A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer

Outpatient Oncology Unit, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Cancer Chemotherapy and Pharmacology (Impact Factor: 2.77). 07/2011; 68(1):157-64. DOI: 10.1007/s00280-010-1470-2
Source: PubMed


Curcumin, a plant-derived natural polyphenol, could be a promising anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated the safety and feasibility of combination therapy using curcumin with gemcitabine-based chemotherapy.
Gemcitabine-resistant patients with pancreatic cancer received 8 g oral curcumin daily in combination with gemcitabine-based chemotherapy. The primary endpoint was safety for phase I and feasibility of oral curcumin for phase II study.
Twenty-one patients were enrolled. No dose-limiting toxicities were observed in the phase I study and oral curcumin 8 g/day was selected as the recommended dose for the phase II study. No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral curcumin was 100% (Range 79-100%). Median survival time after initiation of curcumin was 161 days (95% confidence interval 109-223 days) and 1-year survival rate was 19% (4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients tested.
Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy.

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    • "Henceforth combining them synergistically with synthetic chemotherapeutic drugs would yield a dependable therapeutic tool for circumventing cancer. Curcumin has augmented anticancer activity of gemcitabine and 5FU [26] [27] while resveratrol has sensitized human cancer cell lines such as neuroblastoma, glioblastoma , and breast carcinoma, prostate carcinoma to chemotherapeutic agents such as doxorubicin, cytarabine, taxol, and methotrexate [28]. Another flavonoid, myricetin in combination of with 5-fluorouracil was found to increase tumor chemosensitivity of esophageal cancer cells [29]. "
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