The impact of anti-inflammatory agents on the outcome of patients with colorectal cancer

Although there is increasing appreciation of the role of the host inflammatory response in determining outcome in patients in colorectal cancer, there has been little concerted effort to favourably manipulate cancer-associated inflammation, either alone or in combination with current oncological treatment. Epidemiological and cardiovascular disease studies have identified aspirin, other nonsteroidal anti-inflammatory drugs and statins as potential chemotherapeutic agents which may manipulate the host inflammatory response to the benefit of the patient with cancer. Similarly, evidence of a chemotherapeutic effect of histamine-2 receptor antagonists, again mediated by an immunomodulatory effect, has previously led to increased interest in their use in gastrointestinal cancer. Extensive pre-clinical data and a limited number of clinical investigations have proposed a direct effect of these agents on tumour biology, with an anti-tumour effect on several of the hallmarks of cancer, including proliferative capacity, evasion from apoptosis and cell cycle regulation, and invasive capability of tumour cells. Furthermore, clinical evidence has suggested a pertinent role in down-regulating the systemic inflammatory response whilst favourably influencing the local inflammatory response within the tumour microenvironment. Despite such compelling results, the clinical applicability of nonsteroidal anti-inflammatory drugs, statins and histamine-2 receptor antagonists has not been fully realised, particularly in patients identified at high risk on the basis of inflammatory parameters. In the present review, we examine the potential role that these agents may play in improving survival and reducing recurrence in patients with potentially curative colorectal cancer, and in particular focus on their effects on the local and systemic inflammatory response.