Elizabeth M. Gore, MD

Overexpression of cyclooxygenase-2 (COX-2) is frequently presentin lung cancer and may play a significant role in carcinogenesis, invasion,and metastasis. It has been associated with shortened survival inpatients with resected early-stage adenocarcinoma of the lung. COX-2inhibition decreases tumor cell proliferation in vivo and has been shownto enhance tumor radiosensitivity. Additionally, COX-2 inhibition mayprotect normal pulmonary tissue from radiation fibrosis. Clinical studiesare under way to assess the potential benefits and risks of COX-2inhibition in the treatment of lung cancer. The rationale for COX-2inhibitors in the treatment of lung cancer will be reviewed. The resultsof a phase II study assessing the acute toxicity of concurrent celecoxib(Celebrex) and thoracic irradiation in patients with non–small-cell lungcancer (NSCLC) are reported, and an ongoing Radiation TherapyOncology Group study using celecoxib and concurrent radiation therapyfor NSCLC in patients with intermediate prognostic factors is reviewed.

Over the past decade, studies have shown improved survival inpatients with locally advanced non–small-cell lung cancer. This can beattributed to better systemic therapy, growing experience with combined-modality therapy, technologic advances allowing for increasedradiation doses, better supportive care, and better patient selection.With longer survival, we are seeing an increase in the incidence ofcentral nervous system (CNS) metastases. Prophylactic cranial irradiation(PCI) decreases the incidence of CNS metastases in these patientsand may have a favorable impact on quality of life and overall survival.This paper reviews the incidence of CNS metastases in non–small-celllung cancer patients, past experience with PCI, and a current studyevaluating the impact of PCI on survival, neuropsychological function,and quality of life.