Abstract

There is a growing body of evidence that aspirin could be helpful in the treatment of cancer.  In this paper, ten randomised controlled trials are reviewed covering more than 8,000 patients with several different forms of the disease.  It appears that aspirin is well tolerated and the evidence of benefit from aspirin is suggestive if not conclusive.  Yet there are limitations to the randomised controlled trials, for example they exclude many forms of the disease.  This includes solid cancers such as pancreatic or brain as well as certain bone and blood cancers.  Plus, they only explore the potential of aspirin alongside current best treatments which does not represent cancer patients who either decline or cannot access treatments.  The latter maybe particularly relevant to developing countries.  Furthermore, the trials are also only focussed on adults and perhaps aspirin trials might be considered in younger patients with cancer.  The overall take away messages are that adult cancer patients should be informed of the current evidence.  Clinical audits of aspirin use in cancer patients now seem warranted to understand their current aspirin use and clarify the potential for further studies.  The practice of de-prescribing aspirin in some advanced cancer patients also needs a further review.          

Key words : aspirin, cancer, treatment

Dr Gareth P. Morgan, FRSPH.

Secretary of the Welsh Aspirin Group.

Address for correspondence : morganfforrdbeck@gmail.com

Submission made on behalf of the Welsh Aspirin Group.

Introduction : Aspirin is an easily available and low-cost medicine, with a number of therapeutic uses.  The first trial of aspirin in the treatment of vascular disease was published over 50 years ago in the 1970’s (1) with systematic reviews following in 1994 (2) and 2002 (3).  Low-dose aspirin, 75-150 mg per day, is widely used to treat patients with vascular disease and is still an important medicine in 21^st century healthcare. Further, aspirin may also be combined with other treatments as a polypill (4). 

Another potentially important role for aspirin is in the preservation of good health as part of ageing.  In 2005, two articles were published and these debated the potential of aspirin to be taken at the 50 years of age as part of healthy ageing (5,6).  There is evidence that aspirin could help to reduce colorectal cancer risk and the benefit versus risk balance of taking aspirin at 50 may be favourable.  It might be timely to revisit this debate and at least consider aspirin being a part of the colorectal cancer screening programmes that often start at 50 years old.  Australia is exploring effective implementation strategies for aspirin (7) thus highlighting the far-reaching public health potential of the medicine.

As well as the above, aspirin is also now undergoing serious consideration as a treatment for cancer.  This is not a new situation as the therapeutic potential of aspirin as a cancer treatment was reported in the last century (8).  Since then, further evidence to support the suggestion that aspirin has a favourable benefit versus risk balance in the treatment of cancer has emerged.  This includes evidence on mechanism of action (9), a meta-analysis of observational studies (10) and post-hoc follow up of cancer outcomes from trials of aspirin in vascular disease (11).  Yet, each of the sources – whilst individually and collectively highly suggestive – has limitations.  Pharmacological mechanisms of action of aspirin provide plausibility yet of themselves do not offer guarantees of benefit.  Observational studies suffer from limitation of bias, chance and confounding that cannot be eliminated.  Finally, post-hoc analysis can generate or even support a hypothesis rather than test and refute or confirm them.

There are other arguments that can be presented to support adult patients with a cancer diagnosis, as well as their family members or carers, now being informed about aspirin as an additional treatment option.  This includes the relative safety of the medicine (12), especially in comparison to other cancer treatments which often have unpleasant side effects.  Other arguments include the ethical considerations of allowing patients to make informed choices (13) as well as a health economic case (14).  Yet, there are still ad hoc randomised controlled trials ongoing for aspirin and cancer treatment and a valid position is to wait for these to report.  This paper summarises current evidence.

Methods : Trials were identified using a number of methods.  The search strategy of randomised controlled trials using key words including ‘aspirin, cancer and trials’ have been performed previously to 2020 using Medline as an engine and was reported in earlier work (10).  These searches have been reviewed again and only ad hoc trials – that is trials specifically set up to test the effect of aspirin in cancer treatment – were included in the analysis.  Therefore, any observational study or other forms of evidence was omitted from this specific investigation with a tight inclusion criterion on ad hoc trials.

