Saturday, 29 October 2011

First randomised trial specifically for aspirin in cancer

Prof. Sir John Burn
Crabsallover has followed the link between taking aspirin and reducation in Cancer since Peter Rothwell research results in 2010.

reposted from:
crabsallover highlightskey pointscomments / links.

Other studies over the past two decades have suggested Aspirin reduced cancer risk, but this was the first randomised control trial, specifically for aspirin in cancer, to prove it.

Aspirin cuts the risk of bowel cancer in people with inherited susceptibility to the disease,The Guardian has today reported. The newspaper said that a study of long-term aspirin use found it cut the risk of bowel cancer by more than 60% in these individuals.

Prof Sir John Burns (wikipedia) (won a Knighthood 2009) from Newcastle Uni (full list of John Burn publications) on the Today programme (2 min interview with Evan Davis) said 

 Burns mentioned very good research of Peter Rothwell looking at effect on aspirin on heart attack trials. Burns trial results:Out of 250 in trial group 23 cancers occurred in the placebo group but only 10 in the aspirin group.  63% fewer cancers!  In some way aspirin knocks off the cells that are going to be cancerous in a few years time. One theory is that inflammation is involved in cancer progression, aspirins inhibit prostaglandin production. John Burns personal theory is that it is driving programmed cell death (apoptosis). Plants make salicylates (cf aspirin is a salicylate derived from white willow bark) which drive programmed cell death and protects the bark from infection.

Prof Sir John Burn, from Newcastle University, said there were 30,000 adults in the UK with Lynch syndrome.
If all were given the treatment he said it would prevent 10,000 cancers over 30 years and he speculated that this could possibly prevent 1,000 deaths from the disease.
However, there would also be side effects.
"If we can prevent 10,000 cancers in return for 1,000 ulcers and 100 strokes, in most people's minds that's a good deal," he said.
"People who've got a clear family history of, particularly, bowel cancer should seriously consider adding low dose aspirin to their routine and particularly those people who've got a genetic predisposition."

One of the questions asked by the research into aspirin was whether healthy people with no family risks should take the drug.
The lower the risk of heart attack or cancer, the lower the benefit of taking aspirin, yet there are still potentially deadly side effects.
Sir John said that it was a "finely balanced argument" and that he decided the risks were worth it for him.
"I think where we're headed for is people that are in their 50s and 60s would look very seriously at adding a low dose aspirin to their daily routine because it's giving protection against cancer, heart attack and stroke.
"But if they do that they've got to have their eyes wide open. They will increase their risk of ulcers and gastrointestinal bleeds and very rarely they will have a stroke caused by the aspirin."

View John Burns interviewed by Dominic Hughes, BBC

Fergus Walsh, BBC Health Correspondent,  reports having taken aspirin daily for 11 months since the Peter Rothwell trial results.

Those on the John Burn trial took 600mg aspirin daily which is a much bigger dose than the 75 mg that many middle-aged people like me take to reduce their risk of cardiovascular disease. I wrote last year: "If I get an intestinal bleed in a few months time and am taken to hospital needing a blood transfusion, then it will be easy to argue that I got it wrong."
Well, so far so good.
John Burn also looked at other cancers eg womb and found a 50% reduction (Telegraph interview)

John Burn explains his trials and the biochemistry (8min 20s) of Aspirin mechanism to prevent cancers. It might be making faulty cells fall on their sword.

100,000 years ago we used to forage on plants that used salicylates to defend themselves. Now our diet is free of salicyates. Above paper in picture is

J. Burn, P. D. Chapman, D. T. Bishop and J. Mathers (1998). Diet and cancer prevention: the Concerted Action Polyp Prevention (CAPP) Studies. Proceedings of the Nutrition Society, 57 , pp 183-186 doi:10.1079/PNS19980030 (full pdf) 

Another 10 min video on mechanism of action of aspirin (technical)

another presentation by John Burn - trial results and biochem (5min 50s) "as in plants, salicylates initiate apoptosis (programmed cell death) among genetically abnormal stem cells that have yet to become cancer."

By: Johnson, A. S.; Arthur, H. M.; Burn, J.; Wilson, R. G.. Gut, Apr2004 Supplement 3, Vol. 53, pA21-A21, 
Conclusion: Both aspirin and celecoxib caused dose dependent reduction in cell viability, proliferation, and angiogenesis. Celecoxib produced these effects at levels in excess of normal serum levels when it is no longer COX-2 selective. Aspirin induces apoptosis via a COX-2 independent mechanism which may facilitate angiogenesis arrest and play a critical role in limiting tumour growth.

The Lancet Podcast of the 28th October 2011 press conference (20mins) - John Burn & Tim Bishop

taking 600mg / day aspirin gives 60% prevention of cancer - 75mg gives 25% prevention (13 mins) .. but a low dose will avoid a lot of ulcers.. (14 mins).. CaPP3 trials will give clue to best dose 75mg / 300mg / 600mg per day to offset cancer. CaPP3 website now launched!
 Press Release embargo 28th October 2011

The Lancet comments (subscription required)
'The long-term results of CAPP2 are also invaluable for the continued assessment of aspirin for prevention of sporadic colorectal cancer, which is not currently recommended mainly because of concerns about toxic effects and continuing uncertainty about dose and duration.10 With aspirin's well established vascular benefits and recent evidence of benefit for colorectal and other cancers in pooled cardiovascular randomised trials,11 Burn and colleagues' findings might at last tip the scales in favour of aspirin as the chemopreventive agent of choice for many individuals.

Does this long-term follow-up analysis allow a definitive conclusion, say for standard regulatory approval, about aspirin's ability to prevent colorectal cancer? In isolation, no, since the results of the primary analysis were not significant for the ITT (Intention-To-Treat) population. The data strongly support routine use of aspirin, however, for patients with Lynch syndrome as an adjunct to intensive cancer surveillance. As the first randomised trial of aspirin with colorectal cancer as the primary endpoint, CAPP2 also certainly moves us closer to a more definitive answer on aspirin's overall role in the prevention of colorectal cancer. Unfortunately, prohibitive logistics make a randomised trial of aspirin prevention with a colorectal cancer endpoint in a sporadic-risk population unlikely. Therefore, these results from CAPP2 and previous evidence arguably support more general recommendations to consider aspirin for prevention of colorectal cancer in the context of individualised risk-benefit assessments.

Cancer Research UK comment 'People with Lynch syndrome are about 10 times more likely that the general population to develop cancer, particularly of the bowel and womb, and often at a young age.'

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