curcumin and Biliary-Tract-Neoplasms

Biliary cancer and pancreatic cancer are considered to be difficult diseases to cure. Although complete resection provides the only means of curing these cancers, the rate of resectability is not high. Therefore, chemotherapy is often selected in patients with advanced unresectable biliary-pancreatic cancer. Many combination chemotherapy regimens have been applied in clinical trials. However, the survival time is not satisfactory. On the other hand, most chemotherapeutic agents induce anti-apoptotic transcriptional factor nuclear factor kappa b (NF-κB) activation, and agent-induced NF-κB activation is deeply involved in the onset of chemoresistance. Recently, novel approaches to potentiating chemosensitivity in cases of biliary-pancreatic cancer using NF-κB inhibitors with cytotoxic agents have been reported, most of which comprise translational research, although some clinical trials have also been conducted. Nevertheless, to date, there is no breakthrough chemotherapy regimen for these diseases. As some reports show promising data, combination chemotherapy consisting of a NF-κB inhibitor with chemotherapeutic agents seems to improve chemosensitivity and prolong the survival time of biliary-pancreatic cancer patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Benzamidines; Biliary Tract Neoplasms; Bortezomib; Camptothecin; Curcumin; Deoxycytidine; Ditiocarb; Drug Resistance, Neoplasm; Gemcitabine; Guanidines; Humans; Irinotecan; Molecular Targeted Therapy; NF-kappa B; Paclitaxel; Pancreatic Neoplasms; Pregnenediones; Treatment Outcome

A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients.. Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated.. Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin administration for >9 months.. Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Biological Availability; Curcumin; Cytokines; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Compounding; Drug Stability; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; NF-kappa B; Pancreatic Neoplasms; Quality of Life; Solubility