Purpose: Capecitabine is an attractive radiosensitizer which can be tumor specific. This study was undertaken to evaluate the toxicity and efficacy of oral capecitabine when used with preoperative radiation therapy.
Methods and materials: We conducted a prospective Phase II trial to assess the pathologic response, sphincter preservation effect, and acute toxicity of preoperative chemoradiation (CRT) in locally advanced (uT3-4/N +) but resectable adenocarcinoma of the lower two-thirds of the rectum. The radiation dose was 50 Gy over 5 weeks (46 Gy to whole pelvis + 4 Gy boost), and capecitabine was administered daily at a dose of 1650 mg/m(2) during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision 4 to 6 weeks after completion of CRT and followed by four cycles of capecitabine (2500 mg/m(2)/day for 14 days).
Results: Ninety-five patients were entered into this study; their median age was 55 (range, 31-75 years). Ninety (95%) patients completed preoperative CRT as planned, and complete resection was achieved in 92 of 94 resected cases (98%). Downstaging rate was 71% (56/79) on endorectal ultrasonography, and it was 76% (71/94) on pathology finding. No tumor cell was observed in the specimens of 11 patients (12%). Among the 54 whose tumor was located within 5 cm from the anal verge, 40 patients (74%) underwent sphincter-preserving procedures. Elevation of the distal tumor margin from the anal verge by preoperative CRT was 0.8 +/- 1.3 cm. Grade 3 toxicities were rare (diarrhea in 3% and neutropenia in 1%).
Conclusion: Preoperative CRT using capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation with a low toxicity profile.