The Impact of Chemotherapy Completion on the Efficacy of Irinotecan in the Preoperative Chemoradiotherapy of Locally Advanced Rectal Cancer: An Expanded Analysis of the CinClare Phase III Trial

Abstract

BackgroundThis study explored the impact of chemotherapy completion on irinotecan efficacy in preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Patients and MethodsPatients with locally advanced rectal cancer (T3/4 and/or LN+) receiving neoadjuvant chemoradiotherapy were enrolled. All received preoperative pelvic radiotherapy concurrently with capecitabine and irinotecan, followed by a course of XELIRI and surgery. Patients were divided into low- and high-completion groups based on their cycles of concurrent irinotecan (1-3 or 4-5). Tumor response was compared. Significant risk factors for low completion were investigated by logistic regression modeling then a predictive nomogram was built. ResultsOverall, 371 patients were enrolled, with 102 patients from CinClare phase III trial (NCT02605265). Proportions of patients with low and high completion were 38.8% and 61.2%, respectively. In the general population, the complete tumor response rates (combining sustained clinical complete response and pathologic complete response) were 21.5% and 33.6% in the low- and high-completion groups, respectively (P = .02), which were 24.2% versus 43.5% in the CinClare group (P = .08). The pathologic complete response rates were 19.4% and 26.1%, respectively (P = .19). A predictive nomogram was established and 3 different risk groups (low, intermediate, and high risk) were identified, with high completion rates of 29.2%, 50.0%, and 68.9%, respectively (P < .0001). ConclusionOur analysis suggested higher completion of concurrent irinotecan was associated with better tumor response for patients with locally advanced rectal cancer with UGT1A1∗1∗1 or UGT1A1∗1∗28 phenotypes in the neoadjuvant setting, and at least 4 cycles was recommended.