Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial
Hubner, Richard A
AffiliationMRC Clinical Trials Unit, University College London, UKMRC Clinical Trials Unit, University College London, UK
MetadataShow full item record
AbstractBACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer. METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment. FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0á5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants). INTERPRETATION: Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes. FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.
CitationJoharatnam-Hogan N, Cafferty F, Hubner R, Swinson D, Sothi S, Gupta K, et al. Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial. Lancet Gastroenterology & Hepatology. 2019 Aug 30.
JournalLancet Gastroenterology & Hepatology
- 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.
- Authors: Coyle C, Cafferty FH, Rowley S, MacKenzie M, Berkman L, Gupta S, Pramesh CS, Gilbert D, Kynaston H, Cameron D, Wilson RH, Ring A, Langley RE, Add-Aspirin investigators.
- Issue date: 2016 Nov
- Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial.
- Authors: Herbst RS, Arkenau HT, Santana-Davila R, Calvo E, Paz-Ares L, Cassier PA, Bendell J, Penel N, Krebs MG, Martin-Liberal J, Isambert N, Soriano A, Wermke M, Cultrera J, Gao L, Widau RC, Mi G, Jin J, Ferry D, Fuchs CS, Petrylak DP, Chau I
- Issue date: 2019 Aug
- 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.
- Authors: Hull MA, Sprange K, Hepburn T, Tan W, Shafayat A, Rees CJ, Clifford G, Logan RF, Loadman PM, Williams EA, Whitham D, Montgomery AA, seAFOod Collaborative Group.
- Issue date: 2018 Dec 15
- AVURT: aspirin versus placebo for the treatment of venous leg ulcers - a Phase II pilot randomised controlled trial.
- Authors: Tilbrook H, Clark L, Cook L, Bland M, Buckley H, Chetter I, Dumville J, Fenner C, Forsythe R, Gabe R, Harding K, Layton A, Lindsay E, McDaid C, Moffatt C, Rolfe D, Sbizzera I, Stansby G, Torgerson D, Vowden P, Williams L, Hinchliffe R
- Issue date: 2018 Oct
- Metformin in non-diabetic hyperglycaemia: the GLINT feasibility RCT.
- Authors: Griffin SJ, Bethel MA, Holman RR, Khunti K, Wareham N, Brierley G, Davies M, Dymond A, Eichenberger R, Evans P, Gray A, Greaves C, Harrington K, Hitman G, Irving G, Lessels S, Millward A, Petrie JR, Rutter M, Sampson M, Sattar N, Sharp S
- Issue date: 2018 Apr