Curcumin and Gemcitabine in Patients with Advanced Pancreatic Cancer
Nutr Cancer. 2010; 62(8):1137-41.
As discussed earlier, pancreatic cancer is an aggressive disease with an extremely poor prognosis. Gemcitabine is the standard chemotherapy for pancreatic cancer due to its improved clinical benefit response (CBR) and overall survival advantage over fluorouracil (5-FU). Its manageable toxicity profile makes it an attractive agent to investigate in combination with newer agent. Earlier studies showed thatCurcumin has antiproliferative effect and increases cytotoxic effect of gemcitabine in combination on pancreatic adenocarcinoma cell lines which may be due to down regulation of COX-2 and p-ERK1/2 levels. Recent tumor studies on mice showed that Curcumin could sensitize pancreatic cancer to gemcitabine in vitro and in vivo.
To evaluate the activity and feasibility of gemcitabine in combination with Curcumin in patients with advanced pancreatic cancer.
An open-labeled Phase II trial of gemcitabine concurrent with Curcumin was planned. Seventeen patients with qualifying eligibility criteria were enrolled for the study. They were administered 8,000 mg of Curcumin daily orally in combination with gemcitabine 1,000 mg/m2 intravenously weekly for 3 of 4 week. The Curcumin was divided into 2 daily doses 4,000 mg each, empty stomach. The gemcitabine dose was adjusted according to complete blood count prior to each administration based on medical decision. The Curcumin dose was reduced by 50% for Grade 2 toxicity and was suspended for Grade 3 toxicity.
- 5 patients discontinued the Curcumin component of the combined treatment due to abdominal discomfort.
- Gastrointestinal toxicity appeared in 7 patients (including 5 above patients) with a feeling of abdominal fullness and pain and dose of Curcumin was reduced to 50 %.
- Eleven patients were eligible for evaluation of gemcitabine and Curcumin combination. One patient (9%) had partial response for 7 months, 4 (36%) had stable disease for 2, 3, 6, and 12 months, and 6 (55%) had tumor progression with time of tumor progression (TTP) 1-12 months (median 2½) and overall survival 1-24 months (median 5).
In the clinical on advanced cancer patients only 11 patients out of 17 initially recruited were evaluable at the end of the trial. Duration of response or stable disease ranged from 2 months to 12 months, however owing to small sample size and early termination of study did not allow a real efficacy evaluation. To increase the level of exposure the authors of this study suggested use of adjuvants like Piperine to increase the bioavailability of the Curcumin to reach the efficacious levels of Curcumin.
This study was later followed by another clinical study which found that efficacious dosage of Curcumin at 8000 mg can be obtained with 100% compliance in pancreatic cancer patients