title: A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients.
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.
authors.affiliation: Outpatient Oncology Unit, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. kanai@kuhp.kyoto-u.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanai
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Otsuka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Otsuka
authors.forename: Maremi
authors.initials: M
authors.lastname: Sato
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Mori
authors.forename: Michiya
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Etsuro
authors.initials: E
authors.lastname: Hatano
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Kodama
authors.forename: Shigemi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Imaizumi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shibata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D001682:Biological Availability; D003474:Curcumin / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D011788:Quality of Life; D012995:Solubility
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D003474:Curcumin