Irinotecan is a commonly used salvage chemotherapy drug for children with relapsed and refractory solid tumors. Common dose-limiting toxicities of irinotecan include abdominal pain and diarrhea. Studies have shown that patients with UGT1A16 gene mutations have a higher incidence of these side effects, thereby limiting the dosage of irinotecan. The combination of irinotecan with temozolomide and vincristine is a common salvage chemotherapy regimen for children with relapsed and refractory solid tumors. Currently, the recommended dose of irinotecan is 50mg/m², but there is still significant room for improvement in the efficacy of VIT for these children. Whether patients with wild-type UGT1A16 can further increase the dosage of irinotecan, thereby enhancing the efficacy of the VIT regimen, is the focus of our research.
Age < 18 years.
Relapsed and refractory childhood solid tumors (pathologically confirmed). Definition of relapsed and refractory patients: 1. Patients who fail to achieve GPR or CR after first-line treatment are defined as refractory; 2. Patients who achieve CR after first-line treatment but relapse after more than 1 month are defined as relapsed.
Must have undergone UGT1A1*6 genotype testing (provided free of charge by Jiangsu Hengrui Medicine Co., Ltd.), with results being wild type (T/T).
Patients must be at least 3 weeks post the last myelosuppressive chemotherapy and at least 6 months post hematopoietic stem cell transplantation, 2 weeks post local radiotherapy, 6 months post craniospinal or extensive pelvic radiotherapy, or 6 weeks post extensive bone marrow radiotherapy.
Patients who have previously received chemotherapy with irinotecan combined with temozolomide and vincristine, or patients who have progressed after receiving treatment with irinotecan or temozolomide;
Patients receiving P450 enzyme-inducing antiepileptic drugs (antiepileptic drugs affect the clearance of irinotecan);
During the study period, patients must not receive any other chemotherapy, radiotherapy, or granulocyte colony-stimulating therapy;
Patients positive for hepatitis B surface antigen;
Sequential
Irinotecan (CPT-11)
DrugIrinotecan will start at a dose of 50mg/m² and escalate to explore the maximum tolerated dose.
Temozolomide (TMZ)
DrugTMZ：100mg/m2/d，d1-5
Vincristine
DrugVCR: 1.5mg/m2/d(≯2mg), d1
MTD and DLT
The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan
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