Document Detail


Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions.
MedLine Citation:
PMID:  11712783     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Curcumin (diferuloylmethane), a yellow substance from the root of the plant Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine skin, stomach, intestine and liver. However, the toxicology, pharmacokinetics and biologically effective dose of curcumin in humans have not been reported. This prospective phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions: 1) recently resected urinary bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography (HPLC). A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87 microM, respectively. Urinary excretion of curcumin was undetectable. One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment. In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of intestinal metaplasia of the stomach, I out of 4 patients with CIN and 2 out of 6 patients with Bowen's disease. In conclusion, this study demonstrated that curcumin is not toxic to humans up to 8,000 mg/day when taken by mouth for 3 months. Our results also suggest a biologic effect of curcumin in the chemoprevention of cancer.
Authors:
A L Cheng; C H Hsu; J K Lin; M M Hsu; Y F Ho; T S Shen; J Y Ko; J T Lin; B R Lin; W Ming-Shiang; H S Yu; S H Jee; G S Chen; T M Chen; C A Chen; M K Lai; Y S Pu; M H Pan; Y J Wang; C C Tsai; C Y Hsieh
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Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase I; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  21     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2001 Jul-Aug
Date Detail:
Created Date:  2001-11-19     Completed Date:  2001-12-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2895-900     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei. andrew@ha.mc.ntu.edu.tw
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Anticarcinogenic Agents / administration & dosage,  adverse effects,  pharmacokinetics,  therapeutic use*
Arsenicals / adverse effects
Bowen's Disease / chemically induced,  drug therapy*
Carcinoma, Transitional Cell / drug therapy*
Cervical Intraepithelial Neoplasia / drug therapy*
Curcumin / administration & dosage,  adverse effects,  pharmacokinetics,  therapeutic use*
Dose-Response Relationship, Drug
Female
Humans
Leukoplakia, Oral / drug therapy*
Male
Metaplasia
Middle Aged
Neoplasm Recurrence, Local / prevention & control
Precancerous Conditions / drug therapy*
Prospective Studies
Risk
Skin Neoplasms / chemically induced,  drug therapy*
Stomach / pathology*
Stomach Neoplasms / prevention & control*
Treatment Outcome
Urinary Bladder Neoplasms / drug therapy*
Uterine Cervical Neoplasms / drug therapy*
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Arsenicals; 458-37-7/Curcumin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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