174PD - A randomized phase III trial of capecitabine with or without irinotecan driven by UGT1A1 in neoadjuvant chemoradiation of locally advanced rectal c...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Gastrointestinal tumours
Topics Cytotoxic agents
Rectal Cancer
Surgical oncology
Presenter Tao Zhang
Citation Annals of Oncology (2016) 27 (suppl_9): ix53-ix67. 10.1093/annonc/mdw581
Authors T. Zhang1, J. Zhu2, J.Y. Chen3, Y. Zhu4, J. Zhou5, Y. Zhu6, J.H. Jia7, C. Zhang8, X. Wang9, Y.H. Gao10, G. Cai11, B. Luo12, J. Wu13, A. Liu14, B. Xu15, Z. Zhang2
  • 1Department Of Oncology, 1st Affiliated Hospital of Chongqing Medical University, 400016 - Chongqing/CN
  • 2Department Of Radiation Oncology, Shanghai Cancer Center Fudan University, 1 - Shanghai/CN
  • 3Department Of Oncology, Jiangsu Provincial People’s Hospital (The First Affiliated Hospital of Nanjing Medical University), 1 - Nanjing/CN
  • 4Department Of Oncology, 2nd Affiliated Hospital Suzhou (Soochow) University, 1 - Suzhou/CN
  • 5Department Of Oncology, 1st Affiliated Hospital of Suzhou (Soochow) University, 1 - Suzhou/CN
  • 6Department Of Oncology, Zhejiang Cancer Hospital, 1 - Hangzhou/CN
  • 7Department Of Oncology, Liaoning Cancer Hospital & Institute, 1 - Shenyang/CN
  • 8Department Of Radiation Oncology, Ningbo No.2 Hospital, 1 - Ningbo/CN
  • 9Department Of Radiation Oncology, West China Hospital, Huaxi, Sichuan University, 1 - Chengdu/CN
  • 10Department Of Radiation Oncology, Cancer Centre Sun Yat-Sen University, 1 - Guangzhou/CN
  • 11Department Of Radiation Oncology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University, College of Medicine, 1 - Shanghai/CN
  • 12Department Of Radiation Oncology, Hubei Province Tumor Hospital, 1 - Wuhan/CN
  • 13Department Of Radiation Oncology, Fujian Provincial Cancer Hospital, 1 - Fuzhou/CN
  • 14Department Of Radiation Oncology, 2nd Affiliated Hospital of Nanchang University, 1 - Nanchang/CN
  • 15Department Of Radiation Oncology, Fujian Medical University Union Hospital, 1 - Fuzhou/CN



Early small sample size trials have assessed the addition of irinotecan to standard neoadjuvant CRT in rectal cancer. All patients in case group in ARISTOTLE trial were prescribed with weekly irinotecan dose of 60mg/m2 for four times. In our previous phase I trial, the weekly dose of irinotecan was escalated to 65mg/m2 and 80mg/m2 guided by UGT1A1*28 genetypes in neoadjuvant CRT. Therefore, this phase III trial was designed to confirm the potential improvement in outcomes seen with the addition of irinotecan to CRT.


Patients are randomly allocated to either RT 50 Gy with concurrent capecitabine, followed by a cycle of XELOX two weeks after the end of CRT (Control arm) or RT 50 Gy with concurrent capecitabine and irinotecan, followed by a cycle of capecitabine and irinotecan (Case arm). Capecitabine is prescribed with 825mg/m2 twice daily from first day of RT and given 5 days per week during RT in control group. In the other group, capecitabine dose is 625mg/m2 twice daily and additional weekly irinotecan dose is 80mg/m2 or 65mg/m2 guided by UGT1A1*28 genetypes . Surgery is schedule 8 weeks after the end of CRT, then, five cycles of XELOX are recommended during the course of adjuvant chemotherapy. The primary end point is ypCR. The hypothesis is to increase ypCR from 12% in the control group to 25% in the case group. To detect such a difference, with alpha=0.05 (two-tailed) and belta=0.15, 360 randomly assigned patients are required. Secondary end points are toxicities, surgical complications, local control, progression-free survival and overall survival.


A total of 121 patients participated in this study from November 2015 to July 2016. The cases were divided into A group(60) and B group (61) randomly. At the analysis time, 25 patients in each group were underwent surgery. The number of cases got pCR was 5(20%) and 12(48%), respectively. Toxic effects and treatment compliance datas have been collected.


It is estimated that the study will be completed in September 2017.The tolerability and higher efficacy of the therapy in patients with local advanced rectal cancer treated by neoadjuvant CRT combining with the irinotecan will be evaluated.

Clinical trial indentification

NCT02605265, released on December 24, 2015

Legal entity responsible for the study

T. Zhang


Fudan University Shanghai Cancer Center,


All authors have declared no conflicts of interest.