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Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 1, pp 157–164 | Cite as

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

  • Masashi KanaiEmail author
  • Kenichi Yoshimura
  • Masanori Asada
  • Atsushi Imaizumi
  • Chihiro Suzuki
  • Shigemi Matsumoto
  • Takafumi Nishimura
  • Yukiko Mori
  • Toshihiko Masui
  • Yoshiya Kawaguchi
  • Kazuhiro Yanagihara
  • Shujiro Yazumi
  • Tsutomu Chiba
  • Sushovan Guha
  • Bharat B. Aggarwal
Original Article

Abstract

Purpose

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.

Methods

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.

Results

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 No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral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.

Conclusions

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.

Keywords

Curcumin Gemcitabine Pancreatic cancer 

Notes

Acknowledgments

We thank Hiroe Tada and Miyuki Niimi for their contributions to data management, Emi Shimada, and Dr Vladimir Badmaev for their contributions to curcumin shipment. This work was supported by the Grant-in-Aid for Young Scientists (21790661) from the Japan Society for the Promotion of Science, Japanese Research Foundation for Clinical Pharmacology and Smoking Research Foundation.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Masashi Kanai
    • 1
    Email author
  • Kenichi Yoshimura
    • 2
  • Masanori Asada
    • 3
  • Atsushi Imaizumi
    • 4
  • Chihiro Suzuki
    • 2
  • Shigemi Matsumoto
    • 1
  • Takafumi Nishimura
    • 1
  • Yukiko Mori
    • 1
  • Toshihiko Masui
    • 5
  • Yoshiya Kawaguchi
    • 5
  • Kazuhiro Yanagihara
    • 1
  • Shujiro Yazumi
    • 3
  • Tsutomu Chiba
    • 1
    • 6
  • Sushovan Guha
    • 7
  • Bharat B. Aggarwal
    • 8
  1. 1.Outpatient Oncology UnitKyoto University HospitalKyotoJapan
  2. 2.Translational Research Center, Kyoto University HospitalKyotoJapan
  3. 3.Kitano HospitalOsakaJapan
  4. 4.Theravalues CorporationTokyoJapan
  5. 5.Department of Surgery, Graduate School of MedicineKyoto University HospitalKyotoJapan
  6. 6.Department of Gastroenterology and HepatologyKyoto University HospitalKyotoJapan
  7. 7.Department of Gastrointestinal Medicine and NutritionMD Anderson Cancer CenterHoustonUSA
  8. 8.Department of Experimental TherapeuticsMD Anderson Cancer CenterHoustonUSA

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