Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial

TY - JOUR

T1 - Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial

AU - Burn, John

AU - Gerdes, Anne-Marie

AU - Macrae, Finlay

AU - Mecklin, Jukka-Pekka

AU - Moeslein, Gabriela

AU - Olschwang, Sylviane

AU - Eccles, Diane

AU - Evans, D Gareth

AU - Maher, Eamonn R

AU - Bertario, Lucio

AU - Bisgaard, Søs Marie Luise

AU - Dunlop, Malcolm G

AU - Ho, Judy W C

AU - Hodgson, Shirley V

AU - Lindblom, Annika

AU - Lubinski, Jan

AU - Morrison, Patrick J

AU - Murday, Victoria

AU - Ramesar, Raj

AU - Side, Lucy

AU - Scott, Rodney J

AU - Thomas, Huw J W

AU - Vasen, Hans F

AU - Barker, Gail

AU - Crawford, Gillian

AU - Elliott, Faye

AU - Movahedi, Mohammad

AU - Pylvanainen, Kirsi

AU - Wijnen, Juul T

AU - Fodde, Riccardo

AU - Lynch, Henry T

AU - Mathers, John C

AU - Bishop, D Timothy

AU - CAPP2 Investigators

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2011

Y1 - 2011

N2 - Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95 CI 0·35-1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95 CI 0·32- 0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19-0·86, p=0·02) and an IRR of 0·37 (0·18-0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. European Union; Cancer Research UK; Bayer Corporation; National Starch and Chemical Co; UK Medical Research Council; Newcastle Hospitals trustees; Cancer Council of Victoria Australia; THRIPP South Africa; The Finnish Cancer Foundation; SIAK Switzerland; Bayer Pharma.

AB - Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95 CI 0·35-1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95 CI 0·32- 0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19-0·86, p=0·02) and an IRR of 0·37 (0·18-0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. European Union; Cancer Research UK; Bayer Corporation; National Starch and Chemical Co; UK Medical Research Council; Newcastle Hospitals trustees; Cancer Council of Victoria Australia; THRIPP South Africa; The Finnish Cancer Foundation; SIAK Switzerland; Bayer Pharma.

KW - Adenoma

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Aspirin

KW - Chemoprevention

KW - Colorectal Neoplasms, Hereditary Nonpolyposis

KW - Dietary Carbohydrates

KW - Double-Blind Method

KW - Heterozygote

KW - Humans

KW - Starch

U2 - 10.1016/S0140-6736(11)61049-0

DO - 10.1016/S0140-6736(11)61049-0

M3 - Journal article

C2 - 22036019

SN - 0140-6736

VL - 378

SP - 2081

EP - 2087

JO - Lancet

JF - Lancet

IS - 9809

ER -