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A multicenter phase II trial of gemcitabine and candesartan combination therapy in patients with advanced pancreatic cancer: GECA2

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Summary

Background Our retrospective study and phase I trial of gemcitabine and candesartan combination therapy suggested the inhibition of renin-angiotensin system potentially has a role in the treatment of advanced pancreatic cancer. The aim of this multicenter phase II trial was to assess the efficacy and toxicity of gemcitabine and candesartan combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naive patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m2 over 30 min on days 1, 8, and 15 and oral candesartan at a dose of 16 mg in normotensive patients, and 8 mg initially in hypertensive patients, with dose escalation to 16 mg allowed, from days 1 to 28, repeated every 4 weeks. Results A total of 35 patients with advanced pancreatic cancer were enrolled. Overall response rate and disease control rate were 11.4 % and 62.9 %. The median PFS and OS were 4.3 and 9.1 months with 1-year survival rate of 34.2 %. The median PFS was significantly longer in patients receiving 16 mg compared with 8 mg of candesartan (4.6 vs. 3.5 months, p = 0.031). Major severe toxicities were neutropenia (23 %), leukopenia (17 %) and thrombocytopenia (11 %). Grade 2 hypotension was observed in 3 patients (9 %) and candesartan was discontinued in 2 patients due to hypotension. Conclusions In this multicenter phase 2 trial, gemcitabine and candesartan combination therapy was tolerable but failed to demonstrate activity against advanced pancreatic cancer. (UMIN CTR: UMIN000005580)

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Acknowledgments

We thank Drs. Dai Mohri, Syuhei Kawahata, Tomotaka Saito, Takeo Watanabe, at Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo for the care of patients, and Drs. Ryo Nakata at Japanese Red Cross Medical Center, Kei Ogura at Tokyo Metropolitan Police Hospital, Takao Kawase at Kanto Central Hospital, Makoto Okamoto at JR Tokyo General Hospital and Nobuo Toda at Mitsui Memorial Hospital for the support.

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The authors have declared no conflicts of interest

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, Japan, 113-8655

    Yousuke Nakai, Hiroyuki Isayama, Hideaki Ijichi, Takashi Sasaki, Naminatsu Takahara, Tsuyoshi Hamada, Koji Miyabayashi, Suguru Mizuno, Keisuke Yamamoto, Hirofumi Kogure, Natsuyo Yamamoto, Kenji Hirano, Naoki Sasahira, Keisuke Tateishi, Minoru Tada & Kazuhiko Koike

  2. Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan

    Yukiko Ito

  3. Department of Gastroenterology, Tokyo Metropolitan Police Hospital, Tokyo, Japan

    Saburo Matsubara

  4. Department of Gastroenterology, Kanto Central Hospital, Tokyo, Japan

    Rie Uchino

  5. Department of Gastroenterology, JR Tokyo General Hospital, Tokyo, Japan

    Hiroshi Yagioka

  6. Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan

    Toshihiko Arizumi

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  1. Yousuke Nakai
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Correspondence to Hiroyuki Isayama.

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Nakai, Y., Isayama, H., Ijichi, H. et al. A multicenter phase II trial of gemcitabine and candesartan combination therapy in patients with advanced pancreatic cancer: GECA2. Invest New Drugs 31, 1294–1299 (2013). https://doi.org/10.1007/s10637-013-9972-5

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  • DOI: https://doi.org/10.1007/s10637-013-9972-5

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