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Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study:a double-blind, randomised, placebo-controlled trial
- Source :
- Burn, J, Sheth, H, Elliott, F, Reed, L, Macrae, F, Mecklin, J P, Möslein, G, McRonald, F E, Bertario, L, Evans, D G, Gerdes, A M, Ho, J W C, Lindblom, A, Morrison, P J, Rashbass, J, Ramesar, R, Seppälä, T, Thomas, H J W, Pylvänäinen, K, Borthwick, G M, Mathers, J C, Bishop, D T, Boussioutas, A, Brewer, C, Cook, J, Eccles, D, Ellis, A, Hodgson, S V, Lubinski, J, Maher, E R, Porteous, M EM, Sampson, J, Scott, R J, Side, L & CAPP2 Investigators 2020, ' Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study : a double-blind, randomised, placebo-controlled trial ', The Lancet, vol. 395, no. 10240, pp. 1855-1863 . https://doi.org/10.1016/S0140-6736(20)30366-4, Evans, D G & et al. 2020, ' Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study : a double-blind, randomised, placebo-controlled trial ', Lancet, vol. 395, no. 10240, pp. 1855-1863 . https://doi.org/10.1016/S0140-6736(20)30366-4
- Publication Year :
- 2020
-
Abstract
- BACKGROUND: Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population.METHODS: In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [FINDINGS: Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43-0·97; p=0·035) for aspirin versus placebo. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39-0·87; p=0·0085). Per-protocol analyses restricted to 509 who achieved 2 years' intervention gave an HR of 0·56 (0·34-0·91; p=0·019) and an incidence rate ratio of 0·50 (0·31-0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43-0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously.INTERPRETATION: The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results.FUNDING: Cancer Research UK, European Union, MRC, NIHR, Bayer Pharma AG, Barbour Foundation.
- Subjects :
- RESISTANT STARCH
Placebo-controlled study
030204 cardiovascular system & hematology
0302 clinical medicine
Life Tables
030212 general & internal medicine
11 Medical and Health Sciences
media_common
RISK
Aspirin
education.field_of_study
Anti-Inflammatory Agents, Non-Steroidal
LOW-DOSE ASPIRIN
General Medicine
Lynch syndrome
3. Good health
Intention to Treat Analysis
Anti-Inflammatory Agents, Non-Steroidal/adverse effects
medicine.drug
CHEMOPREVENTION
medicine.medical_specialty
Heterozygote
3122 Cancers
Population
NEOPLASIA
Aspirin/adverse effects
Placebo
CAPP2 Investigators
Medication Adherence
03 medical and health sciences
Double-Blind Method
Internal medicine
General & Internal Medicine
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
BENEFITS
medicine
media_common.cataloged_instance
Humans
European union
education
Proportional Hazards Models
Intention-to-treat analysis
Cancer prevention
business.industry
MORTALITY
3126 Surgery, anesthesiology, intensive care, radiology
medicine.disease
Colorectal Neoplasms, Hereditary Nonpolyposis
business
Follow-Up Studies
Subjects
Details
- Language :
- English
- ISSN :
- 01406736
- Database :
- OpenAIRE
- Journal :
- Burn, J, Sheth, H, Elliott, F, Reed, L, Macrae, F, Mecklin, J P, Möslein, G, McRonald, F E, Bertario, L, Evans, D G, Gerdes, A M, Ho, J W C, Lindblom, A, Morrison, P J, Rashbass, J, Ramesar, R, Seppälä, T, Thomas, H J W, Pylvänäinen, K, Borthwick, G M, Mathers, J C, Bishop, D T, Boussioutas, A, Brewer, C, Cook, J, Eccles, D, Ellis, A, Hodgson, S V, Lubinski, J, Maher, E R, Porteous, M EM, Sampson, J, Scott, R J, Side, L & CAPP2 Investigators 2020, ' Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study : a double-blind, randomised, placebo-controlled trial ', The Lancet, vol. 395, no. 10240, pp. 1855-1863 . https://doi.org/10.1016/S0140-6736(20)30366-4, Evans, D G & et al. 2020, ' Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study : a double-blind, randomised, placebo-controlled trial ', Lancet, vol. 395, no. 10240, pp. 1855-1863 . https://doi.org/10.1016/S0140-6736(20)30366-4
- Accession number :
- edsair.doi.dedup.....b883398de7c0cc7e549ca68d176f77a1