Prognostic factors of clinical responses in patients with advanced-stage intrahepatic cholangiocarcinoma followingAtractylodes lanceaadministration: A phase 2A clinical trial

Abstract

AbstractA statistical model is essential in determining the appropriate predictive indicators for therapies in many types of cancers. Predictors have been compared favorably to the traditional systems for many cancers. Thus, this study has been proposed as an alternative or a new standard approach. A recent study on the clinical efficacy ofAtractylodes lancea(Thunb) DC. (AL) revealed the higher clinical benefits in patients with advanced-stage intrahepatic cholangiocarcinoma (ICC) treated with AL compared with standard supportive care. we investigated the relationships between clinical efficacy and pharmacokinetic parameters of serum bioactivity of AL and its active constituent “atractylodin” and determined therapeutic ranges. Cox proportion hazard model and Receive Operating Characteristic (ROC) were applied to determine the cut-off values of AUC0-inf, Cmax, and Cavgassociated with therapeutic outcomes. Number-need to be treated (NNT) and relative risk (RR) was also applied to determine potential predictors. The AUC0-infof total AL bioactivity of> 96.71 µg*h/ml was identified as a promising predictor of disease prognosis,i.e., progression-free survival (PFS) and disease control rate (DCR). Cmaxof total AL bioactivity of>21.42 was identified as a predictor of the prognosis of death. The therapeutic range of total AL bioactivity for PFS and DCR is 14.48-65.8 µg/ml, and for overall survival is 10.97-65.8 µg/ml. The predictors of ICC disease prognosis were established based on the pharmacokinetics of total AL bioactivity. The information could be exploited to improve the clinical efficacy of AL in patients with advanced-stage ICC. These predictors will be validated in a phase 2B clinical study.