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.
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We thank Kazuyuki Miura and Megumi Horikawa for their contributions to data management and Yasuko Nakagawa for her contribution to sample collection and preparation. This work was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (24590655) and the Japanese Research Foundation for Clinical Pharmacology.
Conflicts of interest
A. Imaizumi is a consultant to Theravalues Corporation, and Y. Otsuka is an employee of Theravalues Corporation.
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Kanai, M., Otsuka, Y., Otsuka, K. et al. A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin®) in cancer patients. Cancer Chemother Pharmacol 71, 1521–1530 (2013). https://doi.org/10.1007/s00280-013-2151-8
- Pancreatic cancer