Cyclooxygenase-2 inhibitors and antioxidants in the treatment of cachexia

Abstract

Cancer cachexia is increasingly becoming a critical component in the comprehensive approach to cancer patients influencing morbidity, mortality and quality of life. Therefore its pathophysiology and the main contributing factors have been investigated with the aim of developing effective therapies. Reported findings highlight the role of chronic inflammation and oxidative stress in the onset of cancer cachexia. Chronic inflammation, one of the main features of cancer cachexia, triggers the overproduction of proinflammatory cytokines playing a major role in the pathogenesis of systemic symptoms of cachexia; therefore, antiinflammatory drugs such as cyclooxygenase-2 inhibitors could break the 'vicious circle' leading to the onset and worsening of this devastating syndrome. Likewise, oxidative stress, almost always accompanying cancer cachexia, may be counteracted by effective antioxidant treatments. The most relevant recent clinical approaches addressing these targets are reported. Fairly advanced clinical data on efficacy of cyclooxygenase-2 inhibitors and antioxidants in advanced cancer patients are promising, but the best way to administer and combine them with other agents, the optimal dose and timing remain uncertain. However, because cachexia is a multifactorial syndrome, therapeutic approaches targeting a single contributing factor may be inadequate. A rational treatment should thus be multitargeted addressing all key contributing factors.