Preoperative Oxaliplatin, Capecitabine, and External Beam Radiotherapy in Patients with Newly Diagnosed Primary Operable, cT3NxMo, Low Rectal Cancer A Phase II Study

Purpose: In patients with locally advanced rectal cancer (LARC), preoperative chemoradiation is known to improve local control, and down-staging of the tumor serves as a surrogate for survival. Intensification of the systemic therapy may Lead to higher down-staging rates and, thus, enhance survival. This phase II study investigated the efficacy and safety of preoperative capecitabine and oxaliplatin in combination with radiotherapy. Patients and Methods: Patients with LARC of the mid and lower rectum, T3NxMO staged by MRI received radiotherapy (total dose 45 Gy) in combination with oral capecitabine (825 mg/m(2) twice a day on radiotherapy days; weeks 1-4) and oxaliplatin 50 mg/m2 intravenously (days 1, 8, 15, and 22). Efficacy was evaluated as rate of tumor down-categorization at the T level. Results: A total of 59 patients were enrolled (19 women, 40 men; median age of 61 years) and all were evaluable for efficacy and toxicity. Down-categorization at the T level was observed in 53% with pathological complete response in 6 patients (10%). Actual total radiotherapy, oxaliplatin and capecitabine doses received were 97%, 90%, and 93% of the protocol-specified preplanned doses, respectively. Grade 3/4 toxicity was observed in 15 patients (25%). The most frequent was diarrhea (12%). Conclusions: Preoperative chemoradiation with capecitabine and oxaliplatin is feasible in patients with MRI-proven cT3 LARC. The only clinically relevant toxicity was diarrhea. Overall, efficacy of the multimodality treatment was good, but not markedly exceeding that of 5-FU- or capecitabine-based chemoradiation approaches.