PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: TCTR20210129007 (TCTR: www.clinicaltrials.in.th).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: TCTR20210129007 (TCTR: www.clinicaltrials.in.th).
摘要：
■统计模型对于确定许多类型癌症治疗的适当预测指标至关重要。对于许多癌症，预测因子已与传统系统进行了比较。因此，这项研究已被提出作为一种新的标准方法。苍术（Thunb）DC临床疗效的最新研究。（AL）显示，与标准支持治疗相比，接受AL治疗的晚期肝内胆管癌（ICC）患者的临床获益更高。我们研究了AL及其活性成分苍术苷的临床疗效与血清生物活性的药代动力学参数之间的关系，并确定了治疗范围。
■第1组晚期ICC患者接受每日剂量为1000mg的AL胶囊制剂（CMC-AL）的标准化提取物90天。第2组接受每日1000mgCMC-AL的剂量，持续14天，随后是1500毫克，持续14天，和2000毫克，持续62天。第3组（对照组）接受姑息治疗。Cox比例风险模型和接收器工作特性（ROC）用于确定AUC0-inf的截止值，Cmax,和Cavg与治疗结果相关。需要治疗的数量（NNT）和相对风险（RR）也被用来确定潜在的预测因素。
■总AL生物活性的AUC0-inf>96.71µg小时/毫升被确定为疾病预后的有希望的预测指标，也就是说,无进展生存期（PFS）和疾病控制率（DCR）。总AL生物活性的Cmax>21.42被确定为生存预后的预测因子。PFS和DCR的总AL生物活性的治疗范围为14.48至65.8µg/ml，总生存率为10.97至65.8µg/ml。结论：基于总AL生物活性的药代动力学建立了ICC疾病预后的预测因子。这些信息可用于提高晚期ICC患者AL的临床疗效。这些预测因子将在2B期临床研究中得到验证。
■TCTR20210129007（TCTR：www.临床试验。。th).
■第1组晚期ICC患者接受每日剂量为1000mg的AL胶囊制剂（CMC-AL）的标准化提取物90天。第2组接受每日1000mgCMC-AL的剂量，持续14天，随后是1500毫克，持续14天，和2000毫克，持续62天。第3组（对照组）接受姑息治疗。Cox比例风险模型和接收器工作特性（ROC）用于确定AUC0-inf的截止值，Cmax,和Cavg与治疗结果相关。需要治疗的数量（NNT）和相对风险（RR）也被用来确定潜在的预测因素。
■总AL生物活性的AUC0-inf>96.71µg小时/毫升被确定为疾病预后的有希望的预测指标，也就是说,无进展生存期（PFS）和疾病控制率（DCR）。总AL生物活性的Cmax>21.42被确定为生存预后的预测因子。PFS和DCR的总AL生物活性的治疗范围为14.48至65.8µg/ml，总生存率为10.97至65.8µg/ml。结论：基于总AL生物活性的药代动力学建立了ICC疾病预后的预测因子。这些信息可用于提高晚期ICC患者AL的临床疗效。这些预测因子将在2B期临床研究中得到验证。
■TCTR20210129007（TCTR：www.临床试验。。th).