Since 2020, an ongoing monitoring of published ad hoc randomised controlled trials on aspirin and cancer treatment was undertaken.  This has included continued searches on Medline as well as looking at website or newspaper reports, conference abstracts plus correspondence with researchers working in the field of aspirin and cancer.  This more wide-ranging approach reflected two considerations.  The first was the generally low number of reports coming forward on ad hoc randomised controlled trials on aspirin and cancer treatment.  The second was a recognition that often full publications in peer-reviewed journals were preceded by conference abstracts so the ongoing surveillance across all platforms was one valid method alongside contacting other research colleagues working in the field.   

In addition to this, a multi-disciplinary team called the Welsh Aspirin Group met frequently to collect and critique the evolving literature.  Several members of the group were attendees at cancer conferences and thus able to identify directly any relevant material as well as generating contacts for correspondence.  It has to be recognised that all the methods used still allows the possibility of oversight yet every effort was made to mitigate this via the ongoing application of every approach.

For the studies identified, a simple summary table was constructed.  This was based on evolving knowledge of studies where there were clearly substantial differences in the diagnostics groups of patients enrolled, the methodological approaches and measures of impact, the dose of aspirin and the other cancer treatments used.  A descriptive table was therefore considered the best way to present a heterogeneous set of results and allow a small number of interpretations to be made.  No attempt was made to undertake any meta-analysis given the anticipated low number of papers and the heterogeneity between the studies.  No attempts were also made to estimate impacts on single measures across the studies, such as impact on quantity or quality of life from aspirin.  By simply intending to produce a summary table, the studies are thus presented in a readily accessible format.  For each paper summarised, a basic and short summary of the key points are therefore presented. Results : Table 1 sets out a summary of the findings.  The findings are broadly divided into 2 groups, namely those in the last century and those reported since 2019.  The former covers 545 patients with three types of cancer (15-17) and on either placebo or high doses of aspirin exceeding 1,000 mg of aspirin per day.  The latter covers 7,779 patients with six types of cancer and on lower doses of aspirin that are within the range usually associated with the treatment of vascular disease (18-24).

Table 1 : Systematic review of randomised controlled trials of aspirin as an additional treatment of cancer

A literature search was undertaken to identify randomised controlled trials of aspirin in patients diagnosed with cancer. Excluded from the search were prevention trials that subsequently reported either cancer incidence or survival.

Study	Summary
66 patients with colorectal cancer (Lipton 1982)	Patients were randomised to aspirin 600 mg twice per day or placebo. No difference in disease free survival and overall survival and no evidence that metastases was reduced
176 patients with renal cell cancer (Cregan 1991)	Patients were randomised to aspirin 600 mg four times per day or placebo + interferon. Median survival of 8.8 month with aspirin v 8 month with placebo – not significant result
303 patients with lung cancer (Lebeau 1993)	Patients were randomised to receive 1,000 mg aspirin per day or placebo alongside chemotherapy. No difference in overall survival and no impact on extent of the disease
2,253 cancer patients (Joharatnam-Hogan 2019)	Gastro-oesophageal, colorectal cancer and prostate cancer patients.  Initial report only gives reassurance that 100 mg per day aspirin is well tolerated with cancer outcome data awaited
122 gynaecological cancer patients (Banerjee 2021)	Primarily ovarian cancer, the additional of aspirin at 320 mg per day did not improve the efficacy of combinations of chemotherapy. No data was reported on the cancer survival
95 gastric cancer patients (Jafa 2022)	Aspirin at 150 mg per day did not improve disease free survival or overall survival with standard chemotherapy. Response to chemotherapy with aspirin raised but not significant
3,021 patients with breast cancer (Chen 2024)	Patients were randomised to receive 300 mg daily per day or placebo to measure disease recurrence. Aspirin associated with non-significant increase of 25% of disease recurrence
112 colon cancer patients (Güller 2024)	Aspirin 100 mg per day showed a non-significant 43% improvement of disease free survival in a subgroup of patients with a genetic mutation, namely PIK3CA-mutant colon cancer
1,550 colorectal cancer patients (Chia 2025)	Aspirin 200mg per day gave a non-significant 9% survival alongside standard treatment. 20% did not have chemotherapy and those on aspirin had a suggestion of a survival advantage
626 colorectal cancer patients (Martling 2025)	Aspirin 160 mg per day in patients with PIK3 mutations reduced cancer recurrence by a 50% which was statistically significant.  First standalone trial to show statistical significance.

