A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin?) in cancer patients
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- 作者：Masashi Kanai (1)
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) - 关键词：Curcumin ; Bioavailability ; Theracurmin? ; Gemcitabine ; Pancreatic cancer
- 刊名：Cancer Chemotherapy and Pharmacology
- 出版年：2013
- 出版时间：June 2013
- 年：2013
- 卷：71
- 期：6
- 页码：1521-1530
- 全文大小：256KB
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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. Outpatient Oncology Unit, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
2. Theravalues Corporation, Tokyo, Japan
3. Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan
4. Department of Medical Management and Informatics, Hokkaido Information University, Hokkaido, Japan
5. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
6. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
7. Department of Hepatology, Osaka City University Hospital, Osaka, Japan - ISSN：1432-0843
文摘
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-,029?ng/mL) at Level 1 and 440?ng/mL (range, 179-,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.