Esophagitis in combined modality therapy for locally advanced non-small cell lung cancer

Within the last 10 to 15 years, several randomized trials have validated the importance of chemotherapy in the treatment of locally advanced non-small cell lung cancer and have shown that combined modality therapy improves survival compared with radiotherapy alone. Esophagitis appears to be the primary toxicity, with an increased incidence in combined modality trials. Esophagitis is an inflammatory response of the esophageal mucosa. Treatment with chemotherapy or radiotherapy destroys rapidly dividing cells, such as those in the basal epithelial cell layer. Cell death decreases the renewal rate of the basal epithelium, causing mucosal atrophy, ulceration, and initiation of the inflammatory response. Synergy between chemotherapy and radiotherapy may increase the severity and extent of esophagitis observed with combined modality therapy. Based on Radiation Therapy Oncology Group criteria, the incidence of >/=grade 3 esophagitis following radiation therapy alone or combined modality therapy ranges from less than 5% to 53%. Four sequential, multi-institutional phase I or II studies were conducted during the last 5 years to explore the use of paclitaxel in combined modality therapy for patients with non-small cell lung cancer. In the three phase II trials, esophagitis was the main toxicity, with incidences ranging from 17% to 26% using Radiation Therapy Oncology Group criteria. A multivariate analysis identified a statistically significant correlation between esophageal toxicity and both response to therapy and performance status. Other factors, including gender, age, histology, survival, and length of esophagus within the primary and boost radiation field, were not significantly correlated with esophageal toxicity.