Zie ook literatuurlijst specifiek bij darmkanker , waaronder preventiestudies van arts-bioloog drs. Engelbert Valstar

7 januari 2019: Bron: The Lancet

Aspirine heeft in enkele kleinere postpectieve studies wel bewezen darmkanker te kunnen voorkomen, al hoewel daar ook studies tegenover staan die dit niet aantonen. Ook Omega-3 vetzuren - EPA = eicosapentaenoic acid blijkt uit studies kanker te kunnen voorkomen. Beide producten met weinig bijwerkingen en risico al zijn de risico's bij aspirine wel groter dan bij EPA. (zie in gerelateerde artikelen).

Afbeeldingsresultaat voor image of EPA - eicosapentaenoic acid

Nu blijkt uit een grote gerandomiseerde placebo gecontroleerde studie bij 709 patienten totaal dat er geen enkele verschil zit in het ontwikkelen van darmpoliepen (adenomen), die vaak voorlopers zijn van adenocarcinomen / darmkanker tussen zowel aspirine en EPA alleen gegeven of ook samen in vergelijking met een placebo. 

Uit vier groepen  kwamen deze resultaten na vijf jaar bij totaal 709 deelnemers in de periode vanaf 11 November, 2011, en 10 juni 2016:

Adenomen (ADR) traden op bij:

  • 61% (100 uit 163) in de placebo groep,
  • 63% (97 uit 153) in de EPA groep,
  • 61% (100 uit 163) in de aspirine groep, 
  • 61% (98 of 161) in de EPA plus aspirine groep,

met dus geen bewijs van enig effect voor EPA (risk ratio 0·98, 95% CI 0·87 to 1·12; risk difference -0·9%, -8·8 to 6·9; p=0·81) of aspirine (RR 0·99 (0·87 to 1·12; risk difference -0·6%, -8·5 to 7·2; p=0·88).

