Neoadjuvant chemoradiotherapy (CRT) is the standard of treatment for locally advanced rectal cancer, but it delays administration of systemic chemotherapy, leading to high incidence of distant metastases. To enhance systemic chemotherapy and avoid the damage of radiation, neoadjuvant chemotherapy regimens were under investigation. Here, we aimed to compare the efficacy of preoperative chemotherapy with mFOLFOXIRI alone versus chemoradiotherapy in locally advanced rectal cancer.
Prospectively maintained databases of patients from two clinical trials (NCT01211210 and NCT02217020) underwent preoperative treatment for locally advanced rectal cancer in a single center were included. Those had received standard CRT or mFOLFOXIRI chemotherapy alone preoperatively were selected for this study. All patients had undergone total mesorectal excision. A comparative analysis was performed after the implementation of propensity score matching on the 2 main cohorts (mFOLFOXIRI and CRT).
A total of 142 patients were included in the study, with median age of 51 years old. After propensity score matching, 71 patients were comparable in the two groups. Comparable pathologic complete response (pCR) rate (15.5% vs. 12.7%, P = 0.63) and tumor downstaging rate (42.3% vs. 36.6%, P = 0.49) were observed in the mFOLFOXIRI group and CRT group, respectively. The anal preservation rate was similar between the two groups (87.3% vs. 88.7%, p = 0.79). But lower incidence of anastomotic fistula (7.0% vs. 19.7%, P = 0.026) was shown in mFOLFOXIRI alone group than that of CRT group. And radiation-related dermatitis or proctitis was occurred in 41.7% of patients in the CRT group.
Preoperative mFOLFOXIRI alone showed similar early efficacy in terms of pCR rate and tumor downstaging rate when comparing with CRT, and led to less toxicity and fewer postoperative complications. But this finding requires further analysis from long-term survival data. The phase III study comparing FOLFOXIRI with CRT is ongoing.
Clinical trial identification
This study included two prospective clinical trials NCT01211210 (FOWARC study) and NCT02217020 (FORTUNE study).
Legal entity responsible for the study
All authors have declared no conflicts of interest.