Outpatient Oncology Unit, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Cancer Chemother Pharmacol. 2013 Jun;71(6):1521-30. doi: 10.1007/s00280-013-2151-8. Epub 2013 Mar 30.
A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients.
Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated.
Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin administration for >9 months.
Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.
越来越多的临床前研究表明姜黄素可能是一种很有前途的抗癌药物；然而，其生物利用度差一直是其临床应用的主要障碍。为了克服这个问题，我们开发了一种新形式的姜黄素（Theracurmin），并报告称在健康志愿者中单次给予Theracurmin 后可以安全地达到高血浆姜黄素水平。在这项研究中，我们旨在评估癌症患者重复给予 Theracurmin 的安全性。
接受标准化疗失败的胰腺或胆道癌患者有资格参加这项研究。基于我们之前的药代动力学研究，我们选择含有 200 毫克姜黄素的 Theracurmin（级别 1）作为起始剂量，并且剂量安全地增加到含有 400 毫克姜黄素的级别 2。Theracurmin 每天与标准吉西他滨为基础的化疗一起口服给药。除了安全性和药代动力学数据外，还评估了 NF-κB 活性、细胞因子水平、疗效和生活质量评分。
10 名患者被分配到 1 级，6 名患者被分配到 2 级。Theracurmin 给药后姜黄素的峰值血浆浓度（中位数）在 1 级为 324ng/ml（范围，47-1029ng/ml），在 2 级为 440ng/ml（范围，179-1380ng/ml）。未观察到意外的不良事件，有 3 名患者安全地继续接受 Theracurmin 治疗超过 9 个月。
在接受吉西他滨为基础的化疗的癌症患者中，Theracurmin 实现的高浓度姜黄素的重复全身暴露并未增加不良事件的发生率。
