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A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin®) in cancer patients

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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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Acknowledgments

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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Authors and Affiliations

  1. Outpatient Oncology Unit, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Masashi Kanai, Takafumi Nishimura, Yukiko Mori, Shigemi Matsumoto & Tsutomu Chiba

  2. Theravalues Corporation, Tokyo, Japan

    Yoshihiko Otsuka & Atsushi Imaizumi

  3. Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan

    Kazunori Otsuka & Hiroyuki Shibata

  4. Department of Medical Management and Informatics, Hokkaido Information University, Hokkaido, Japan

    Maremi Sato & Jun Nishihira

  5. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Michiya Kawaguchi & Etsuro Hatano

  6. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yuzo Kodama & Tsutomu Chiba

  7. Department of Hepatology, Osaka City University Hospital, Osaka, Japan

    Yoshiki Murakami

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  1. Masashi Kanai
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  2. Yoshihiko Otsuka
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Correspondence to Masashi Kanai.

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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

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  • DOI: https://doi.org/10.1007/s00280-013-2151-8

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