Study: The Use of Curcumin With Gemcitabine in Patients With Advanced Pancreatic Cancer

reference

Kanai M, Yoshimura K, Asada M, et al. A Phase I/II Study of Gemcitabine-Based Chemotherapy Plus Curcumin in Patients With Gemcitabine-Resistant Pancreatic Cancer.Cancer Chemother Pharmacol. September 22, 2010. [Epub ahead of print]

design

Phase I/II safety and feasibility study of oral curcumin

Endpoints

The primary endpoint of the Phase I study was the safety of 8 grams of oral curcumin. The primary endpoint of the phase II study was the completion rate of oral curcumin treatment. Secondary endpoints for phase II were response rate, overall survival (OS) and compliance.

Participant

21 patients with advanced pancreatic cancer whose disease progressed on single-agent gemcitabine chemotherapy.

Key findings

No dose-limiting toxicities were observed in the phase I study of 8.0 grams of curcumin daily in 3 patients. None of the 21 study participants discontinued the study due to intolerance to curcumin. Plasma curcumin was tested in 5 patients and ranged from 29 to 91 ng/ml, except for one patient with a value of 412 ng/ml. Compliance was very good: 19 (90%) participants were able to consume more than 90% of the prescribed daily dose. Seventeen (81%) participants died during the study period and three were still alive at the time of publication. Median overall survival (OS) was 161 days (95% CI: 109-223 days). The one-year survival rate was 19%.

Effects on practice

The anti-cancer effects of curcumin in high doses are well documented. Its anticancer effects are largely due to its ability to reduce the activation of NF-kB, leading to its antiproliferative, antiangiogenic, antiinvasive and proapoptotic effects on cancer cells. In addition, there are in vitro demonstrations of its action as a synergistic agent with several chemotherapies, including 5-fluorouracil, vinorelbine and gemcitabine.^1.2Given the potential of curcumin as both an anticancer agent and a chemotherapy sensitizer, there is great interest in finding the appropriate applications and dosages for its use in integrative oncology.

This small study showed that high doses of curcumin are well tolerated by patients with advanced pancreatic cancer, despite possible digestive impairments.

This small study showed that high doses of curcumin are well tolerated by patients with advanced pancreatic cancer, despite possible digestive impairments. Although it is believed that consuming curcumin along with fat would optimize absorption, this is not disclosed anywhere in the publication. Patients were given the opportunity to divide the dose throughout the day to increase tolerability, which the authors believe may have resulted in better tolerability than in previous studies.

While this study demonstrated safety and tolerability, what about patient outcomes? There are good reasons to speculate that the combination of curcumin and gemcitabine had a synergistic cytotoxic effect. Kunnamakkara et al. showed in vitro and in a mouse model of pancreatic cancer that the combination of curcumin with gemcitabine resulted in lower tumor volume after treatment than gemcitabine alone.³A recent study confirmed this and showed that curcumin and gemcitabine worked synergistically in tumor reduction of bladder cancer.⁴

The median survival time for patients whose disease has progressed on gemcitabine and who are receiving supportive care only is approximately 10 weeks.⁵In this study, the median survival time was 23 weeks. However, it should be noted that the secondary endpoints of response rate and overall survival may have been influenced by the comedication S-1. Of the 21 participants included in the study, 19 received S-1, an oral fluoropyrimidine that has shown possible benefit in patients with advanced pancreatic cancer.^6.7This certainly contradicts the conclusions we can draw from the use of curcumin and gemcitabine.

The use of curcumin with gemcitabine in patients with advanced pancreatic cancer requires further research as both in vitro and in vivo data suggest synergistic cytotoxic effects. Until more definitive research is published, we should definitely consider using curcumin in patients taking gemcitabine, as there is no evidence that it interferes with treatment. However, keep in mind that the dose should be high to reproduce the research.

For more research on integrative oncology, click here Here.