The impact of completion of chemotherapy on the efficacy of irinotecan in the preoperative chemoradiotherapy of locally advanced rectal cancer: An expanded analysis of the CinClare phase III trial

Abstract Background This study was designed to explore the impact of completion of chemotherapy on the efficacy of irinotecan in preoperative chemoradiotherapy in patients with locally advanced rectal cancer (LARC). Patients and Methods LARC (T3/4 and/or LN+) patients receiving neoadjuvant chemoradiotherapy were enrolled. All patients received preoperative pelvic radiotherapy concurrently with capecitabine and weekly irinotecan (80 or 65 mg/m2/qw for 5 weeks), followed by a course of XELIRI and surgery. Patients were divided into a low-completion group (1∼3 cycles) and a high-completion group (4∼5 cycles) based on their actual cycles of concurrent irinotecan. The tumor response was compared between the groups. Significant risk factors for low completion were investigated by logistic regression modeling and were selected to build a predictive nomogram. Results A total of 371 patients were enrolled, with 102 patients from the CinClare phase III trial (NCT02605265). The proportions of patients with low- and high-completion were 38.8% and 61.2%, respectively. In the general population, the rate of complete tumor response combining complete pathological and clinical responses was 21.5% in the low-completion group versus 33.6% in the high-completion group (P=0.02), which was 24.2% versus 43.5% in the CinClare group (P=0.08). A predictive nomogram was established, and three different risk groups (low-, intermediate- and high-risk) were identified, with high completion rates of 29.2%, 50.0% and 68.9%, respectively (P Conclusion Our analysis suggested that higher completion of concurrent irinotecan was associated with a better tumor response for LARC patients in the neoadjuvant setting, and at least four cycles are recommended.