Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial

Add-Aspirin Trial Management Group, Nalinie Joharatnam-Hogan, Fay Cafferty, Richard Hubner, Daniel Swinson, Sharmila Sothi, Kamalnayan Gupta, Stephen Falk, Kinnari Patel, Nicola Warner, Victoria Kunene, Sam Rowley, Komel Khabra, Tim Underwood, Janusz Jankowski, John Bridgewater, Anne Crossley, Verity Henson, Lindy Berkman, Duncan GilbertHoward Kynaston, Alistair Ring, David Cameron, Farhat Din, Janet Graham, Timothy Iveson, Richard Adams, Anne Thomas, Richard Wilson, C. S. Pramesh, Ruth Langley, John Burn, Sue Campbell, Lisa Capaldi, Yvonne Carse, Durga Gadgil, Arnold Goldman, Sudeep Gupta, Gregory Leonard, Mairead MacKenzie, Mahesh Parmar, Carlo Patrono, Russell Petty, Peter M. Rothwell, Robert J.C. Steele

Research output: Contribution to journalArticle

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Abstract

BackgroundPreclinical, 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.MethodsThe 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.FindingsAfter 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 (0·5%) 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).InterpretationAspirin 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.
Original languageEnglish
Pages (from-to)854-862
Number of pages9
JournalThe Lancet Gastroenterology and Hepatology
Volume4
Issue number11
DOIs
Publication statusPublished - 30 Aug 2019

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Aspirin
Esophageal Neoplasms
Neoplasms
Random Allocation
Therapeutics
Colorectal Neoplasms
Prostatic Neoplasms
Randomized Controlled Trials
Placebos
Breast Neoplasms
Hemorrhage
Dyspepsia
Tablets
Registries
Neoplasm Metastasis
Costs and Cost Analysis
Recurrence
Survival
Mortality

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Add-Aspirin Trial Management Group ; Joharatnam-Hogan, Nalinie ; Cafferty, Fay ; Hubner, Richard ; Swinson, Daniel ; Sothi, Sharmila ; Gupta, Kamalnayan ; Falk, Stephen ; Patel, Kinnari ; Warner, Nicola ; Kunene, Victoria ; Rowley, Sam ; Khabra, Komel ; Underwood, Tim ; Jankowski, Janusz ; Bridgewater, John ; Crossley, Anne ; Henson, Verity ; Berkman, Lindy ; Gilbert, Duncan ; Kynaston, Howard ; Ring, Alistair ; Cameron, David ; Din, Farhat ; Graham, Janet ; Iveson, Timothy ; Adams, Richard ; Thomas, Anne ; Wilson, Richard ; Pramesh, C. S. ; Langley, Ruth ; Burn, John ; Campbell, Sue ; Capaldi, Lisa ; Carse, Yvonne ; Gadgil, Durga ; Goldman, Arnold ; Gupta, Sudeep ; Leonard, Gregory ; MacKenzie, Mairead ; Parmar, Mahesh ; Patrono, Carlo ; Petty, Russell ; Rothwell, Peter M. ; Steele, Robert J.C. / Aspirin as an adjuvant treatment for cancer : feasibility results from the Add-Aspirin randomised trial. In: The Lancet Gastroenterology and Hepatology. 2019 ; Vol. 4, No. 11. pp. 854-862.
@article{d24e2b5550f341a484307afa632fea29,
title = "Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial",
abstract = "BackgroundPreclinical, 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.MethodsThe 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.FindingsAfter 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 (0·5{\%}) 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).InterpretationAspirin 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.",
author = "{Add-Aspirin Trial Management Group} and Nalinie Joharatnam-Hogan and Fay Cafferty and Richard Hubner and Daniel Swinson and Sharmila Sothi and Kamalnayan Gupta and Stephen Falk and Kinnari Patel and Nicola Warner and Victoria Kunene and Sam Rowley and Komel Khabra and Tim Underwood and Janusz Jankowski and John Bridgewater and Anne Crossley and Verity Henson and Lindy Berkman and Duncan Gilbert and Howard Kynaston and Alistair Ring and David Cameron and Farhat Din and Janet Graham and Timothy Iveson and Richard Adams and Anne Thomas and Richard Wilson and Pramesh, {C. S.} and Ruth Langley and John Burn and Sue Campbell and Lisa Capaldi and Yvonne Carse and Durga Gadgil and Arnold Goldman and Sudeep Gupta and Gregory Leonard and Mairead MacKenzie and Mahesh Parmar and Carlo Patrono and Russell Petty and Rothwell, {Peter M.} and Steele, {Robert J.C.}",
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language = "English",
volume = "4",
pages = "854--862",
journal = "Lancet Gastroenterology and Hepatology",
issn = "2468-1253",
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Add-Aspirin Trial Management Group, 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, Burn, J, Campbell, S, Capaldi, L, Carse, Y, Gadgil, D, Goldman, A, Gupta, S, Leonard, G, MacKenzie, M, Parmar, M, Patrono, C, Petty, R, Rothwell, PM & Steele, RJC 2019, 'Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial', The Lancet Gastroenterology and Hepatology, vol. 4, no. 11, pp. 854-862. https://doi.org/10.1016/S2468-1253(19)30289-4

