ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours

Coyle, C.; Cafferty, Fay; Rowley, Samuel; MacKenzie, Mairead; Berkman, Lindy; Gupta, Sudeep; Pramesh, C.S.; Gilbert, Duncan C.; Kynaston, Howard; Cameron, David; Wilson, Richard H.; Ring, Alistair; Langley, Ruth E.

doi:10.1016/j.cct.2016.10.004

Cited by 134 publications

(107 citation statements)

References 43 publications

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“…Our observations are consistent with data showing that AA men have a distinct immune-inflammation signature in their tumors (10, 33–36) and support the hypothesis that aspirin targets inflammation as a driver of disease progression in AA men, thereby reducing lethal prostate cancer in this high-risk group of patients. Recently, a large randomized trial assessing the effects of aspirin on disease recurrence for prostate cancer and other solid cancers has been initiated in the United Kingdom (53). Our findings suggest that men of African descent should be part of the 2120 men recruited into the prostate cancer arm of the trial.…”

Section: Discussionmentioning

confidence: 99%

Aspirin Use Reduces the Risk of Aggressive Prostate Cancer and Disease Recurrence in African-American Men

Smith

Dorsey

Tang

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Men of African descent experience a disproportionately high prostate cancer mortality. Intratumoral inflammation was found to be associated with aggressive prostate cancer. We and others have shown that prostate tumors in African-American (AA) patients harbor a distinct immune and inflammation signature when compared with European-American (EA) patients. These observations suggest that inflammation could be a driver of aggressive disease in men of African descent, leading to the hypothesis that an anti-inflammatory drug like aspirin could prevent disease progression. Methods We examined the relationship between aspirin use and prostate cancer in the NCI-Maryland Prostate Cancer Case-Control Study consisting of 823 men with incident prostate cancer (422 AA and 401 EA) and 1034 population-based men without the disease diagnosis (486 AA and 548 EA). Results We observed a significant inverse association between regular aspirin use and prostate cancer among AA men. Stratification of AA patients by disease stage showed that daily and long-term (> 3 years) aspirin use significantly decreased the risk of advanced disease (adjusted odds ratios for T3/T4 disease: 0.35, 95% CI: 0.17 to 0.73 and 0.22, 95% CI: 0.08 to 0.60, respectively), but not early-stage disease (T1/T2). Regular aspirin use also reduced disease recurrence in AA men. Conclusions Regular aspirin use is associated with a decreased risk of advanced stage prostate cancer and increased disease-free survival in AA men. Impact Regular aspirin use before and after a prostate cancer diagnosis may prevent the development of aggressive disease in AA men who are at risk of a lethal malignancy.

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Section: Discussionmentioning

confidence: 99%

Aspirin Use Reduces the Risk of Aggressive Prostate Cancer and Disease Recurrence in African-American Men

Smith

Dorsey

Tang

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Add-Aspirin, a phase III RCT of adjuvant aspirin therapy in four disease cohorts (gastro-oesophageal, breast, prostate and colorectal cancer) is currently recruiting 42 . Patients with adenocarcinoma, adenosquamous carcinoma or squamous cell carcinoma of the oesophagus, gastro-oesophageal junction or stomach are eligible for inclusion in the gastro-oesophageal cohort, and hence the inclusion criteria are broader than for STAT-ROC.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT-ROC feasibility study

Alexandre

Clark

Walton³

et al. 2020

BJS Open

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Background: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT.Methods: For this multicentre, double-blind, parallel-group, randomized, placebo-controlled feasibility trial, adults with OAC (including Siewert I-II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival.Results: A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26⋅7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low-density lipoprotein cholesterol levels by 3 months (adjusted mean difference −0⋅83 (95 per cent c.i. −1⋅4 to −0⋅22) mmol/l; P = 0⋅009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow-up. Adverse events were similar between the groups. Quality-of-life data were complete for 98⋅3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non-randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise.Conclusion: This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com).

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“…It may imply that the long‐term use of aspirin for younger generation shows stronger chemopreventive benefits . Another ongoing study using a double‐blind placebo RCT to investigate the effects of chemopreventive effects of aspirin in solid cancers, including CRC, is undertaken by a multicenter study in the UK . Further randomized evidence is warranted for a final verdict of the effect of aspirin in cancer recurrence.…”

Section: Discussionmentioning

confidence: 99%

Low‐dose aspirin can reduce colorectal cancer mortality after surgery: A 10‐year follow‐up of 13 528 colorectal cancer patients

Sung

Chan

et al. 2019

J of Gastro and Hepatol

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Background and Aim The chemopreventive effect of aspirin in colorectal cancer (CRC) is well studied, but its benefit in patients after CRC diagnosis and surgery is unclear. This study aims to investigate the effects of low‐dose aspirin use in mortality among CRC patients after surgery. Methods Patients were analyzed in two cohorts: (i) patients taking aspirin before CRC diagnosis and continued or discontinued aspirin after surgery and (ii) patients, who never used aspirin before CRC diagnosis, received or did not receive aspirin after surgery. CRC‐related mortality and all‐cause mortality were the primary and secondary outcomes. Sub‐distribution hazard ratio (SHR) for competing‐risk CRC mortality was fitted to adjust for other causes of death; hazard ratio (HR) was used to compare all‐cause mortality. Results A total of 13 528 CRC patients were included. Among 3292 patients with regular aspirin use before CRC diagnosis, 2658 (80.7%) continued aspirin and 634 (19.3%) discontinued aspirin after surgery. Continuous use of aspirin significantly reduced CRC‐related mortality (SHR: 0.69, 95% confidence interval [CI]: 0.59–0.81) and all‐cause mortality (HR: 0.61, 95% CI: 0.55–0.68). Among 10 236 patients who did not use aspirin before CRC diagnosis, 1054 patients (10.3%) received aspirin after surgery and 9182 (89.7%) did not. Aspirin initiated after surgery reduced CRC‐related mortality (SHR: 0.88, 95% CI: 0.80–0.98) and all‐cause mortality (HR: 0.87, 95% CI: 0.81–0.94). Conclusions Irrespective of aspirin use before surgery for CRC, low‐dose aspirin after surgery lowers risk of both CRC‐related mortality and overall mortality.

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ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours

Cited by 134 publications

References 43 publications

Aspirin Use Reduces the Risk of Aggressive Prostate Cancer and Disease Recurrence in African-American Men

Aspirin Use Reduces the Risk of Aggressive Prostate Cancer and Disease Recurrence in African-American Men

Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT-ROC feasibility study

Low‐dose aspirin can reduce colorectal cancer mortality after surgery: A 10‐year follow‐up of 13 528 colorectal cancer patients

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