Pharmacokinetic Analysis of Prognostic Factors in Patients With Advanced-Stage Intrahepatic Cholangiocarcinoma Following the Administration of Capsule Formulation of the Standardized Extract of Atractylodes lancea (Thunb) DC.

BACKGROUND: A 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 a new standard approach. A recent study on the clinical efficacy of Atractylodes 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. METHODS: Group 1 of advanced-stage ICC patients received daily doses of 1000 mg of standardized extract of the capsule formulation of AL (CMC-AL) for 90 days. Group 2 received daily doses of 1000 mg of CMC-AL for 14 days, followed by 1500 mg for 14 days, and 2000 mg for 62 days. Group 3 (control group) received palliative care. Cox proportional hazard model and Receiver Operating Characteristic (ROC) were applied to determine the cut-off values of AUC0-inf, Cmax, and Cavg associated with therapeutic outcomes. Number needed to treat (NNT) and relative risk (RR) were also applied to determine potential predictors. RESULTS: The AUC0-inf of total AL bioactivity of >96.71 µg hour/ml was identified as a promising predictor of disease prognosis, that is, progression-free survival (PFS) and disease control rate (DCR). Cmax of total AL bioactivity of >21.42 was identified as a predictor of the prognosis of survival. The therapeutic range of total AL bioactivity for PFS and DCR is 14.48 to 65.8 µg/ml, and for overall survival is 10.97 to 65.8 µg/ml. Conclusions: 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. TRIAL REGISTRATION: TCTR20210129007 (TCTR: www.clinicaltrials.in.th).

The Impact of Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinoma: A Single Center Experience.

Objective: The present study aimed to study survival and complications of hepatocellular carcinoma (HCC) patients with Barcelona Clinic Liver Cancer (BCLC) stage C who received transarterial chemoembolization (TACE) at Rajavithi Hospital, Thailand. Material and Method: The method used was a descriptive retrospective study using data collected from patient medical records from 2008 to 2012. The general information, complications, and causes of death of the patients were presented with descriptive statistics. Survival was analyzed using the Kaplan-Meier method. Results: During the 5-year period, our institution performed TACE on 396 patients. While 57 cases were classified as BCLC stage C, only 44 cases had complete records. The mean age of the patients was 56.3 years with an age range from 30 to 75 years. Thirty-six cases or 81.8% were male. Twenty-six cases or 59.1% had hepatitis B infections. Thirty-five cases or 79.5% were Child-Pugh A. The median survival time was 7.1 months. The most common complication was post-embolization syndrome which occurred in 39 patients (88.6%). Liver failure was a major procedural-related complication which occurred in 8 patients (18.2%) and was responsible for three deaths (6.8%). Conclusion: TACE in HCC patients with BCLC stage C at Rajavithi Hospital was an effective and safe palliative treatment.