Possible Protective Effect of Celecoxib Against Capecitabine Induced Hand and Foot Syndrome in Patients With Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of malignancy-related mortality. Capecitabine has been approved for the treatment of colorectal cancer as first-line therapy. About 50%-68% of patients who take capecitabine develop Hand-foot syndrome. Hand-foot syndrome (HFS) is the most common adverse event of capecitabine-based chemotherapy. Initial symptoms of HFS are dysesthesia, tingling in the palms, fingers, and soles of the feet, and erythema, which may progress to an extremely painful and debilitating condition without prompt management. These symptoms can potentially lead to a worsened quality of life in patients taking capecitabine-based chemotherapy. Moreover, the adverse reaction necessitates dose-reduction or withdrawal of the chemotherapeutic agent. The mechanisms of HFS are still unknown, and there are limited data available on how to prevent them or manage them. However, different hypotheses of capecitabine-induced HFS pathogenesis have been suggested. One of the hypotheses stated that HFS is a kind of inflammation mediated by cyclooxygenase's (COX-2) over expression in palm and feet by capecitabine and its metabolites causing elevation of inflammatory markers as tumor necrosis factor alpha (TNF-α). COX-2 enzyme plays a main role in inflammation and pain. Therefore, celecoxib which is selective (COX-2) inhibitor may have a key role in the HFS treatment plan. A retrospective study and two prospective studies showed that combining capecitabine with celecoxib, a selective COX-2 inhibitor, can significantly reduce capecitabine-related HFS in colorectal cancer patients. Those studies were dependent on HFS grading only without measuring any markers. So, in our study we assess possible protective effect of celecoxib against capecitabine induced HFS and measure inflammatory marker as tumor necrosis factor alpha (TNF-α), oxidative stress marker as Malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) enzyme to show whether capecitabine induced HFS is caused by COX-2 mediated inflammation or not.