Chemoprevention after polipectomy. Giuseppe Aprile Gianpiero Fasola Dipartimento di Oncologia Azienda Ospedaliero-Universitaria di Udine. Why is chemoprevention so complicated? Different studies with different endpoints, in different populations.
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Chemoprevention after polipectomy
Dipartimento di Oncologia
Azienda Ospedaliero-Universitaria di Udine
Why is chemoprevention so complicated?
Different studies with different endpoints, in different populations
Drug companies contributed to the land of confusion
Systematic review of the available evidence (1970-2005) on the effectiveness of aspirin for the chemoprevention of colic adenomas, CRC, and CRC mortality, as well as potential harms.
Metanalisi di RCT sul ruolo dell’aspirina nella chemioprevenzione dell’adenoma colorettale
Cole BF, et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. JNCI 2009
Is Adenoma Recurrence a Useful Surrogate for CRC Risk?
Most small adenomatous polyps do not progress to malignancy
Probability that a small adenoma contains high grade dysplasia/malignant changes is small (2%)
Average transition time from small adenoma to invasive cancer > 10 years
National Polyp Study. N Engl J Med,1993
10,000/15 = 700 treated for one cancer prevented
700 healthy people at risk for each person who benefits
1 treated for one therapeutic effect
1 person at risk for each person who benefits
Safety: Study Population
Geriatric patient (>70 yrs, >85 yrs if surgeon) susceptibilities
Severe drug toxicity
Potential for drug toxicity related to chronic administration
Reduction of adenoma growth but dysplasia and CRCchanges may continue
Celecoxib: 2001 FDA approved for adenomatous polyp prevention for individuals with FAP
These data and retrospective data have led to extensive study of COX-2 inhibitors for sporadic adenomas as well
Follow-up = 3,327 pt-years
CV Adverse events (%)
Placebo (2%) RR=1.0
25 mg QD (3.6%) RR=1.9
Follow-up = 2.8-3.1 years
CV deaths (%)
Placebo (1%); RR=1.0
200 mg BID (2.3%) RR=2.3
400 mg BID (3.4%) RR=3.4
N Engl J Med. 2005;352:1071-80
N Engl J Med. 2005;352:1092-102
Psaty and Potter, N Engl J Med 2006
Reviewed APC and PreSAP trials and concluded:
Kerr D et al. N Engl J Med 2007
Rofecoxib and cardiovascular adverse events in adjuvant treatment of CRC
Reviewed VICTORe trial CV events, after a median treatment duration of 7.5 months:
Do you see any improvement?