Abstract
BackgroundPreoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT.MethodsPatients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.ResultsFrom September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9–83.6) and 73.4% (95% CI 58.7–83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414–1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable.ConclusionWe demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.Trial registrationDate of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J
Highlights
Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects
In a meta-analysis performed by Camma et al, who compared surgery alone with preoperative RT, the latter was associated with significantly prolonged survival durations and higher cancer-specific survival rates and significantly reduced local recurrence rates [4]
Bosset et al reported 5 year local recurrence rates of 10.9 and 10.7% and 5 year distant recurrence rates of 32.1 and 29.8% in the CRT and CRT + adjuvant chemotherapy arms, respectively [14]. These results suggest that the suppression of distant metastasis is important for improving the survival of patients with locally advanced rectal cancer (LARC)
Summary
Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. Based on the results of those clinical studies, Western guidelines recommend the use of preoperative RT or CRT for T3/T4 or N+ middle or low rectal cancer [8, 9] These preoperative treatments significantly improve local recurrence rates, no improvements in survival have been observed [10,11,12,13]. Bosset et al reported 5 year local recurrence rates of 10.9 and 10.7% and 5 year distant recurrence rates of 32.1 and 29.8% in the CRT and CRT + adjuvant chemotherapy arms, respectively [14] These results suggest that the suppression of distant metastasis is important for improving the survival of patients with locally advanced rectal cancer (LARC). A recent phase III trial examined the potential for the elimination of RT due to the effects of preoperative chemotherapy [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
