracy. As for start up research companies, big pharma and startups work together. The great hope of each of the startups is to discover some terrific drug and sell it and themselves to a big pharma. That's how they make their money and big pharma likes it that way because it gives them opportunities to own drugs without spending money on research. Most big pharma has greatly reduced their research budgets.
Alan
What you want ideally is something that sensitizes the cancer, but not healthy tissue to the effects of radiation. If you radiosensitize healthy tissue, you just get more side effects. The best strategy is to deliver the highest radiation dose that is safe (given the precision of the equipment). At MSK and UCLA, they are routinely delivering 72 Gy to the prostate bed:
pcnrv.blogspot.com/2016/11/...
However, others are more conservative. It's a good discussion to have with your RO.
The single best thing you can do to radiosensitize the cancer and radioprotect healthy tissue is exercise. One of the ways cancer cells avoid radiation damage is through hypoxia (reduced blood oxygenation). Exercise delivers oxygen to cells. in cancer cells, the oxygen combines with the radiation to form free radicals that irreversibly destroys their DNA. In healthy cells, the increased blood flow makes them healthier and less prone to destruction. A win-win! When I had my radiation, I increased my cardio workouts to an hour every morning before my radiation treatment.
Hyperthermia has been suggested as radiosensitizing and there is a clinical trial in Germany for this:
pcnrv.blogspot.com/2018/01/...
Supplements MAY play a role, but one has to be very careful to avoid antioxidants and free radical absorbers, as they may do the opposite. Among the radiosensitizing supplements/drugs that MAY be useful and are probably safe to take during treatment are statins, metformin, aspirin/NSAIDs, and soy isoflavones. This is all based on lab studies, not clinical trials. There are others (like modified citrus pectin and resveratrol) where the evidence is even weaker, and no safety studies have been done.
Thanks a lot - great info! Yes, I am aware of the concern for antioxidants. I've also seen references to curcumin, berberine, blueberry being claimed to have radiosensitizing effects, but not trials for such.
Yes, they've all been examined in lab studies. The problem with curcumin (and several other supplements) is that in humans, not enough of it makes it to the cancer to have any effect. They are working at chemically manipulating the molecule to get it past liver metabolism. I've seen the studies for berberine, but because it hasn't been clinically tested, we have no idea (1) if it radiosensitizes in real live humans or (2) if it radiosensitizes healthy cells as well (which would increase toxicity). Nothing wrong with eating lots of blueberries, but I would avoid it as a supplement because of the antioxidant problem.
I often wonder if any of these oral supplements have been investigated in suppository form for absorption.
The problem isn't so much getting through the intestines (although that is a major part of the problem for some supplements), as first pass liver metabolism. Enzymes in the liver (and other organs) are activated very quickly when foreign chemicals enter circulation. It is their job to detoxify what it perceives as toxins. For example, 90% of the curcumin that does make it past the gut is metabolized in 30 minutes - far too brief to have ANY biological effect.
ncbi.nlm.nih.gov/pubmed/696...
I pointed to curcumin, but a similar fate awaits most supplements - they become expensive urine and feces very quickly. That's why these lab studies using mice and rats are almost useless - they don't describe the pharmacodynamics of human systems.
I see - thanks
If a man has standard EBRT for Pca in his PG it often consists of 35 RT sessions over 5 weeks, 5 days a week, with beams in 4 directions in a cross pattern so that that where the 4 beams intersect, is a volume containing the dimensions of the PG and all cells within the "target volume" which may be as big as a golf ball get an accumulated total average of 70Grey of Xrays. The four input paths of beams have a lesser amount of Greys which are considered to be below the levels that would affect healthy tissue badly. I had this type of EBRT for my primary form of treatment. The horizontal input beams paths are through my hip bones and vertical beams through my rectum, and I had side effects of bleeding rectum 18 mths later, and worsened bowel function, but now, some 8 years later, I am OK, even after getting an extra 31Grey of IMRT 2 years ago via Calyspso method using 4 alternative pathway directions. That caused 2 months of severe radiation collitis despite the use of hydrogel to limit futher damage to rectum. This extra IMRT in 2016 was called salvation EBRT which raised the total amount to PG to 101 Grey. But there are other ways to get more RT to the PG, notably bt brachytherapy and added EBRT and 150Grey is not unheard of. The more RT to PG, the more likely you are to have problems of incontinence. I am OK with both feacal and urinary continence, but all sex ability or pleasure from Rodger is entirely exterminated, and especially after 8 years of ADT.
So, what happened to my Pca at PG? Well, before the 2016 extra RT to PG, a PsMa gallium scan had just become available in Melbourne, and I had one, and it showed PG was enlarged, full of Pca, but not spread locally, but was a big danger that it might, hence my acceptance of the extra 31Gy. I had two upper thorax lymph nodes show positive, and they were also radiated with PG.
