Systemic inflammation, cachexia and prognosis in patients with cancer

Abstract

Cachexia remains an important cause of morbidity and mortality among cancer patients. The mechanisms underlying this syndrome remain unclear and are almost certainly multifactorial. Evidence from animal models suggests a compelling link between cachexia and inflammation, and a variety of pro-inflammatory cytokines play an integral role. This review summarizes current thinking relating to inflammation, cachexia and prognosis in cancer patients, with particular emphasis on studies relating to recent therapeutic advances. Pro-inflammatory cytokines induce the acute phase protein response, a key marker of systemic inflammation. Recent evidence has also implicated other tumour-derived mediators, such as proteolysis-inducing factor and parathyroid hormone-related peptide. In addition, systemic inflammation has been found in association with many malignancies, and has been correlated with weight loss, hypermetabolism, anorexia, and adverse prognosis. Treatments such as fish oil, monoclonal antibodies, and non-steroidal anti-inflammatory drugs, have all been utilized to attenuate systemic inflammation and influence weight loss. Recent clinical studies have suggested that eicosapentaenoic acid and cyclo-oxygenase 2 inhibitors promote weight gain and downregulate the acute phase protein response. Pro-inflammatory processes are clearly implicated in the hypermetabolism and weight loss associated with cancer-associated cachexia. In addition, the presence of systemic inflammation is now clearly linked with adverse prognosis in patients with cancer, which cannot be fully explained by the association with weight loss. Systemic inflammation remains an important area for novel therapeutic targets in combating cachexia, and eicosapentaenoic acid and cyclo-oxygenase 2 inhibitors appear to be efficacious in the armory against cachexia.