Zie onderstaande grafiek voor alle karakteristieken

Table 1Baseline characteristics
Placebo (n=176)EPA (n=178)Aspirin (n=176)EPA plus aspirin (n=177)Total (n=707)
Age (years) 65 (62–69) 65 (62–69) 65 (62–69) 66 (62–69) 65 (62–69)
Sex
Male 139 (79%) 138 (78%) 140 (80%) 146 (82%) 563 (80%)
Female 37 (21%) 40 (22%) 36 (20%) 31 (18%) 144 (20%)
Excess bodyweight
As per WHO guidelines, BMI is measured as kg/m2.
Overweight (BMI 25–29·9) 76 (43%) 77 (43%) 81 (46%) 77 (44%) 311 (44%)
Obese (BMI ≥30) 68 (39%) 70 (39%) 71 (40%) 61 (34%) 270 (38%)
History of diabetes 24 (14%) 24 (13%) 18 (10%) 15 (8%) 81 (11%)
Cigarette smoking
Current smoker 34 (19%) 13 (7%) 27 (15%) 32 (18%) 106 (15%)
Previous smoker 82 (47%) 96 (54%) 89 (51%) 80 (45%) 347 (49%)
Never smoked 60 (34%) 69 (39%) 60 (34%) 65 (37%) 254 (36%)
Regular medication 81 (46%) 93 (52%) 88 (50%) 92 (52%) 354 (50%)
Medication before trial entry
Not mutually exclusive, some participants reported more than one category.
Statin 50 (28%) 54 (30%) 51 (29%) 55 (31%) 210 (30%)
Calcium 1 (1%) 3 (2%) 3 (2%) 0 7 (1%)
Calcium plus vitamin D 2 (1%) 1 (<1%) 4 (2%) 4 (2%) 11 (2%)
Metformin 14 (8%) 12 (7%) 11 (6%) 9 (5%) 46 (7%)
Glitazone 1 (<1%) 1 (<1%) 1 (<1%) 0 3 (<1%)
Proton-pump inhibitor 19 (11%) 27 (15%) 24 (14%) 20 (11%) 90 (13%)
Aspirin 0 0 0 1 (<1%) 1 (<1%)
Fish oil 1 (1%) 4 (2%) 2 (1%) 2 (1%) 9 (1%)
Non-aspirin NSAID 1 (1%) 4 (2%) 1 (<1%) 5 (3%) 11 (2%)
Other 34 (19%) 34 (19%) 37 (21%) 48 (27%) 153 (22%)
Colorectal adenoma characteristics
Total number of adenomas 856 892 927 856 3531
Number of adenomas per participant 4·9 (2·6) 5·0 (2·2) 5·3 (2·7) 4·8 (2·3) 5·0 (2·5)
Number of advanced
Diameter of at least 10 mm, high-grade dysplasia, or tubulovillous or villous histology.
adenomas per participant
1·2 (0·9) 1·3 (1·0) 1·2 (0·9) 1·1 (0·9) 1·2 (0·9)
≥1 adenoma proximal to splenic flexure 141 (80%) 146 (82%) 153 (87%) 144 (81%) 584 (83%)
Histological type
Colorectal adenoma-level data.
Conventional 812/856 (95%) 844/892 (95%) 895/927 (97%) 809/856 (95%) 3360 (95%)
Tubular or tubulovillous 807/856 (94%) 834/892 (93%) 885/927 (95%) 803/856 (94%) 3329 (94%)
Villous 5/856 (1%) 10/892 (1%) 10/927 (1%) 6/856 (<1%) 31 (1%)
Serrated 22/856 (3%) 30/892 (3%) 18/927 (2%) 21/856 (2%) 91 (3%)
Not sent to pathology 18/856 (2%) 16/892 (2%) 13/927 (2%) 21/856 (2%) 68 (2%)
Missing data 4/856 (<1%) 2/892 (<1%) 1/927 (<1%) 5/856 (1%) 12 (<1%)
Repeat screening endoscopy
No 136 (77%) 128 (72%) 133 (76%) 133 (75%) 530 (75%)
Yes 25 (14%) 33 (19%) 24 (14%) 34 (19%) 116 (16%)
Missing 15 (9%) 17 (10%) 19 (11%) 10 (6%) 61 (9%)
One participant in the EPA group and one in the aspirin group withdrew from the study immediately after providing consent and so their data are not reported here. Data are median (IQR), n (%), or mean (SD). BMI=body-mass index. EPA=eicosapentaenoic acid. NSAID=non-steroidal anti-inflammatory drug.
* As per WHO guidelines, BMI is measured as kg/m2.
Not mutually exclusive, some participants reported more than one category.
Diameter of at least 10 mm, high-grade dysplasia, or tubulovillous or villous histology.
§ Colorectal adenoma-level data.

Het volledige studierapport: 

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial is gratis in te zien.

Hier het abstract van de studie plus referentielijst:

Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence.

Articles| Volume 392, ISSUE 10164, P2583-2594, December 15, 2018

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial

Open AccessPublished:November 19, 2018DOI:https://doi.org/10.1016/S0140-6736(18)31775-6

Summary

Background

The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy.

Methods

In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55–73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847.

Findings

Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio 0·98, 95% CI 0·87 to 1·12; risk difference −0·9%, −8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference −0·6%, −8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group).

Interpretation

Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence.

Funding

Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.

