Statins had no chemoprotective effect on colorectal cancer risk

AACR 101st Annual Meeting

Statins did not protect against colorectal adenomas, and in patients at high risk for developing these lesions, they may have increased the risk for developing benign colorectal tumors, according to results of a secondary analysis of the Adenoma Prevention with Celecoxib trial.

“Given our results, we do not think that it is reasonable to further study statins for chemoprevention of colorectal cancer, as the chance that they have this activity is very small,” said Monica Bertagnolli, MD, chief of the division of surgical oncology at Brigham and Women’s Hospital and professor of surgery at Harvard Medical School.

Early data from this study showed a preventive effect of celecoxib in patients at increased risk for colorectal cancer.

For the randomized trial, researchers examined whether statin use was associated with recurrent colorectal adenomas after colonoscopy in 2,035 patients with colorectal adenomas. Patients were randomly assigned to one of three treatment arms: placebo (n=679), 200 mg celecoxib (Celebrex, Pfizer) twice-daily (n=685) or 400 mg celecoxib twice-daily (n=671).

Researchers collected complete medical history, medication use and performed colonoscopic surveillance until five years after enrollment. Multivariable Cox regression assessed the effects of statin use on newly detected adenomas and cardiovascular adverse events.

The findings were presented by Bertagnolli at the American Association for Cancer Research 101st Annual Meeting.

Thirty-six percent of patients used statins. After adjusting for covariates, including aspirin use, age and sex, participants assigned placebo who used statins at any time had no benefit during five years when compared with never users (RR=1.24; P=.065).

The risk for adenoma during a five-year period increased in those who used a statin for more than three years (RR=1.39; P=.024).

For all comparisons of patients treated with celecoxib, adenoma detection rates for statin users and non-users were equivalent. Patients assigned to statins experienced more serious cardiovascular side effects, such as myocardial infarction and stroke.

“We were surprised by our findings; pre-clinical studies indicated that statins would be beneficial, but they were not,” Bertagnolli said. “The observation that adenomas were more frequent in patients using statins needs to be confirmed and, because of this secondary analysiss study design, should not raise concern. It would be highly detrimental if people at risk for cardiovascular disease were to stop taking statins based on these data.”

In an accompanying editorial, John A. Baron, MD, of the departments of medicine and of community and family medicine at Dartmouth Medical School in Hanover, N.H., wrote, “The negative data that Bertagnolli et al provide add to the accumulating evidence that, at least overall, statins probably do not prevent colorectal neoplasia, although it is conceivable that there are benefits with high cumulative doses or in genetically defined subgroups. It may not be the end of the road for statins and the colorectum, but certainly, the route to the hoped-for destination is getting more difficult.” – by Jennifer Southall

I found the results quite disappointing. It shows pre-clinical studies don't always predict actual benefit when using a drug, and that the biology of colorectal adenoma and cancer formation is complex. Certainly our knowledge in this arena is sub par. We still hold out hope for the preventive effect of NSAIDs. Indeed Dr. Bertagnolli's group (the CALGB), in conjunction with SWOG, will be running a trial in which patients at high risk for recurrence of colon cancer after complete resection are randomized to chemotherapy plus or minus celecoxib.

– Charles D. Blanke, MD, FACP
HemOnc Today Editorial Board member

For more information:

• Bertagnolli M. #LB-173. Presented at: AACR 101st Annual Meeting; April 17-21, 2010; Washington, D.C.

More Meeting Highlights>>

Follow HemOncToday.com on Twitter.