Capecitabine as a radiosensitizing agent in neoadjuvant treatment of locally advanced resectable rectal cancer: prospective phase II trial.

AIM To evaluate the efficacy and toxicity of preoperative chemoradiotherapy with capecitabine in locally advanced rectal cancer. METHODS Between June 2004 and January 2005, 57 patients with operable, clinical stage II-III adenocarcinoma of the rectum entered the prospective phase II study. Radiation dose was 45 Gy (25x1.8 Gy). Concurrent chemotherapy with a daily dose of 1650 mg/m2 capecitabine was administered orally, divided into two equal doses per day, including weekends. Patients were evaluated weekly for acute toxicity and compliance with the protocol. Surgery was scheduled 6 weeks after the completion of the chemoradiotherapy. RESULTS A single female patient died after receiving 27 Gy, because of pulmonary embolism. All other patients completed the preoperative chemoradiotherapy according to the protocol and a definitive operation was performed in all but one of these patients. The complete pathological response was recorded in 5 patients (9.1%). Tumor (T), lymph nodes (N), and overall downstaging rates were 40%, 52.9%, and 49.1%, respectively. Total sphincter preservation rate was 65.5% (36 out of 55 patients) and the rate in 27 patients with tumors located within 5 cm of the anal opening was 37% (10 out of 27 patients). The most frequent side-effect of the combined therapy was dermatitis (grade 3 in 19 patients). After surgery, a single patient died due to sepsis during the early perioperative period. Nonlethal perioperative complications were recorded in 24/55 patients. CONCLUSION Preoperative chemoradiotherapy with oral capecitabine is safe and well tolerated. It has a downstaging potential and can increase the possibility for sphincter preservation surgery.