Aspirin as an adjuvant treatment for cancer : feasibility results from the Add-Aspirin randomised trial. / Add-Aspirin Trial Management Group; Joharatnam-Hogan, Nalinie; Cafferty, Fay; Hubner, Richard; Swinson, Daniel; Sothi, Sharmila; Gupta, Kamalnayan; Falk, Stephen; Patel, Kinnari; Warner, Nicola; Kunene, Victoria; Rowley, Sam; Khabra, Komel; Underwood, Tim; Jankowski, Janusz; Bridgewater, John; Crossley, Anne; Henson, Verity; Berkman, Lindy; Gilbert, Duncan; Kynaston, Howard; Ring, Alistair; Cameron, David; Din, Farhat; Graham, Janet; Iveson, Timothy; Adams, Richard; Thomas, Anne; Wilson, Richard; Pramesh, C. S.; Langley, Ruth (Lead / Corresponding author); Burn, John; Campbell, Sue; Capaldi, Lisa; Carse, Yvonne; Gadgil, Durga; Goldman, Arnold; Gupta, Sudeep; Leonard, Gregory; MacKenzie, Mairead; Parmar, Mahesh; Patrono, Carlo; Petty, Russell; Rothwell, Peter M.; Steele, Robert J.C.

In: The Lancet Gastroenterology and Hepatology, Vol. 4, No. 11, 30.08.2019, p. 854-862.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aspirin as an adjuvant treatment for cancer

T2 - feasibility results from the Add-Aspirin randomised trial

AU - Add-Aspirin Trial Management Group

AU - Joharatnam-Hogan, Nalinie

AU - Cafferty, Fay

AU - Hubner, Richard

AU - Swinson, Daniel

AU - Sothi, Sharmila

AU - Gupta, Kamalnayan

AU - Falk, Stephen

AU - Patel, Kinnari

AU - Warner, Nicola

AU - Kunene, Victoria

AU - Rowley, Sam

AU - Khabra, Komel

AU - Underwood, Tim

AU - Jankowski, Janusz

AU - Bridgewater, John

AU - Crossley, Anne

AU - Henson, Verity

AU - Berkman, Lindy

AU - Gilbert, Duncan

AU - Kynaston, Howard

AU - Ring, Alistair

AU - Cameron, David

AU - Din, Farhat

AU - Graham, Janet

AU - Iveson, Timothy

AU - Adams, Richard

AU - Thomas, Anne

AU - Wilson, Richard

AU - Pramesh, C. S.

AU - Langley, Ruth

AU - Burn, John

AU - Campbell, Sue

AU - Capaldi, Lisa

AU - Carse, Yvonne

AU - Gadgil, Durga

AU - Goldman, Arnold

AU - Gupta, Sudeep

AU - Leonard, Gregory

AU - MacKenzie, Mairead

AU - Parmar, Mahesh

AU - Patrono, Carlo

AU - Petty, Russell

AU - Rothwell, Peter M.

AU - Steele, Robert J.C.

PY - 2019/8/30

Y1 - 2019/8/30

N2 - BackgroundPreclinical, 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.MethodsThe 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.FindingsAfter 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 (0·5%) 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).InterpretationAspirin 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.

AB - BackgroundPreclinical, 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.MethodsThe 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.FindingsAfter 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 (0·5%) 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).InterpretationAspirin 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.

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U2 - 10.1016/S2468-1253(19)30289-4

DO - 10.1016/S2468-1253(19)30289-4

M3 - Article

C2 - 31477558

AN - SCOPUS:85072866420

VL - 4

SP - 854

EP - 862

JO - Lancet Gastroenterology and Hepatology

JF - Lancet Gastroenterology and Hepatology

SN - 2468-1253

IS - 11

ER -

Add-Aspirin Trial Management Group, Joharatnam-Hogan N, Cafferty F, Hubner R, Swinson D, Sothi S et al. Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial. The Lancet Gastroenterology and Hepatology. 2019 Aug 30;4(11):854-862. https://doi.org/10.1016/S2468-1253(19)30289-4