Background: This study explored the impact of chemotherapy completion on irinotecan efficacy in preoperative chemoradiotherapy in patients with locally advanced rectal cancer.
Patients and methods: Patients 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.
Results: Overall, 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).
Conclusion: Our 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.
Keywords: Dose-effect relationship; Irinotecan competition; Neoadjuvant chemoradiotherapy; Rectal cancer; pCR.
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