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Epidemiological studies have found that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk of colorectal cancer (CRC). Cyclooxygenase (COX)-2 expression is present in colorectal cancer and overexpression is associated with metastases and poorer prognosis in multivariate analysis. NSAID treatment results in a reduction of the incidence of colorectal adenoma in patients with familial adenomatous polyposis, in patients with a history of colorectal adenomas and in patients with a history of CRC. Pre-clinical research shows that COX-2 expression is associated with cell proliferation, angiogenesis, apoptosis inhibition and local immune-down modulation. An anticarcinogenic effect has been shown specifically in selective COX-2 inhibitors in animal models. Selective COX-2 inhibitors have fewer adverse effects than the non-selective NSAIDs and are promising chemopreventative and chemotherapeutical agents. The effects of selective COX-2 inhibition in the prevention of and treatment for colorectal carcinoma will be investigated in clinical randomized multicentre trials.

On the Dutch market soon the first COX-2-selective NSAID's will become available. Because these agents selective inhibit the isoenzyme that is involved in inflammation, these drugs will show a better effectiveness/safety ratio, compared to classic NSAID's. In this article we present the current insights on COX-2-NSAID's.

Epidemiological studies have found that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk of colorectal cancer (CRC). Cyclooxygenase (COX)-2 expression is present in colorectal cancer and overexpression is associated with metastases and poorer prognosis in multivariate analysis. NSAID treatment results in a reduction of the incidence of colorectal adenoma in patients with familial adenomatous polyposis, in patients with a history of colorectal adenomas and in patients with a history of CRC. Pre-clinical research shows that COX-2 expression is associated with cell proliferation, angiogenesis, apoptosis inhibition and local immune-down modulation. An anticarcinogenic effect has been shown specifically in selective COX-2 inhibitors in animal models. Selective COX-2 inhibitors have fewer adverse effects than the non-selective NSAIDs and are promising chemopreventative and chemotherapeutical agents. The effects of selective COX-2 inhibition in the prevention of and treatment for colorectal carcinoma will be investigated in clinical randomized multicentre trials.

Acetylsalicylic acid was recently shown to inhibit the development of colorectal adenomas in subjects with a moderately increased risk for colorectal cancer. The mechanisms by which acetylsalicylic acid and other NSAIDs, including COX-2 inhibitors, exert this effect include: inhibition of COX-2, induction of apoptosis and induction of the P21 protein that controls the development of crypt cells. For the majority of the population, a healthy lifestyle and healthy eating habits are the best means of preventing colorectal cancer. In addition, population-wide screening should be encouraged. For people with an increased risk of colorectal cancer, acetylsalicylic acid only has a partial effect and therefore endoscopic surveillance is still indicated. Sulindac or celecoxib may be useful for patients with familial adenomatous polyposis and in particular for inhibiting the development of rectal adenomas after subtotal colectomy with ileorectal anastomosis. However, in these cases endoscopic surveillance is also still necessary.

On the Dutch market soon the first COX-2-selective NSAID's will become available. Because these agents selective inhibit the isoenzyme that is involved in inflammation, these drugs will show a better effectiveness/safety ratio, compared to classic NSAID's. In this article we present the current insights on COX-2-NSAID's.

The efficacy and the adverse effects of non-steroid anti-inflammatory drugs (NSAIDs) are related mostly to inhibition of cyclo-oxygenase (COX), the main enzyme in prostaglandin synthesis. There are two isoenzymes: COX-1, mostly involved in the production of prostaglandins that are important for the normal function of the organism, such as protection of the stomach, vascular homeostasis and kidney function, and COX-2 which is induced by proinflammatory stimuli and is mostly present in inflammatory cells. Conceivably, the COX-1 and COX-2 functions are not separated very strictly. For instance, COX-2 may also come to expression as a reaction to physiological stimuli not connected with an inflammation. It is not yet clear how COX-2 selectivity can best be assessed. The degree of selectivity depends among other things on the test used and the time interval after which the activity is read. Because of the variable findings it is important to rank different NSAIDs on the basis of one and the same test. Use of NSAIDs that mostly inhibit COX-2 appears to result in reduction of the risk of gastric ulcer development. It is to be expected that the selective COX-2 inhibitors now being developed will make the use of NSAIDs even safer.