A clinical study to evaluate the toxicities of adjuvant chemoradiotherapy in early stage after low-anterior resection for locally advanced rectal cancer

Objective: In the previous study completed in Korea, early three-dimensional conformal radiotherapy concurrent with chemotherapy in rectal cancer after radical surgery demonstrated a better prognosis compared with late radiotherapy. However, with the report of MOSAIC trial, the adjuvant chemotherapy regimen had transferred from 5-Fu alone to combined 5-Fu and Oxaliplatin. We need more evidence to clarify the best radiotherapy timing during the whole period of adjuvant therapy . Methods: Patients who met the following criteria were accrued in this study: 18-70 years old, lower anterior resection,pathologically proven rectal adenocarcinoma, stage T3-4 and/or N +, no evidence of distant metastases and KPS ≥70. Three dimensional conformal Radiotherapy was started at the fourth week after surgery, which included 45 Gy whole pelvic radiation following by 6-10 Gy tumor bed boost. Oxaliplatin of 50 mg/m2 weekly and Xeloda 625 mg/m2 twice a day, every week from d1-5 were used concurrent with radiotherapy. Toxicity was evaluated and graded by common toxicity critera version 3.0. The study was designed as Simon two-phase design, in the first phase, a total of 15 patients were accrued, and if more than or equal to 9 patients had grade 3 toxicity, we had 85% power to confirm the toxicity caused by early radiotherapy more than 50%. Otherwise, another 15 patients of the second phase were accrued, we would have 85% power to confirm the high toxicity of more than 50% if 18 out of 30 patients had grade 3 toxicity. Results: From July 2008 to December 2008, 15 patients were treated with early radiotherapy concurrent with combined chemotherapy, Grade 3 gastrointestinal toxicity occurred in 12 patients and Grade 3 hematologic toxicity occurred in 2 patients. According to Simon design, we had 85% power to confirm the toxicity caused by early radiotherapy more than 50%. Conclusions: For locally advanced rectal cancer patients, whole pelvic radiotherapy concurrent with Oxaliplatin and Xeloda had severe toxicities. Further studies are needed to decrease toxicities. (authors)