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


CONCLUSIONS
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.


BACKGROUND
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.
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. john.burn@ncl.ac.uk
John
J
Burn
Anne-Marie
AM
Gerdes
Finlay
F
Macrae
Jukka-Pekka
JP
Mecklin
Gabriela
G
Moeslein
Sylviane
S
Olschwang
Diane
D
Eccles
D Gareth
DG
Evans
Eamonn R
ER
Maher
Lucio
L
Bertario
Marie-Luise
ML
Bisgaard
Malcolm G
MG
Dunlop
Judy W C
JW
Ho
Shirley V
SV
Hodgson
Annika
A
Lindblom
Jan
J
Lubinski
Patrick J
PJ
Morrison
Victoria
V
Murday
Raj
R
Ramesar
Lucy
L
Side
Rodney J
RJ
Scott
Huw J W
HJ
Thomas
Hans F
HF
Vasen
Gail
G
Barker
Gillian
G
Crawford
Faye
F
Elliott
Mohammad
M
Movahedi
Kirsi
K
Pylvanainen
Juul T
JT
Wijnen
Riccardo
R
Fodde
Henry T
HT
Lynch
John C
JC
Mathers
D Timothy
DT
Bishop
D000236:Adenoma / Q000517:prevention & control; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D018890:Chemoprevention; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000517:prevention & control*; D004040:Dietary Carbohydrates / Q000627:therapeutic use; D004311:Double-Blind Method; D006579:Heterozygote; D006801:Humans; D013213:Starch / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004040:Dietary Carbohydrates; D013213:Starch; D001241:Aspirin