Faculty Collaboration Database

Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 2008 Jul 15;14(14):4491-9

Date

07/17/2008

Pubmed ID

18628464

DOI

10.1158/1078-0432.CCR-08-0024

Scopus ID

2-s2.0-51649118928 (requires institutional sign-in at Scopus site)   1168 Citations

Abstract

PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer.

EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored.

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.

Author List

Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, Ng CS, Badmaev V, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adult
Aged
Antineoplastic Agents
Curcumin
Cyclooxygenase 2
Cytokines
Electrophoretic Mobility Shift Assay
Female
Humans
Immunohistochemistry
Male
Middle Aged
NF-kappa B
Pancreatic Neoplasms