The overall picture was that aspirin was well tolerated alongside standard treatments and there were no reports of excessive risks of side effects classically associated with this medicine, such as bleeding.  One paper (21) was an outlier by reporting an excess – not statistically significant – in relapse of breast cancer.  Whilst most trials reported inconclusive results, the three most recent papers on colon and colorectal cancer were consistent with a trend toward benefit (22-24) with one showing a statistically significant benefit in a subgroup of colorectal cancer patients with a genetic mutation (24).    It therefore appears there is considerable heterogeneity of findings so cautious interpretation is needed. 

Another observation is that in all studies, aspirin was used alongside evidence-based treatments for cancer.  Whether or not aspirin adds value to such treatments is still unclear, which raises another possibility.  For some patients who either decline or are unable to afford cancer treatments, aspirin might be an option.  This could be particularly relevant in developing countries where provision of healthcare services for cancer is either scarce or unaffordable for some members of the population.  Thus, in such situations a low-cost and easily available medicine like aspirin could be highly relevant.

It can also be seen that there are many cancers omitted from trials.  This includes major causes of disease and death, such as pancreatic, brain, bladder, gall-bladder and cancer of unknown primary.  In the absence of trials for these cancers, the best available evidence comes from other sources such as observational studies (10) which highlight a broad benefit of aspirin in many forms of the disease.  

Finally, all of the studies were conducted in adults.  Of course, children and teenagers also experience cancer and it appears that this group of patients have been either ignored or omitted from being included in randomised controlled trials of aspirin.  Acknowledging the risks associated with aspirin, there have been previous calls for trials of aspirin to be considered in younger patients with cancer (25).  This current analysis therefore seems to offer a timely opportunity to re-state that call for action.

Discussion : Whilst a lot of questions remain to be answered, the overall body of evidence suggests a favourable benefit versus risk balance for cancer patients to consider taking aspirin.  Whilst it is premature for aspirin to be recommended as a routine treatment for all cancers- it is only currently used in a few selected blood cancers – it still seems timely for cancer patients to be informed of the current evidence and allowed to make informed choices.  As a further factor in this, it appears that some cancer treatments can adversely affect vascular disease risk (26) and given aspirin is also used in this situation, this is perhaps another reason to consider aspirin alongside standard treatment.

Aspirin is already used in some blood cancers, namely the myeloproliferative neoplasms.  The potential for other bone and blood cancers to be included in randomised controlled trials of aspirin also deserves consideration.  Of course, such consideration needs to take account of potential risks of aspirin and where patients have contraindications to the medicine, then they might be excluded.     

The very tight focus of randomised controlled trials of aspirin on the more common and survivable cancers, such as colorectal, excluded a large population of cancer patients with poor prognosis.  Whilst a general information campaign on aspirin and cancer seems valid, it could be argued that patients with aggressive disease such as pancreatic cancer are very good candidates to consider taking aspirin.  Pro-active discussions between clinicians and patients now seem highly justified in such situations.

The potential negative effect of stopping aspirin after a cancer diagnosis really needs further work and a pre-cautionary basis might be prudent.  The practice of de-prescribing aspirin in advanced cancer (27) may have detrimental effects so one valuable line of action could be to audit current use of aspirin when patients are diagnosed with cancer.  Such an audit would then also be valuable to monitor increased or decreases in aspirin use allowing observational studies on outcomes to be conducted.    

