A phase I/II study of gemcitabine-based chemotherapy plus Curcumin for patients with gemcitabine-resistant pancreatic cancer.
Cancer Chemother Pharmacol. 2011; 68(1):157-64.
As discussed earlier Gemcitabine is given as a standard therapy for advanced pancreatic cancer, however the patient survival rate is dismal and clinical condition who failed gemcitabine based chemotherapy was generally poor. Prior to this clinical study, the synergistic effects of Curcumin on Gemcitabine in preclinical studies have been reported, which prompts for further detailed study to determine the safety and feasibility of oral Curcumin in combination with Gemcitabine based chemotherapy in pancreatic cancer patients.
To conduct Phase I/II study for determining the safety and feasibility of oral Curcumin in combination with gemcitabine-based chemotherapy in patients with pancreatic cancer.
Twenty one patients were enrolled for phase I and phase II clinical studies that showed disease progression during gemcitabine-based chemotherapy and met other eligibility criteria. Nineteen patients (90 %) received gemcitabine/S-1 combination therapy and 2 patients (10%) received gemcitabine monotherapy. In combination therapy patients were administered Curcumin at a daily dosage of 8 g/day along with intravenous administration of gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 and 60 mg/m2 of S-1 orally for 14 consecutive days every 3 weeks. After initiation of Curcumin intake dose and schedule of gemcitabine –based chemotherapy was adjusted to discretion of individual physicians.
The primary endpoint was safety for the phase I study and treatment completion rate (TCR) of oral Curcumin daily for phase II study. There was no difference in Curcumin dose between the phase I and phase II study. The secondary endpoint for phase II study were response rate, overall survival (OS) and compliance rate of Curcumin.
- In the phase I study no dose limiting toxicity (DLT) was observed at 8 g/day, so this dose was recommended for the following phase II study.
- In spite of high amount for intake all the 19 patients were able to take more than 90% of Curcumin scheduled in this clinical trial yielding median compliance rate of oral Curcumin 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%).
- Out of 5 patients tested for plasma Curcumin level, except one (412 ng/ml; case 5), values ranged from 29 to 91 ng/ml.
The toxicity profile of this study was comparable to that observed in patients treated with Gemcitabine/S-1 combination therapy, thus adding oral Curcumin to the Gemcitabine treatment did not increase any toxicity in patients and also supported long term use. There was 100% compliance despite the poor condition of the patients after suffering failure of Gemcitabine based chemotherapy. Combination therapy using 8 g of Curcumin daily with Gemcitabine based chemotherapy was found to meet the both the phase I and phase II end points of the clinical trial and warrants further investigation into its efficacy.