Comparing pathological complete response rate using oral capecitabine versus infusional 5-fluorouracil with preoperative radiotherapy in rectal cancer treatment.

BACKGROUND: Infusional 5-fluorouracil (5-FU) has been the standard radiation sensitizer in patients undergoing preoperative long-course chemoradiotherapy (CRT) for locally advanced rectal cancer in Australia. Capecitabine (Xeloda) is an oral 5-FU prodrug of comparable pharmacodynamic activity, currently preferred in place of 5-FU infusion, its established counterpart in neoadjuvant CRT for rectal cancer. The few studies quantifying pathological complete response (pCR) of Xeloda versus 5-FU have produced inconsistent results. We reviewed our own data to determine if the rates of pCR of oral capecitabine were non-inferior to intravenous 5-FU in patients undergoing neoadjuvant CRT for rectal cancer.

METHODS: A retrospective study was performed from a prospectively kept database. Four hundred and fifty-two patients received preoperative CRT from January 2006 to January 2016. Pelvic radiotherapy was delivered concurrently with capecitabine (n = 42) or infusional 5-FU (n = 341). The remaining received different chemotherapy regimens. Surgery was performed 6-12 weeks of CRT completion. Pathological responses were assessed using Dworak regression grading score (0-4). Clinical outcomes were evaluated in terms of local control and recurrence-free survival.

RESULTS: The proportion of patients who had a tumour regression score of 4 (pCR) after CRT was 4/42 (9.5%) in the capecitabine group and 71/341 (20%) in the infusional 5-FU group (P = 0.082). pCR was an independent predictor for survival in this group of patients (hazard ratio: 0.002, P = 0.0001, 95% confidence interval: 0.0001-0.027).

CONCLUSION: The use of capecitabine as neoadjuvant chemotherapy in patients with rectal cancer was associated with a reduced rate of pCR. However this difference did not achieve statistical significance.