In developing countries, aspirin could be particularly valuable and there is an under-use of aspirin in developing countries now for use in vascular disease (28).  It might be timely for international health bodies, such as the World Health Organisation, to consider the situation as to how the health benefits of aspirin could be achieved globally.  Pharmaceutical companies might also be pro-actively involved in developing solutions for this in respect of their ability to provide aspirin to such a large population.

References 

1. Elwood PC, Cochrane AL, Burr ML, Sweetnam PM, Williams G, Welsby E, Hughes SJ, Renton R. A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. BMJ. 1974 Mar 9;1(5905):436-40. doi: 10.1136/bmj.1.5905.436. PMID: 4593555; PMCID: PMC1633246.
2. Collaborative overview of randomised trials of antiplatelet therapy–I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ. 1994 Jan 8;308(6921):81-106. Erratum in: BMJ 1994 Jun 11;308(6943):1540. PMID: 8298418; PMCID: PMC2539220.
3. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. doi: 10.1136/bmj.324.7329.71. Erratum in: BMJ 2002 Jan 19;324(7330):141. PMID: 11786451; PMCID: PMC64503.
4. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003 Jun 28;326(7404):1419. doi: 10.1136/bmj.326.7404.1419. Erratum in: BMJ. 2003 Sep 13;327(7415):586. Erratum in: BMJ. 2006 Sep;60(9):823. PMID: 12829553; PMCID: PMC162259.
5. Elwood PC, Morgan G, Brown G, Pickering J. Aspirin for everyone older than 50? For. BMJ. 2005 Jun 18;330(7505):1440-1. doi: 10.1136/bmj.330.7505.1440. PMID: 15961818; PMCID: PMC558385.
6. Baigent C. Aspirin for everyone older than 50? Against. BMJ. 2005 Jun 18;330(7505):1442-3. doi: 10.1136/bmj.330.7505.1442. PMID: 15961819; PMCID: PMC558386.
7. Milton S, McIntosh J, Yogaparan T, Alphonse P, Saya S, Karnchanachari N, Nguyen P, Lau P, Macrae F, Emery J. Clinicians’ opinions on recommending aspirin to prevent colorectal cancer to Australians aged 50-70 years: a qualitative study. BMJ Open. 2021 Feb 5;11(2):e042261. doi: 10.1136/bmjopen-2020-042261. PMID: 33550247; PMCID: PMC7925937.
8. Morgan GP, Williams JG. Therapeutic potential of aspirin in cancer of the colon. BMJ. 1993 Oct 16;307(6910):1007-8. doi: 10.1136/bmj.307.6910.1007-b. PMID: 8204142; PMCID: PMC1679189.
9. Elwood P, Protty M, Morgan G, Pickering J, Delon C, Watkins J. Aspirin and cancer: biological mechanisms and clinical outcomes. Open Biol. 2022 Sep;12(9):220124. doi: 10.1098/rsob.220124. Epub 2022 Sep 14. PMID: 36099932; PMCID: PMC9470249.
10. Elwood PC, Morgan G, Delon C, Protty M, Galante J, Pickering J, Watkins J, Weightman A, Morris D. Aspirin and cancer survival: a systematic review and meta-analyses of 118 observational studies of aspirin and 18 cancers. Ecancermedicalscience. 2021 Jul 2;15:1258. doi: 10.3332/ecancer.2021.1258. PMID: 34567243; PMCID: PMC8426031.
11. Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012 Apr 28;379(9826):1591-601. doi: 10.1016/S0140-6736(12)60209-8. Epub 2012 Mar 21. PMID: 22440947.
12. Elwood PC, Morgan G, Galante J, Chia JW, Dolwani S, Graziano JM, Kelson M, Lanas A, Longley M, Phillips CJ, Pickering J, Roberts SE, Soon SS, Steward W, Morris D, Weightman AL. Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk. PLoS One. 2016 Nov 15;11(11):e0166166. doi: 10.1371/journal.pone.0166166. PMID: 27846246; PMCID: PMC5113022.
