Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 6, pp 1521–1530

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

Authors

    • Outpatient Oncology UnitKyoto University Hospital
  • Yoshihiko Otsuka
    • Theravalues Corporation
  • Kazunori Otsuka
    • Department of Clinical OncologyAkita University Graduate School of Medicine
  • Maremi Sato
    • Department of Medical Management and InformaticsHokkaido Information University
  • Takafumi Nishimura
    • Outpatient Oncology UnitKyoto University Hospital
  • Yukiko Mori
    • Outpatient Oncology UnitKyoto University Hospital
  • Michiya Kawaguchi
    • Department of Surgery, Graduate School of MedicineKyoto University
  • Etsuro Hatano
    • Department of Surgery, Graduate School of MedicineKyoto University
  • Yuzo Kodama
    • Department of Gastroenterology and Hepatology, Graduate School of MedicineKyoto University
  • Shigemi Matsumoto
    • Outpatient Oncology UnitKyoto University Hospital
  • Yoshiki Murakami
    • Department of HepatologyOsaka City University Hospital
  • Atsushi Imaizumi
    • Theravalues Corporation
  • Tsutomu Chiba
    • Outpatient Oncology UnitKyoto University Hospital
    • Department of Gastroenterology and Hepatology, Graduate School of MedicineKyoto University
  • Jun Nishihira
    • Department of Medical Management and InformaticsHokkaido Information University
  • Hiroyuki Shibata
    • Department of Clinical OncologyAkita University Graduate School of Medicine
Original Article

DOI: 10.1007/s00280-013-2151-8

Cite this article as:
Kanai, M., Otsuka, Y., Otsuka, K. et al. Cancer Chemother Pharmacol (2013) 71: 1521. doi:10.1007/s00280-013-2151-8

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

CurcuminBioavailabilityTheracurmin®GemcitabinePancreatic cancer

Copyright information

© Springer-Verlag Berlin Heidelberg 2013