References

  • Cancer Research UK
Cancer statistics for the UK.
  • Logan RF
  • Patnick J
  • Nickerson C
  • Coleman L
  • Rutter MD
  • von Wagner C
Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests.
Gut. 2012; 61: 1439-1446
  • Gill MD
  • Bramble MG
  • Rees CJ
  • Lee TJW
  • Bradburn DM
  • Mills SJ
Comparison of screen-detected and interval colorectal cancers in the Bowel Cancer Screening Programme.
Br J Cancer. 2012; 107: 417-421
  • Robertson DJ
  • Greenberg ER
  • Beach M
  • et al.
Colorectal cancer in patients under close colonoscopic surveillance.
Gastroenterology. 2005; 129: 34-41
  • Strum WB
Colorectal adenomas.
N Engl J Med. 2016; 374: 1065-1075
  • Zauber AG
  • Winawer SJ
  • O'Brien MJ
  • et al.
Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.
N Engl J Med. 2012; 366: 687-696
  • Lee MS
  • Menter DG
  • Kopetz S
Right versus left colon cancer biology: integrating the consensus molecular subtypes.
J Natl Compr Canc Netw. 2017; 15: 411-419
  • East JE
  • Vieth M
  • Rex DK
Serrated lesions in colorectal cancer screening: detection, resection, pathology and surveillance.
Gut. 2015; 64: 991-1000
  • Grady WM
  • Markowitz SD
The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening.
Dig Dis Sci. 2015; 60: 762-772
  • West NJ
  • Clark SK
  • Phillips RK
  • et al.
Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis.
Gut. 2010; 59: 918-925
  • Siscovick DS
  • Barringer TA
  • Fretts AM
  • et al.
Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease. A science advisory from the American Heart Association.
Circulation. 2017; 135: e867-e884
  • Cole BF
  • Logan RF
  • Halabi S
  • et al.
Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials.
J Natl Cancer Inst. 2009; 101: 256-266
  • Rothwell PM
  • Wilson M
  • Elwin CE
  • et al.
Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials.
Lancet. 2010; 376: 1741-1750
  • Cuzick J
  • Thorat MA
  • Bosetti C
  • et al.
Estimates of benefits and harms of prophylactic use of aspirin in the general population.
Ann Oncol. 2015; 26: 47-57
  • Higurashi T
  • Hosono K
  • Takahashi H
  • et al.
Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial.
Lancet Oncol. 2016; 17: 475-483
  • Benamouzig R
  • Deyra J
  • Martin A
  • et al.
Daily soluble aspirin and prevention of colorectal adenoma recurrence: one year results of the APACC trial.
Gastroenterology. 2003; 125: 328-336
  • Hull MA
  • Sandell AC
  • Montgomery AA
  • et al.
A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial.
Trials. 2013; 14: 237
  • Volpato M
  • Spencer JA
  • Race AD
  • et al.
A liquid chromatography-tandem mass spectrometry method to measure fatty acids in biological samples.
J Chromatogr B Analyt Technol Biomed Life Sci. 2017; 1055–56: 125-134
  • Loughrey MB
  • Shepherd NA
The pathology of bowel cancer screening.
Histopathology. 2015; 66: 66-77
  • Montgomery AA
  • Peters TJ
  • Little P
Design, analysis and presentation of factorial randomised controlled trials.
BMC Med Res Methodol. 2003; 3: 26
  • Lee TJ
  • Nickerson C
  • Goddard AF
  • Rees CJ
  • McNally RJ
  • Rutter MD
Outcome of 12-month surveillance colonoscopy in high-risk patients in the National Health Service Bowel Cancer Screening Programme.
Colorectal Dis. 2013; 15: e435-e442
  • Lee TJ
  • Rutter MD
  • Blanks RG
  • et al.
Colonoscopy quality measures: experience from the NHS Bowel Cancer Screening Programme.
Gut. 2012; 61: 1050-1057
  • Loberg M
  • Kalager M
  • Holme O
  • Hoff G
  • Adami HO
  • Bretthauer M
Long-term colorectal-cancer mortality after adenoma removal.
N Engl J Med. 2014; 371: 799-807
  • Sandler RS
  • Halabi S
  • Baron JA
  • et al.
A Randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer.
N Engl J Med. 2003; 348: 883-890
  • Logan RF
  • Grainge MJ
  • Shepherd VC
  • Armitage NC
  • Muir KR
Aspirin and folic acid for the prevention of recurrent colorectal adenomas.
Gastroenterology. 2008; 134: 29-38
  • Wallace K
  • Grau MV
  • Ahnen D
  • et al.
The association of lifestyle and dietary factors with the risk for serrated polyps of the colorectum.
Cancer Epidemiol Biomarkers Prev. 2009; 18: 2310-2317
  • Bailie L
  • Loughrey MB
  • Coleman HG
Lifestyle risk factors for serrated colorectal polyps: a systematic review and meta-analysis.
Gastroenterology. 2017; 152: 92-104
  • Schuchardt JP
  • Hahn A
Bioavailability of long-chain omega-3 fatty acids.
Prostaglandins Leukot Essent Fatty Acids. 2013; 89: 1-8
  • Stark KD
  • Van Elswyk ME
  • Higgins MR
  • Weatherford CA
  • Salem N
Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults.
Prog Lipid Res. 2016; 63: 132-152
  • Watson H
  • Cockbain AJ
  • Spencer J
  • et al.
Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases.
Prostaglandins Leukot Essent Fatty Acids. 2016; 115: 60-66