13. Elwood P, Morgan G, Watkins J, Protty M, Mason M, Adams R, Dolwani S, Pickering J, Delon C, Longley M. Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against. Br J Cancer. 2024 Jan;130(1):3-8. doi: 10.1038/s41416-023-02506-5. Epub 2023 Nov 29. PMID: 38030748; PMCID: PMC10782022.
14. Morgan G, Watkins J, Protty M, Elwood P.  Health Economic Calculations on Low-Dose Aspirin and as an Additional Cancer Therapy.  Journal of Cancer Research 2025 https://www.wecmelive.com/open-access/health-economic-calculations-on-lowdose-aspirin-and-as-an-additional-cancer-therapy.pdf
15. Lipton A, Scialla S, Harvey H, Dixon R, Gordon R, Hamilton R, Ramsey H, Weltz M, Heckard R, White D. Adjuvant antiplatelet therapy with aspirin in colo-rectal cancer. J Med. 1982;13(5-6):419-29. PMID: 6963332.
16. Creagan ET, Twito DI, Johansson SL, Schaid DJ, Johnson PS, Flaum MA, Buroker TR, Geeraerts LH, Veeder MH, Gesme DH Jr, et al. A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma. J Clin Oncol. 1991 Dec;9(12):2104-9. doi: 10.1200/JCO.1991.9.12.2104. PMID: 1960551.
17. Lebeau B, Chastang C, Muir JF, Vincent J, Massin F, Fabre C. No effect of an antiaggregant treatment with aspirin in small cell lung cancer treated with CCAVP16 chemotherapy. Results from a randomized clinical trial of 303 patients. The “Petites Cellules” Group. Cancer. 1993 Mar 1;71(5):1741-5. doi: 10.1002/1097-0142(19930301)71:5<1741::aid-cncr2820710507>3.0.co;2-q. PMID: 8383578.
18. Joharatnam-Hogan N, Cafferty F, Hubner R, Swinson D, Sothi S, Gupta K, Falk S, Patel K, Warner N, Kunene V, Rowley S, Khabra K, Underwood T, Jankowski J, Bridgewater J, Crossley A, Henson V, Berkman L, Gilbert D, Kynaston H, Ring A, Cameron D, Din F, Graham J, Iveson T, Adams R, Thomas A, Wilson R, Pramesh CS, Langley R; Add-Aspirin Trial Management Group. Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial. Lancet Gastroenterol Hepatol. 2019 Nov;4(11):854-862. doi: 10.1016/S2468-1253(19)30289-4. Epub 2019 Aug 30. PMID: 31477558.
19. Banerjee S, P.B. Ottevanger , A. Sarivalasis , R. Le Scodan , A. Montes, J.R. Kroep, M. Romeo Marin , A. Casado Herraez, M. Auvray-Kuentz , A.M. Westermann, B. Lucas, D. Dangaj, F. Herrera, A. Wolfer , C. Coens, M.B. Vanlancker, L. Kandalaft, G. Coukos  Principal results of the EORTC-1508 trial: A phase II randomised, multicentre study of bevacizumab vs atezolizumab and bevacizumab with acetylsalicylic acid or placebo in recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal adenocarcinoma.  Annals of Oncology 2021.  https://www.annalsofoncology.org/article/S0923-7534(21)04413-6/pdf
20. Jafa E, L C, Nisha Y, Kate V, Kayal S, Ganesh RN, V C S, Ganesan P, Penumadu P, Dubashi B. Comparison of Efficacy of Aspirin Plus EOX vs. EOX Alone in Patients with Locally Advanced and Metastatic Gastric Cancer: a Randomized Clinical Trial. J Gastrointest Cancer. 2023 Jun;54(2):642-650. doi: 10.1007/s12029-022-00845-9. Epub 2022 Jul 16. PMID: 35842566.
21. Chen WY, Ballman KV, Partridge AH, Hahn OM, Briccetti FM, Irvin WJ, Symington B, Visvanathan K, Pohlmann PR, Openshaw TH, Weiss A, Winer EP, Carey LA, Holmes MD. Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial. JAMA. 2024 May 28;331(20):1714-1721. doi: 10.1001/jama.2024.4840. PMID: 38683596; PMCID: PMC11059055.

