A COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer

Abstract

Dear Editor: We would like to comment on the paper by Jacobsen et al., which examined the possible effects of adding a COX-2 inhibitor to an established preoperative chemoradiotherapy regimen in locally advanced colorectal cancer. It is very unfortunate that the severe dermatological reaction reported by the authors occurred as this clearly limited the interpretability and usefulness of this study. Selective COX-2 inhibitors have also been criticised for severe cardiovascular side effects, but clearly these were not seen in this study, probably due to compliance issues and short treatment duration. The principle behind this investigation does merit further study. The role of aberrant COX-2 expression in epithelial cancers, for example, breast and colorectal cancer, is undisputed. More controversial is the proposition that measures to inhibit COX-2 expression might be beneficial in preventing malignancy or treating actual cancer patients. Results of epidemiological observation studies of NSAID or COX-2 inhibitor use generally support a preventitive role, but prospective randomised studies using these agents have not supported these findings. This could be for a number of reasons, for example, inappropriate dose regimens and use of patients at low risk of developing the disease in prospective trials. Expression of COX-2 can be interrupted by a multitude of agents, including non-selective COX-2 inhibitors such as aspirin, and also other selective COX-2 inhibitors. Many experimental studies have indicated COX-2 suppression with these agents as a means of cancer treatment or prevention to be theoretically possible, although there are issues with dosages required, treatment duration and whether tumours can eventually “escape” from COX-2 inhibition. A repeat of this study with a larger number of patients and a safer method of COX-2 inhibition (for example, lower dose of agent or use of a non-selective inhibitor, e.g. aspirin), together with a placebo arm, would give more useful information. Int J Colorectal Dis (2009) 24:863 DOI 10.1007/s00384-009-0685-3