Phase II study of curcumin and gemcitabine in patients with advanced pancreatic cancer

Abstract

15619 Background: The anti-metabolite gemcitabine is the standard chemotherapy for advanced pancreatic cancer.Yet, it produces an objective response in less than 10% of patients (pts), with a minor effect on survival. Curcumin, the active ingredient in the tumeric spice, has potent anti-proliferative activity, by interaction with several intracellular signal transduction pathways. Curcumin can also potentiates the antitumor effect of gemcitabine, as shown in pre-clinical models of pancreatic cancer. The presnt study was undertaken to evaluate the activity and feasibility of gemcitabine in combination with curcumin in pts with advanced pancreatic cancer. Methods: Pts received 8 grams of curcumin (Sabinsa Corporation) by mouth daily concurrently with gemcitabine 1000 mg/m2 IV weekly ×3 out of 4 weeks. Time to tumor progression (TTP) was the primary endpoint and toxicity profile the main secondary endpoint. Results: Seventeen pts (M:F 10:7, median age 69, range 54–78) were enrolled from 11/04 to 4/06. Six pts had locally advanced tumor and 11 pts had metastatic disease, all in liver. Pts received a median of 2 (range 1/3–14) cycles of gemcitabine. Five pts (29%) discontinued curcumin after few days to 2 weeks due to intractable abdominal fullness or pain. One pt died during 1st cycle due to unrelated cardiac event. In 11 pts curcumin and gemcitabine were delivered concomitantly for a period of 1 to 12 months. Dose of curcumin was reduced to 4 gram/day in 3 of them becuse of abdominal complains. There were 1 pt with grade II neutropenia and 1 with grade I thrombocytopenia. No other toxicities have been obsereved. One pt out of the 11 evaluable pts (9%) had partial response (7 months), 4 (36%) had stable disease (2, 3, 6 and 12 months) and 6 (55%) had tumor progression. TTP was 1 to 12 months ( median 2), and overall survival 1 to 24 months ( median 6). Conclusions: Our preliminary results suggest that a combination of gemcitabine and curcumin for pts with advanced pancreatic cancer is feasible. However, daily oral dose of curcumin should be less than 8 grams per day. Further studies need to be conducted in order to evaluate the ability of curcumin to enhance the chemotherapeutic efficacy of gemcitabine in cancer pts. No significant financial relationships to disclose.