Schindler E, Amantea M A, Karlsson M O, Friberg L E
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Pfizer Inc., La Jolla, California, USA.
CPT Pharmacometrics Syst Pharmacol. 2016 Apr;5(4):173-81. doi: 10.1002/psp4.12057. Epub 2016 Mar 16.
Pharmacometric models were developed to characterize the relationships between lesion-level tumor metabolic activity, as assessed by the maximum standardized uptake value (SUVmax) obtained on [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), tumor size, and overall survival (OS) in 66 patients with gastrointestinal stromal tumor (GIST) treated with intermittent sunitinib. An indirect response model in which sunitinib stimulates tumor loss best described the typically rapid decrease in SUVmax during on-treatment periods and the recovery during off-treatment periods. Substantial interindividual and interlesion variability were identified in SUVmax baseline and drug sensitivity. A parametric time-to-event model identified the relative change in SUVmax at one week for the lesion with the most pronounced response as a better predictor of OS than tumor size. Based on the proposed modeling framework, early changes in FDG-PET response may serve as predictor for long-term outcome in sunitinib-treated GIST.
建立了药代动力学模型，以表征66例接受间歇性舒尼替尼治疗的胃肠道间质瘤（GIST）患者中，通过[（18）F] - 氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）获得的最大标准化摄取值（SUVmax）评估的病灶水平肿瘤代谢活性、肿瘤大小与总生存期（OS）之间的关系。一种间接反应模型，其中舒尼替尼刺激肿瘤缩小，最能描述治疗期间SUVmax通常快速下降以及停药期间的恢复情况。在SUVmax基线和药物敏感性方面发现了显著的个体间和病灶间变异性。一个参数化的事件时间模型确定，对于反应最明显的病灶，一周时SUVmax的相对变化比肿瘤大小更能预测OS。基于所提出的建模框架，FDG - PET反应的早期变化可能作为舒尼替尼治疗GIST长期预后的预测指标。
