PMID- 11712783
OWN - NLM
STAT- MEDLINE
DCOM- 20011210
LR  - 20230120
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 21
IP  - 4B
DP  - 2001 Jul-Aug
TI  - Phase I clinical trial of curcumin, a chemopreventive agent, in patients with 
      high-risk or pre-malignant lesions.
PG  - 2895-900
AB  - 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.
FAU - Cheng, A L
AU  - Cheng AL
AD  - Department of Internal Medicine, National Taiwan University College of Medicine, 
      Taipei. andrew@ha.mc.ntu.edu.tw
FAU - Hsu, C H
AU  - Hsu CH
FAU - Lin, J K
AU  - Lin JK
FAU - Hsu, M M
AU  - Hsu MM
FAU - Ho, Y F
AU  - Ho YF
FAU - Shen, T S
AU  - Shen TS
FAU - Ko, J Y
AU  - Ko JY
FAU - Lin, J T
AU  - Lin JT
FAU - Lin, B R
AU  - Lin BR
FAU - Ming-Shiang, W
AU  - Ming-Shiang W
FAU - Yu, H S
AU  - Yu HS
FAU - Jee, S H
AU  - Jee SH
FAU - Chen, G S
AU  - Chen GS
FAU - Chen, T M
AU  - Chen TM
FAU - Chen, C A
AU  - Chen CA
FAU - Lai, M K
AU  - Lai MK
FAU - Pu, Y S
AU  - Pu YS
FAU - Pan, M H
AU  - Pan MH
FAU - Wang, Y J
AU  - Wang YJ
FAU - Tsai, C C
AU  - Tsai CC
FAU - Hsieh, C Y
AU  - Hsieh CY
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Arsenicals)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anticarcinogenic Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Arsenicals/adverse effects
MH  - Bowen's Disease/chemically induced/*drug therapy
MH  - Carcinoma, Transitional Cell/*drug therapy
MH  - Curcumin/administration & dosage/adverse effects/pharmacokinetics/*therapeutic 
      use
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Leukoplakia, Oral/*drug therapy
MH  - Male
MH  - Metaplasia
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/prevention & control
MH  - Precancerous Conditions/*drug therapy
MH  - Prospective Studies
MH  - Risk
MH  - Skin Neoplasms/chemically induced/*drug therapy
MH  - Stomach/*pathology
MH  - Stomach Neoplasms/*prevention & control
MH  - Treatment Outcome
MH  - Urinary Bladder Neoplasms/*drug therapy
MH  - Uterine Cervical Neoplasms/*drug therapy
MH  - Uterine Cervical Dysplasia/*drug therapy
EDAT- 2001/11/20 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/20 10:00
PHST- 2001/11/20 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/20 10:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2001 Jul-Aug;21(4B):2895-900.