Adjuvant Concurrent Uracil-Tegafur with Leucovorin and Radiotherapy for Locally Advanced Rectal Cancer

Abstract

Purpose: This prospective, nonrandomized study was conducted to test the efficacy and toxicity of adjuvant concurrent chemoradiation therapy (CCRT) using uracil-tegafur (UFUR) and leucovorin (LV) in patients with locally advanced rectal cancer. Material and Methods: From February 2001 through November 2004, 17 patients with stage II or III rectal adenocarcinoma were enrolled in the study. All underwent curative resection followed by adjuvant CCRT at Mackay Memorial Hospital, Taipei. The median age was 54 (range, 42 to 86) years. The operative procedures were either abdominoperineal resection or a radical proctectomy. Radiotherapy (RT), delivered in 28 to 33 fractions, consisted of 45Gy of whole-pelvis irradiation followed by a 5.4 to 14.4Gy local boost to the tumor bed. A combination of oral UFUR at 200 to 250 mg/m2/day and LV 45 to 60 mg/day was given 7 days a week during the RT course and then for at least one year or until treatment failure, whichever came first. Results: Of the 17 patients, 7 were male and 10 were female. Five had undergone APR and 12 RP. The adenocarcinoma was moderately differentiated in 15 poorly differentiated in 2. The median radiation dose was 59.4 (range, 50.4 to 59.4)Gy, with a mean 57.7Gy. None of the patients died during the CCRT course. The median survival for all 17 patients was 36 months, and the 3-year overall survival was 68%. The 3-year disease-free survival rate was 44%. Four patients developed local failure, yielding a 3-year local control rate of 68%. Five patients developed distant metastasis, for a 3-year metastasis-free rate of 62%. The most-common side effects were diarrhea and nausea or vomiting, dermatitis, fatigue, and hematological toxicity consisting of anemia, leucopenia, and thrombocytopenia. No grade 4 toxicity was observed. Three patients had grade 3 diarrhea, and 1 grade 3 fatigue and vomiting, but these were tolerable. None had greater than grade 2 skin toxicity. One patient had grade 3 anemia, but none had grade 3 leucopenia or thrombocytopenia. Conclusions: Adjuvant CCRT that includes oral UFUR and LV provided acceptable survival and local control rates with acceptable toxicity in patients with locally advanced rectal cancer. A randomized trial of this combined treatment is warranted.