TY - JOUR
T1 - Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer
T2 - 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, 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
PY - 2011/12/17
Y1 - 2011/12/17
N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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.INTERPRETATION: 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.FUNDING: 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 - BACKGROUND: 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.METHODS: 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.RESULTS: 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.INTERPRETATION: 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.FUNDING: 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/prevention & control
KW - Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
KW - Aspirin/therapeutic use
KW - Chemoprevention
KW - Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
KW - Dietary Carbohydrates/therapeutic use
KW - Double-Blind Method
KW - Heterozygote
KW - Humans
KW - Starch/therapeutic use
UR - https://www.sciencedirect.com/science/article/pii/S0140673611610490
U2 - 10.1016/S0140-6736(11)61049-0
DO - 10.1016/S0140-6736(11)61049-0
M3 - Article
C2 - 22036019
SN - 0140-6736
VL - 378
SP - 2081
EP - 2087
JO - The Lancet
JF - The Lancet
IS - 9809
ER -