XCHT for Irinotecan-Induced Gut Toxicities (Randomized Controlled Trial)

A total of 98 patients, who are planning to recieve at least 3 cycles of irinotecan chemotherapy, will be randomly assigned, at a 1:1 ratio, to XCHT group or placebo group, using a central randomization system. Patients will be administered with XCHT/placebo (9 g, qd, po) for 5 days each cycle of chemotherapy for 3 cycles. The XCHT/placebo administration begins 3 days before chemotherapy in each cycle, that is the chemotherapy begins on the 4th day of XCHT/placebo administration. Plasma will be collected for pharmacokinetic testing (using raloxifene 60mg po as probe), on the day before chemotherapy, that is on the 3rd day of XCHT/placebo administration in each cycle. The purpose of this study includes 1) to determine the safety and efficacy of XCHT for prevention of irinotecan-induced diarrhea; 2) to determine the PK profile of SN-38, SN-38G, raloxifene, raloxifene-glucuronide, and XCHT components; and 3) to validate the use of raloxifene-4'G as a probe for irinotecan-induced diarrhea.

Inclusion criteria

• Malignant tumor confirmed by histology or cytology;
• Age ≥ 18 years old, ≤ 75 years old;
• ECOG score of the patient ≤ 2 points;
• Patients who have diarrhea worse than grade 2 due to irinotecan chemotherapy (the last dose of irinotecan is administered within 1 month);
• Patients who plan to receive 3 cycles of irinotecan chemotherapy (the dose of irinotecan ≥ 125mg/m2);
• Normal organ functions which can meet the requirements for systemic chemotherapy:

• Normal bone marrow function: absolute neutrophil count (ANC) ≥ 1.5×109/L, PLT ≥ 100×109/L, hemoglobin ≥ 90g/L;
• Normal renal functions: serum creatinine ≤ 1.5mg/dl (133μmol/L) and/or creatinine clearance ≥ 60ml/min;
• Normal hepatic functions: total serum bilirubin level ≤ 1.5 times of the upper limit of normal value (ULN), serum aspartate aminotransferase (AST) & alanine aminotransferase (ALT) ≤ 2.5× ULN; AST & ALT ≤ 5 × ULN if abnormal hepatic functions are caused by a potentially malignant tumor.
• Patients who can understand and complete the questionnaires in the case report form;
• Patients who can understand and sign the informed consent form, is well compliant, and can be followed up.

Exclusion criteria

• Patients with diagnosed depression, obsession or/and schizophrenia;
• Patients with diagnosed inflammatory bowel diseases (including Crohn's disease, ulcerative colitis)
• Patient with active tuberculosis and other uncontrolled infections;
• Patient who has previously received radiotherapy on the abdominal cavity or pelvic cavity;
• Pregnant or lactating women;
• Patient who previously had or is now having thromboembolic events.