Prospective phase Ⅱ study of neoadjuvant chemoradiotherapy followed by chemotherapy in locally advanced rectal cancer

Objective: To evaluate the efficacy and safety of adding neoadjuvant chemotherapy following neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Methods: A total of 80 patients confirmed with locally advanced rectal cancer were enrolled during January 2012 and December 2015 in Guizhou Medical University Affiliated Cancer Hospital and were randomized with the method of lottery into the experimental group and the control group. In the experimental group, 40 patients received 4 cycles of FOLFOX4 after chemoradiotherapy and then had total mesorectal excision (TME). Another 4 cycles of FOLFOX4 were administered after surgery. In the control group, 40 patients had TME surgery 6-8 weeks after chemoradiotherapy and received 8 cycles of FOLFOX4 as adjuvant chemotherapy. Pelvic radiotherapy dose was 50 Gy in 25 fractions, 5 days per week for 5 weeks. 5-Fu continuous infusion was administered throughout radiotherapy. The pCR rate, downstaging rate, R₀ resection rate, local recurrence rate, distant metastasis rate, survival rate, incidence of toxicities, surgical complications and completion of treatment were observed. Results: The pCR rate was 20.0% in the experimental group and 5.0% in the control group (χ² = 4.114, P < 0.05). The downstaging rate was 77.4% in the experimental group and 55.6% in the control group(P > 0.05). No statistically significant difference was observed in R₀ resection rate, 3-year local recurrence rate, 3-year distant metastasis rate and 3-year survival rate between the two groups (P > 0.05). Patients in the experimental group had higher completion rate of 8 cycles of systemic chemotherapy (87.1% vs. 61.5%, χ² = 4.985, P < 0.05). No statistically significant difference was observed in acute toxicities and postoperative complications. Conclusions: Adding systemic chemotherapy after neoadjuvant chemoradiotherapy for locally advanced rectal cancer has significantly higher pCR rate and lower toxicities and side events compared with chemoradiotherapy alone. Longer follow-up and larger scale of clinical research are needed. (authors)