Pilot Study of Neoadjuvant Chemoradiotherapy with Three Cycles of 5-Fluorouracil Plus Leucovorin for Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Neoadjuvant concurrent chemoradiotherapy combined with total mesorectal excision is the main treatment for patients with locally advanced rectal cancer (LARC). However, because distant metastasis remains the major challenge in the management of LARC, we proposed an additional one cycle of chemotherapy before surgery to improve systemic control. METHODS: One hundred sixty-eight patients with clinical stage II and III rectal cancer were enrolled at Kyungpook National University Medical Center (Daegu, Korea) between January 2011 and December 2013 and were considered the study group. In addition, 160 patients were retrospectively reviewed as the historical control group. All the patients underwent total mesorectal excision at 8 weeks after completing the radiotherapy and receiving a total of six cycles of 5-fluorouracil plus leucovorin. RESULTS: Overall, 155 (96.9%) of the 168 patients completed their planned six cycles of study treatment. Dose modification at any cycle was observed in 18 patients (10.7%). The grade 3 to 4 treatment-related toxicity rate was 27.3%, and the most common grade 3 to 4 hematologic adverse event was neutropenia. With a median follow-up duration of 38 months, the estimated 3-year disease-free survival and OS rates were 79.5 and 86.9%, respectively. CONCLUSIONS: Adding one cycle of chemotherapy during the resting period between chemoradiotherapy and surgery was found to be feasible in patients with LARC in terms of the chemotherapy-related adverse events and postoperative complications. These results warrant further investigation in future prospective randomized trials.