Capecitabine Demonstrates Improved Survival Benefits Over 5-Flurouracil In The Setting Of Neo-Adjuvant Chemo-Radiation For Locally Advanced Rectal Cancer Patients

In patients with locally advanced rectal cancer, the addition of intravenous fluorouracil (FU) based chemotherapy to preoperative long course radiotherapy significantly increased local control compared to radiotherapy alone. Capecitabine (Cape), an oral prodrug of FU, has been shown to be at least non-inferior to FU in patients receiving neo-adjuvant chemo-radiation (NACRT) followed by surgery and adjuvant chemotherapy. Although, the benefit of adjuvant chemotherapy in this population is unclear, Cape or 5FU with or without oxaliplatin is generally prescribed post-operatively. Our objectives were to identify the differences in pathological complete response rates (pCR) and survival in relation to the chemotherapy component of NACRT for locally advanced (clinical Stage II and III) rectal cancer. We also assessed the benefit of different adjuvant chemotherapy regimens in terms of survival benefits in this patient population. Rectal cancer patients treated at our center between 2010 and 2016 were included in the study. All patients who completed curative intent NACRT were identified. The post-operative pathology, as well as follow-up outcomes were evaluated and analyzed for differences in relation to the neo-adjuvant and adjuvant chemotherapy regimen. This study included 494 patients who completed NACRT followed by surgery. 298 (60.3%) patients received 5FU and 196 (39.7%) patients received Cape based NACRT. 55.7% of the patients completed adjuvant chemotherapy. No difference in pCR rates were noted with regards to neo-adjuvant 5FU vs Cape (HR = 1.230, CI 0.770-1.965, p = 0.386) and at a median follow-up of 5 years, no statistical difference in local control was also noted (HR = 0.906, CI = 0.324-2.535, p = 0.851). However, Cape based NACRT showed improved Disease Specific Survival (DSS) when compared to 5FU in both univariate (HR = 2.748, CI = 1.430-5.282, p = 0.002) and multivariate analysis (HR = 3.8263, CI = 1.529-6.964, p = 0.002). Adjuvant chemotherapy was not associated with a better overall DSS in either univariate (HR = 0.901, CI = 0.472-1.723, p = 0.753) or multivariate analysis (HR = 1.301, CI = 0.602-2.812, p = 0.504) nor was there benefit observed, based on pathological stage or regimen used, on sub-group analysis. Our study reports on the DSS benefit of Cape over 5FU for NACRT. Furthermore, Cape appears to show a benefit even when taking into consideration other disease and treatment related parameters. Our study was unable to identify a benefit in the use of adjuvant chemotherapy in our patient population.