xcht for irinotecan-induced gut toxicities (randomized controlled trial)

Conditions: Xiao Chai Hu Tang; Irinotecan-induced Diarrhea

Summary: randomized double-blind placebo-controlled trial (rct) study, to determine the impact of xcht on irinotecan-induced severe delayed-onset diarrhea (sdod), and to determine the feasibility of using plasma raloxifene-4'-glucuronide as a probe for intestinal ugt activity.

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.

Eligibility criteria:
inclusion criteria: 1. malignant tumor confirmed by histology or cytology; 2. age ≥ 18 years old, ≤ 75 years old; 3. ecog score of the patient ≤ 2 points; 4. patients who have diarrhea worse than grade 2 due to irinotecan chemotherapy (the last dose of irinotecan is administered within 1 month); 5. patients who plan to receive 3 cycles of irinotecan chemotherapy (the dose of irinotecan ≥ 125mg/m2); 6. 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. 7. patients who can understand and complete the questionnaires in the case report form; 8. patients who can understand and sign the informed consent form, is well compliant, and can be followed up. exclusion criteria: 1. patients with diagnosed depression, obsession or/and schizophrenia; 2. patients with diagnosed inflammatory bowel diseases (including crohn's disease, ulcerative colitis) 3. patient with active tuberculosis and other uncontrolled infections; 4. patient who has previously received radiotherapy on the abdominal cavity or pelvic cavity; 5. pregnant or lactating women; 6. patient who previously had or is now having thromboembolic events.

Keywords: malignant tumor irinotecan-induced diarrhea xiao chai hu tang classical chinese formula pharmacokinetic mechanism