Meeting
2019 ASCO Annual Meeting
A multicenter randomized phase III trial of capecitabine with or without irinotecan driven by UGT1A1 in neoadjuvant chemoradiation of locally advanced rectal cancer (CinClare).
Authors
Zhen Zhang
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
Zhen Zhang , Xinchen Sun , Anwen Liu , Yuan Zhu , Yaqun Zhu , Tao Zhang , Jianhui Jia , Shisheng Tan , Junxin Wu , Juying Zhou , Xin Wang , Jialin Yang , Yuanyuan Zhao , Hongyan Zhang , Chen Zhang , Gang Cai , Ji Zhu
Organizations
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Jiangsu Provincial People’s Hospital (The First Affiliated Hospital of Nanjing Medical University), Nanjing, China, 2nd Affiliated Hospital of Nanchang University, Nanchang, China, Zhejiang Cancer Hospital, Hangzhou, China, Department of Radiotherapy and Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, Liaoning Cancer Hospital and Institute, Shenyang, China, Guizhou Provincial Hospital, Guiyang, China, Fujian Cancer Hospital, Fuzhou, China, 1st Affiliated Hospital of Soochow University, Suzhou, China, West China Hospital Sichuan University, Chengdu, China, Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, The Affiliated Hospital of Qingdao University, Qingdao, China, Anhui Provincial Hospital, Hefei, China, Ningbo No.2 Hospital, Ningbo, China, Shanghai Ruijin Hospital, Shanghai, China
Research Funding
Other Foundation
Background: Our phase I/II study identified irinotecan dose differentiated by UGT1A1 genotype in the neoadjuvant CRT and showed improved pCR. The objective of this phase III study was to further investigate irinotecan combined with capecitabine-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Methods: We underwent a prospective, randomized, open-label, multicenter, phase 3 trial in China from Nov.2015 to Dec.2017. Eligible patients with clinical stage T3-4 and/or N+ rectal adenocarcinoma were randomly allocated to two arms. The approach in control arm (Arm A, n = 180) was pelvic radiation of 50 Gy/25 fractions with concurrent capecitabine 825 mg/m2 twice daily 5 days per week, followed by a cycle of XELOX two weeks after the end of CRT. The experimental arm (Arm B, n = 180) was pelvic radiation with capecitabine 625 mg/m2 twice daily 5 days per week and combined with weekly irinotecan. The irinotecan dose was used based on UGT1A1 genotype of 80mg/m2 for UGT1A1*1*1 or 65mg/m2 for UGT1A1*1*28 weekly, followed by a cycle of XELIRI. The primary endpoint is pathological complete response (pCR). This trial was registered with ClinicalTrials.gov, number NCT02605265. Results: Surgery was performed in 86.5% and 88.2% of patients in two groups, with 38.9% and 30.5% of patients got abdominoperineal resection respectively. The pCR rate was 17.5% in Arm A and 33.8% in Arm B (P = 0.001). Four and 6 patients maintained a complete clinical response status at least 12 months and were marked as cCR. The CR rate, including pCR and cCR, was 17.4% in Arm A and 33.1% in Arm B (P = 0.001). The most common grade 3-4 adverse events during preoperative treatment were leucopenia (3.4% vs. 25.3%), neutropenia (1.7% vs. 19.7%) and diarrhea (1.7% vs. 13.5%) in two arms. The overall rate of surgical complications were not significantly different between arms (11.0% vs. 14.6%). Conclusions: Adding irinotecan guided by UGT1A1 to capecitabine-based neoadjuvant chemoradiotherapy significantly increases complete tumor response. The treatment toxicities were increased but tolerable. This treatment can be as an option for ‘watch and wait’ approach. Clinical trial information: NCT02605265
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Abstract Details
Session Type
Poster Discussion Session
Session Title
Gastrointestinal (Colorectal) Cancer
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Colorectal Cancer–Local-Regional Disease
Clinical Trial Registration Number
NCT02605265
Citation
J Clin Oncol 37, 2019 (suppl; abstr 3510)
DOI
10.1200/JCO.2019.37.15_suppl.3510
Abstract #
3510
Poster Bd #
2
Abstract Disclosures
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