Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.
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Authors | Navneet Dhillon, Bharat B Aggarwal, Robert A Newman, Robert A Wolff, Ajaikumar B Kunnumakkara, James L Abbruzzese, Chaan S Ng, Vladimir Badmaev, Razelle Kurzrock |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 14
Issue 14
Pg. 4491-9
(Jul 15 2008)
ISSN: 1078-0432 [Print] United States |
PMID | 18628464
(Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Cytokines
- NF-kappa B
- Cyclooxygenase 2
- Curcumin
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Topics |
- Adenocarcinoma
(drug therapy)
- Adult
- Aged
- Antineoplastic Agents
(metabolism, therapeutic use)
- Curcumin
(metabolism, therapeutic use)
- Cyclooxygenase 2
(drug effects, metabolism)
- Cytokines
(blood, drug effects)
- Electrophoretic Mobility Shift Assay
- Female
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- NF-kappa B
(drug effects, metabolism)
- Pancreatic Neoplasms
(drug therapy)
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