Objective:Population pharmacokinetics analysis explored the pharmacokinetics of anlotinib in children with soft tissue sarcomas (STS) and identified the optimal dose for children across various age brackets. Method:From 2021 to 2023, a single dose of anlotinib (4.62 mg/m2) was orally administered in 16 children with advanced STS in 8 days. Anlotinib plasma concentration was evaluated by LC-MS/MS. Pharmacokinetic models were developed using nonlinear mixed-effects modelling. The effect of predefined covariates on pharmacokinetic parameters was assessed. Results:Totally 128 samples from 16 children (aged 5-14) were collected for pop-PK analysis. The two-compartment model was most consistent with the data of oral anlotinib in pediatrics with advanced STS, and the relevant parameters were: Ka (h-1) 0.419; Vc/F (L) 760; Q (L∙h-1) 21.2; Vp/F (L) 547. Covariate screening showed that the clearance of anlotinib gradually increased with age in a sigmoidal relationship, the maximum CL/F was 15.7L∙h-1, and age of median clearance (Age50) was 6.84 years; the Vc/F increased linearly with BSA. Dose of 8 mg anlotinib for children aged 5-7, and 10 mg or 12 mg for children aged 8-10 would be expected to lead to a similar exposure of anlotinib compared with an adult patient receiving 12 mg. Conclusion:The population pharmacokinetics of orally administrated anlotinib were evaluated in pediatric advanced STS patients. BSA and age were significant physiologic factors on PK. A simulation of 8 mg anlotinib in children aged 5-7, 10 mg or 12 mg in 8-10 and 12 mg for children over 11 would get similar exposure of adults receiving 12mg.

Objectives: To summarize the clinical characteristics and outcome of infantile extracranial germ cell tumors(GCTs) from four different centers in China since the last 10 years. Methods: Fifteen cases of infantile extracranial GCTs diagnosed between January 1st, 2010 to December 31st, 2019 were evaluated. Results: Nine patients were males(60%) and six were females(40%). The median age was 5.2 months(ranges:2.4-11.8months). There were six cases(40%) in retroperitoneum, six cases(40%) in sacrococcygeal, one case(6.6%) in testicular, one case(6.6%) in hip and one case(6.6%) in mediastinum. Histologically, there were 10 cases(66.6%) of immature teratoma, 3(20%) mixed GCTs and 2(13.3%) malignant GCTs. One case was stageII(6.6%), eleven stageIII(73.3%), one stageIV(6.6%) and two cases were unclear(13.3%). Nine cases(60%) had alpha-fetoprotein(AFP) level of higher than 1000ng/ml. All of the cases received adjuvant chemotherapy in which platinum-based chemotherapy regimens were mostly used. The median follow-up time was 31 months(range: 3–81 months). At the end of treatment, 12 patients got CR(80%), 1 PR(6.7%) and 2 NR(13.3%). During the follow-up period, 12 patients alive without disease and 3 patient who did not got CR at the end of treatment died of disease progression. Conclusions: Most of infantile extracranial GCTs located outside the gonads. Sacrococcygeal and retroperitoneal regions were common sites. Histologically, teratoma was more common in infantile GCTs. Early diagnosis is needed and chemotherapy regimen needs to be further standardized in China. An evaluation system is needed to figure out treatment efficacy and prognosis in the future.