Preoperative chemoradiotherapy using S-1 combined with celecoxib for advanced lower rectal cancer: Phase I/II study

Objectives: To clarify the safety and efficacy of celecoxib combined with chemoradiotherapy using S-1 for lower rectal cancer. Methods: Twenty-one patients with pathologically proven lower rectal adenocarcinoma (cT3-T4, Tx N+, M0) were included in this study. A total dose of 45 Gy was administered in daily fractions of 1.8 Gy. Celecoxib was given orally twice daily with S-1 on the day of irradiation. The dose of celecoxib was set at 400 mg/day. In Phase I, the S-1 dose was started at 80 mg/m(2)/day; in Phase II, S-1 was administered in the same dose as Phase I. Patients underwent surgery six to eight weeks after completing chemoradiotherapy, followed by six months of postoperative adjuvant chemotherapy. Results: The S-1 recommended dose was 80 mg/m(2)/day. The pathological complete remission rate was 15.8%, the rate of protocol completion was 14.3%, and the rate of adverse events exceeding Grade 3 was 19.0%. Surgery was performed in 19 cases, with a sphincter-sparing rate of 31.6%. Postoperative complications exceeding Grade 3 occurred in 52.4% of cases. The three year overall survival and relapse-free survival rates were 89.3% and 67.0%, respectively. Conclusions: We failed to show a synergistic or additive therapeutic effect of preoperative CRT using S-1, combined with celecoxib, for lower advanced rectal cancer beyond CRT using 5 FU or capecitabine alone. The incidence of complications, evidently involving intestinal ischemia, was relatively high. This treatment strategy is not recommended at present.