Journal Article

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

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

2013

Overview

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.

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: Aged / Aged, 80 and over / Antineoplastic agents / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - chemistry / Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics / Biliary Tract Neoplasms - drug therapy / Biliary Tract Neoplasms - metabolism / Biliary Tract Neoplasms - mortality / Biological and medical sciences / Biological Availability / Cancer Research / Curcumin - administration & dosage / Curcumin - adverse effects / Curcumin - chemistry / Curcumin - pharmacokinetics / Cytokines - antagonists & inhibitors / Cytokines - immunology / Disease-Free Survival / Dose-Response Relationship, Drug / Drug Administration Schedule / Drug Compounding / Drug Stability / Female / Gastroenterology. Liver. Pancreas. Abdomen / Humans / Liver. Biliary tract. Portal circulation. Exocrine pancreas / Male / Maximum Tolerated Dose / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / NF-kappa B - antagonists & inhibitors / Oncology / Original Article / Pancreatic Neoplasms - drug therapy / Pancreatic Neoplasms - metabolism / Pancreatic Neoplasms - mortality / Pharmacology. Drug treatments / Pharmacology/Toxicology / Quality of Life / Solubility / Tumors