Plaats een reactie ...

5 Reacties op "Aspirine noch EPA (omega-3 polyunsaturated fatty acid eicosapentaenoic acid) noch samen voorkomt ontstaan van darmpoliepen (adenomen) in vergelijking met placebo"

  • e.valstar :
    Het getal 10 heb ik van elders en is een schatting, die ik denk aan de hoge kant is. De onderzoekers hebben het niet over carcinomen. Terecht omdat daar verder vanwege de lage aantallen sowieso geen conclusie aan te verbinden is. Iets wat terecht is mede gezien mijn getalsmatige uitleg. Punt is dat adenoomfrequentie weinig zegt. Ik kan voorbeelden geven van stoffen die premaligne veranderingen tegen gaan, maar de kans op darmkanker niet verminderen (foliumzuur), maar ook van stoffen die de adenoomfrequentie niet direkt verminderen (oa dit onderzoek), maar de kans op darmkanker bij langdurige inname wel verminderen (aspirine). Feit blijft dat kritisch nadenken uiterst relevant is. Iets waar veel homeopaten en VtdK-scribenten niet sterk in zijn.
  • e.valstar :
    Kees het onderzoek gaat over adenomen en dat zijn goedaardige tumoren; dus geen adenocarcinomen. Het getal 10 met betrekking tot carcinomen heb ik ergens gelezen. Klopt dat getal dan blijft mijn getalsmatige interpretatie staan. Maar let op jij moet in je Nederlandse deel adenocarcinomen vervangen door adenomen en zeggen dat dit goedaardige tumoren zijn.
  • Kees :
    Engelberg, Heb je dit onderzoek wel echt gelezen? Het onderzoek gaat over drie jaar. Over vier groepen verdeeld waren er 709 deelnemers. In elke groep kwamen rond de 100 (62 procent) adenocarcinomen voor dus 10x zoveel als jij noemt.

    Dit lezende geldt dan nog steeds je kritiek?

    Kees, webmaster
  • e.valstar :
    Extra nog meer specifieke kritiek is dat aspirine en dat geldt voor meer variabelen bij darmkanker sowieso pas een effect bij veel langere inname dan 1 jaar laat zien. De onderzoekers hebben van te voren niet goed nagedacht, wat bij een experiment toch echt nodig is.
  • e.valstar :
    Dit onderzoek is slecht niet door de principiele opzet, maar door de geringe statistische power. In elke groep zitten iets van 10 carcinomen. Volgens de poissonverdeling is de standaardfout van 10 gebeurtenissen (ik heb het over de carcinomen) de wortel uit dat getal. Significantie ligt dus bij 2 keer die wortel. 10 heeft dus een onzekerheid van plus/min 6,3, afgerond 7. Dit betekent dat een effect van 50% niet eens is vast te stellen. De groep had groter gemoeten en de follow-up langer. Dit onderzoek kan in de prullkenbak.

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