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Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 6, pp 1521–1530 | Cite as

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

  • Masashi KanaiEmail author
  • Yoshihiko Otsuka
  • Kazunori Otsuka
  • Maremi Sato
  • Takafumi Nishimura
  • Yukiko Mori
  • Michiya Kawaguchi
  • Etsuro Hatano
  • Yuzo Kodama
  • Shigemi Matsumoto
  • Yoshiki Murakami
  • Atsushi Imaizumi
  • Tsutomu Chiba
  • Jun Nishihira
  • Hiroyuki Shibata
Original Article

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.

Keywords

Curcumin Bioavailability Theracurmin® Gemcitabine Pancreatic cancer 

Notes

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Masashi Kanai
    • 1
    Email author
  • Yoshihiko Otsuka
    • 2
  • Kazunori Otsuka
    • 3
  • Maremi Sato
    • 4
  • Takafumi Nishimura
    • 1
  • Yukiko Mori
    • 1
  • Michiya Kawaguchi
    • 5
  • Etsuro Hatano
    • 5
  • Yuzo Kodama
    • 6
  • Shigemi Matsumoto
    • 1
  • Yoshiki Murakami
    • 7
  • Atsushi Imaizumi
    • 2
  • Tsutomu Chiba
    • 1
    • 6
  • Jun Nishihira
    • 4
  • Hiroyuki Shibata
    • 3
  1. 1.Outpatient Oncology UnitKyoto University HospitalKyotoJapan
  2. 2.Theravalues CorporationTokyoJapan
  3. 3.Department of Clinical OncologyAkita University Graduate School of MedicineAkitaJapan
  4. 4.Department of Medical Management and InformaticsHokkaido Information UniversityHokkaidoJapan
  5. 5.Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
  6. 6.Department of Gastroenterology and Hepatology, Graduate School of MedicineKyoto UniversityKyotoJapan
  7. 7.Department of HepatologyOsaka City University HospitalOsakaJapan

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