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Investigational New Drugs

, Volume 31, Issue 5, pp 1294–1299 | Cite as

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

  • Yousuke Nakai
  • Hiroyuki Isayama
  • Hideaki Ijichi
  • Takashi Sasaki
  • Naminatsu Takahara
  • Yukiko Ito
  • Saburo Matsubara
  • Rie Uchino
  • Hiroshi Yagioka
  • Toshihiko Arizumi
  • Tsuyoshi Hamada
  • Koji Miyabayashi
  • Suguru Mizuno
  • Keisuke Yamamoto
  • Hirofumi Kogure
  • Natsuyo Yamamoto
  • Kenji Hirano
  • Naoki Sasahira
  • Keisuke Tateishi
  • Minoru Tada
  • Kazuhiko Koike
PHASE II STUDIES

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)

Keywords

Candesartan Chemotherapy Gemcitabine Renin-angiotensin system Pancreatic cancer 

Notes

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.

Disclosures

The authors have declared no conflicts of interest

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yousuke Nakai
    • 1
  • Hiroyuki Isayama
    • 1
  • Hideaki Ijichi
    • 1
  • Takashi Sasaki
    • 1
  • Naminatsu Takahara
    • 1
  • Yukiko Ito
    • 2
  • Saburo Matsubara
    • 3
  • Rie Uchino
    • 4
  • Hiroshi Yagioka
    • 5
  • Toshihiko Arizumi
    • 6
  • Tsuyoshi Hamada
    • 1
  • Koji Miyabayashi
    • 1
  • Suguru Mizuno
    • 1
  • Keisuke Yamamoto
    • 1
  • Hirofumi Kogure
    • 1
  • Natsuyo Yamamoto
    • 1
  • Kenji Hirano
    • 1
  • Naoki Sasahira
    • 1
  • Keisuke Tateishi
    • 1
  • Minoru Tada
    • 1
  • Kazuhiko Koike
    • 1
  1. 1.Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Department of GastroenterologyJapanese Red Cross Medical CenterTokyoJapan
  3. 3.Department of GastroenterologyTokyo Metropolitan Police HospitalTokyoJapan
  4. 4.Department of GastroenterologyKanto Central HospitalTokyoJapan
  5. 5.Department of GastroenterologyJR Tokyo General HospitalTokyoJapan
  6. 6.Department of GastroenterologyMitsui Memorial HospitalTokyoJapan

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