Genotype-driven Phase I Study of Irinotecan Administered in Neoadjuvant Chemoradiotherapy in Patients With Stage II/III Rectal Cancer

Genotype-driven Phase I Study of Irinotecan Administered in Neoadjuvant Chemoradiotherapy in Patients With Stage II/III Rectal Cancer

Irinotecan is one of effective drugs for colorectal cancer. In neoadjuvant chemoradiotherapy (CRT), Irinotecan is prescribed in a low dose of 50mg/m2/week because of toxicity. Some current studies showed that irinotecan's dose can be increased significantly for those patients with 6/6 or 6/7 genotype of UGT1A1. therefore, the investigators designed this trial to explore the maximal tolerable dose (MTD) of Irinotecan in combined neoadjuvant CRT.

Inclusion Criteria:

• Patients with rectal adenocarcinoma
• Clinical staged T3/4 or any node-positive disease
• Age of 18-75 years
• Karnofsky Performance Status > 80
• Adequate bone marrow reserve, renal and hepatic functions
• Without previous antitumoural chemotherapy
• No evidence of metastatic disease
• Written informed consent before randomization
• UGT1A1's genotype of 6/6 or 6/7

Exclusion Criteria:

• Clinical staged I or IV
• Age of <18 or >75 years
• Karnofsky Performance Status < 80
• Previous pelvis radiotherapy
• Previous antitumoural chemotherapy
• Clinically significant internal disease
• Refuse to write informed consent before randomization
• UGT1A1's genotype of 7/7