Combination of a COX-2 inhibitor with radiotherapy or radiochemotherapy in the treatment of thoracic cancer.

Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin production in pathologic states such as inflammatory processes and cancer. The enzyme is often overexpressed in premalignant lesions and cancer, including cancers of the lung and esophagus. Inhibition of this enzyme with selective COX-2 inhibitors was found to enhance tumor response to radiation in preclinical studies, suggesting that these agents can improve the response of various cancers to radiotherapy. On the basis of these preclinical findings, clinical trials of the combination of celecoxib, a selective COX-2 inhibitor, with radiotherapy were initiated in patients with lung carcinoma and with chemoradiotherapy in patients with esophageal carcinoma. The rationale for using selective COX-2 inhibitors is discussed, and the current clinical protocols and the initial findings are described.