Phase II Trial of Curcumin in Patients with Advanced Pancreatic Cancer
Clin Cancer Res. 2008; 14(14):4491-9.
Pancreatic adenocarcinoma is one of the most lethal cancers with very poor survival rate which is measured in weeks only. The current available treatment available for Pancreatic cancer patients include administration of gemcitabine and erlotinib, both of which produce objective response in <10 % of patients. With inflammation at the center stage for the development of various chronic life style diseases and chronic inflammation itself playing key role in development of cancerous tissue, role of inflammatory mediators has been well studied in various types of cancers. Studies have indicated that inflammatory transcription factor nuclear factor-kB (NF-kB) is constitutively active in patients suffering from pancreatic cancer. NF-kB is well known for its role in suppression of apoptosis, tumor growth, invasion, angiogenesis and metastatis of cancer. As Curcumin has been shown to inhibit NF-кB activation, it has been studied as an agent which can target NF-kB in pancreatic cancer patients.
Previously conducted Phase I studies of Curcumin have shown that it can be safely administered up to 8g/day.
To conduct a Phase II study, to determine the biological activity of oral Curcumin in patients with pancreatic cancer.
In nonrandomized, open-label, phase II trial of Curcumin, 25 patients were administered Curcumin orally at a dose of 8 g/day for 8 weeks. A complete history, physical examination, blood test, electrocardiogram, chest radiograph and diagnostic imaging were done at baseline and at the end of the study. Except diagnostic imaging all procedures were repeated at ~4 weeks of the study. Safety evaluation and tumor response was also assessed during the study.
Serum cytokine level for interleukin (IL)-6, IL-8, IL-10 and IL-1 receptor antagonists (IL-1RA) were measured in both diseased and controlled samples. The effect of orally administered Curcumin on constitutive and tumor necrosis factor-α-induced binding expression of NF-кB, cyclooxygenase-2 (COX-2), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) in peripheral blood mononuclear cells (PBMC) and pharmacokinetics of Curcumin was also monitored during the study.
The parameters evaluated during the trial (i.e. at baseline and at the end of the study) included fasting glucose level and lipid profile (total cholesterol, LDL-C, HDL-C and Triglycerides) along with liver and kidney function tests.
- No treatment related toxic effects were observed. Two patients showed clinical biological activity. One patient had ongoing stable disease for >18 months (Patient 14). Interestingly, one additional patient had a brief, but marked tumor regression (73%) [Patient 8].
- On treatment of patients with Curcumin, immunocytochemistry showed a decline in NF-кB compared with that in normal volunteers.
- Expression of COX-2, activated pSTAT3 in PBMCs declined in treatment with Curcumin.
Oral Curcumin is well tolerated and, despite its limited absorption, has biological activity insome patients with pancreatic cancer.