Drugs To Prevent Colon Cancer Show Promise, But Hurdles Remain for Chemoprevention

Abstract

A low-dose combination of sulindac and difluoromethylornithine (DFMO) reduced the risk of recurrent colorectal adenomas by 70% and high-risk adenomas by 92% compared with placebo in a randomized controlled trial, researchers reported in April at the annual meeting of the American Association for Cancer Research (AACR). Also, 5-year follow-up data from the Adenoma Prevention with Celecoxib (APC) trial showed that individuals who took celecoxib during the trial continued to be at lower risk of developing adenomas 2 years after they stopped taking the drug, compared with participants who took a placebo. These results could fundamentally change chemoprevention, experts agree. The magnitude of the benefi t in the sulindac – DFMO trial was larger than expected for any type of chemoprevention. (As designed, the trial would have been deemed a success if the combination had reduced the risk by 50%.) And the trial is the fi rst to show that a combination of chemoprevention drugs is effective and safe. The APC data show that the use of nonsteroidal antiinfl ammatory drugs, specifi cally a cyclooxygenase-2 (COX-2) inhibitor, reduces the development of adenomas instead of just masking the presence of lesions. “The fi eld of [nonsteroidal antiinfl ammatory drugs] and COX-2 inhibitors — and in some people’s minds, the entire concept of chemoprevention — was in ashes when the COX-2 selective inhibitor [toxicity] reports came out in 2005,” said Scott Lippman, M.D. , professor and chair of thoracic and head and neck medical oncology at the University of Texas M. D. Anderson Cancer Center in Houston. Those reports, showing that celecoxib and rofecoxib (Vioxx) increased the risk of cardiovascular disease and death, garnered so much attention that when researchers reported the initial effi cacy data from the APC trial in 2006, few noticed. “I think what we are seeing now in these two very important trials is that the phoenix is rising,” Lippman said.