I was told thr extra RT would kill all Pca in PG.
But in 2017 and 2018 I have had 3 more PsMa Ga68 scans, and they have all shown PsMa avidity remaining in PG, so the extra 31Gy did not kill the remaining Pca in PG. But it had not spread locally, and in last PsMa scan after 5 chemo shots it was confined to a central portion of PG.
Meanwhile, since 2016, more lymph nodes showed mets and countless bone mets showed up. Yesterday I had my first Lu177 infusion because it is the bone mets that are my biggest threat to my QOL. The 5 chemo shots had not worked because Psa went from 12 to 40+ and not DOWN which might have indicated it was worth continuing.
I have been told the Lu177 is my only hope, the Atomic Solution, by means of dropping minni atom bombs at each site where a tumour is located and letting alpha particles do their damage to cancer cells, and to an unknown amount of healthy cells. Radiation sensitivity of any man's Pca can vary enormously, and some men told me they had Psa go to 5+ and a Gleason 5 or 6 tumour was found, and they had the same treatment I had and 10 years later their Psa is not measurable and they did not need ADT. They had a weak form of Pca; mine was described as young man's type and agressive.
But I read elesewhere that those with Gleason score of 9+ had only 10% success rate for standard EBRT. That seemed true in my case. BUT, before I had the ADT and the RT, the Pca had probably spread to many sites including my bones, and the ADT suppressed their growth as it did for PG until 2016 when it began to fail as it always does. So without supression, the mets became big enough to show up in PsMa Ga scans. I had Cosadex and Zytiga which supressed a bit for 18 months until I needed to go to chemo, or whatever else was available, or just die soon. This suprised doctors who thought I had no spread; and its the spread that kills.
But the PsMa Ga scans upset a lot of men when it became available because it meant that no man could ever assume he had no mets even though PsMa Ga scan did not show them while Psa remained below say 2.0. So the more sensitive the scans become, the more likely it is that initial RP and RT is not enough to get an escape from death years later from Pca, after a long and expensive battle.
sensitizing Pca to make RT of any kind work better is a kind of uncertain science on which no reliance might be made. EBRT or IMRT of any kind is only potentially good for large targets and is no good where a man has countless mets. And it seems all RT will affect some Pca cells, but perhaps never all of them, and so resistance to any further RT can increase and finding ways to make these hardy Pca cells more likely to secumb of chemo or more RT is a very unknown science.
It has been suggested the ADT makes Pca "weaker" and more likely to be zapped by RT of any kind, and I was told this before having the RT, and I had 6 months of ADT before the EBRT but mainly to shrink the size of PG tumour so beam size could be reduced to keep damage to healthy tissues to a minimum.
This idea did not seem true for me because after 2 years of ADT and 18 months after the EBRT, I ceased all ADT and Psa went from 0.08 to 8.0 in 6 months, and maybe that's when Pca spread to bones et all. Nobody knew when my spread occurred, but it may have been over different periods.
Whether LU177 works cannot be known for at least a month, when I expect my Psa to fall below 40. It usually takes some time to work on bone mets which are PsMa avid, and it seems mine are, and if this was not the case, Lu177 would be useless for bone mets, and i'd need Ra223. Actinium 225 is said to be the new interesting nucliede but the doc giving me the Lu177 said Ac225 has far worse side effects, so its better to pursure a slower fix with Lu177.
Big Pharma is unfortunately discredited for possible atrocious ethics, but FDA is not going to be abolished soon it seems. Who else is to make anything to cure Pca?
Immune therapy looks promising, but so far, there is little available therapy anywhere, despite press reports of huge progress. Success rates for Provenge are dismal, and so far Marsden Hospital in UK gives improvement to men's lives in only 15 % of cases, so whatever they might offer may never be approved because success rates are not at least 50%. Immune therapy can be difficult to perfect because altered white cells may attack healthy tissues, or the cancer might mutate so much so soon that the altered white cells can only kill cells that have not mutated; but its an uncertain science, because so far, Marsden have said when their IT works it is in cases where men have not had a benefit from ADT or RT and there has been much mutation.
But what I report about Marsden is months old, and I am not completely up to date, but there is NO IT available in Oz yet. Much expensive research is being done, and if a fix for Pca is found, it may be possible for many other cancers so the $$$ reward for these companies if they succeed first with a patented fix is huge. But research cost is high; one guy or gal in a white coat in a lab might cost
$500k per year, and a team of 10 might cost $5million.
For any benefit to the public, the public must allow the companies to make a profit and be prepared to pay a lot to live longer.
Patrick Turner.
Are you talking about things like LU-177 and Radium 223 ?
I don't know but referring to whatever concurrently administered agents may increase radiation effectiveness.
May want to look into fasting prior to treatment. There is some interesting research on this. lookup utube or netflix, "science of fasting".
Thanks!