• U. Güller,  S. Hayoz, D.  Horber, S. DeDosso, D. Koeberle, S.Schacher Kaufmann, R.I. Inauen, M. Stahl, T. Delaunoit

, T.J. Ettrich, G.M. Bodoky, P. Michel, T. Kössler, K. Rothgiesser, S. Calmonte, M. Joerger512O Adjuvant aspirin treatment in PIK3CA mutated colon cancer patients: The phase III, prospective-randomized placebo-controlled multicenter SAKK 41/13 trial.  Annals of Oncology 2024.  https://www.annalsofoncology.org/article/S0923-7534(24)02100-8/fulltext 

• Chia JWK, Segelov E, Deng Y, Ho GF, Wang W, Han S, Sharma A, Ding K, Chen G, Jeffery MG, Tham CK, Ahn JB, Nott L, Zielinski R, Chao TY, van Hagen T, Wei PL, Day F, Mehta S, Yau T, Peng J, Hayes TM, Li Y, Gandhi M, Foo EMJ, Rahman N, Rothwell P, Ali R, Simes J, Toh HC. Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2025 Jan 14:S2468-1253(24)00387-X. doi: 10.1016/S2468-1253(24)00387-X. Epub ahead of print. PMID: 39824200.
• Martling A, Lindberg J, Myrberg IH, et al. Low-dose aspirin to reduce recurrence rate in colorectal cancer patients with PI3K pathway alterations: 3-year results from a randomized placebo-controlled trial. J Clin Oncol. 2025;43(4):LBA125.
• Morgan, G. Aspirin as adjuvant therapy in childhood cancer?. Br J Cancer 2021;106:240. https://doi.org/10.1038/bjc.2011.467
• Liu S, Horowitz JD, Koczwara B, Sverdlov AL, Packer N, Clark RA. Cardiac events among a cohort of 17,389 patients receiving cancer chemotherapy: short and long term implications. Cardiooncology. 2024 Oct 16;10(1):72. doi: 10.1186/s40959-024-00269-3. PMID: 39415228; PMCID: PMC11481733.
• Murphy L, Brown C, Smith A, Cranfield F, Sharp L, Visvanathan K, Bennett K, Barron TI. End-of-life prescribing of aspirin in patients with breast or colorectal cancer. BMJ Support Palliat Care. 2019 Mar;9(1):e6. doi: 10.1136/bmjspcare-2017-001370. Epub 2017 Aug 24. PMID: 28838931.
• Yoo SGK, Chung GS, Bahendeka SK, Sibai AM, Damasceno A, Farzadfar F, Rohloff P, Houehanou C, Norov B, Karki KB, Azangou-Khyavy M, Marcus ME, Aryal KK, Brant LCC, Theilmann M, Cífková R, Lunet N, Gurung MS, Mwangi JK, Martins J, Haghshenas R, Sturua L, Vollmer S, Bärnighausen T, Atun R, Sussman JB, Singh K, Saeedi Moghaddam S, Guwatudde D, Geldsetzer P, Manne-Goehler J, Huffman MD, Davies JI, Flood D. Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries. JAMA. 2023 Aug 22;330(8):715-724. doi: 10.1001/jama.2023.12905. PMID: 37606674; PMCID: PMC10445202.

For further information on the work of the Welsh Aspirin Group, see our website at:

www.welshaspiringroup.org

April 21^st 2025.