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A phase I/II study of fixed-dose-rate gemcitabine and S-1 with concurrent radiotherapy for locally advanced pancreatic cancer

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Abstract

Purpose

This study was conducted to identify the maximum-tolerated dose (MTD) of fixed-dose-rate gemcitabine (FDR-gem) administered concurrently with S-1 and radical radiation for locally advanced pancreatic cancer (LAPC) and to provide efficacy and safety data.

Methods

Patients with unrespectable pancreatic cancer confined to the pancreatic region were treated with FDR-gem (300–400 mg/m2, 5 mg/m2/min) on days 1, 8, 22, and 29 and 60 mg/m2 of S-1 orally on days 1–14, 22–35. A total radiation dose of 50.4 Gy (1.8 Gy/day, 28 fractions) was delivered concurrently.

Results

Twenty-five patients were enrolled; all were evaluable for toxicity assessment. In phase I, eight patients were treated in sequential cohorts of three to five patients per dose level. The MTD was reached at level 2, and dose-limiting toxicities were neutropenia and thrombocytopenia. The recommended doses were 300 mg/m2 of gemcitabine and 60 mg/m2 of S-1 daily. The overall response rate was 25 % and disease control rate (partial response plus stable disease) was 92 %. The progression-free survival was 11.0 months. The median overall survival and 1-year survival rates were 16.0 months and 73 %, respectively.

Conclusion

The combination of FDR-gem and S-1 with radiation is a feasible regimen that shows favorable antitumor activity with an acceptable safety profile in patients with LAPC.

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Authors and Affiliations

  1. Department of Gastroenterology and Oncology, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan

    Takahiro Goji, Tetsuo Kimura, Hiroshi Miyamoto, Masanori Takehara, Kaizo Kagemoto, Yasuyuki Okada, Jun Okazaki, Yoshifumi Takaoka, Yoshihiko Miyamoto, Yasuhiro Mitsui, Sayo Matsumoto, Tatsuhisa Sueuchi, Kumiko Tanaka, Yasuteru Fujino, Toshi Takaoka, Shinji Kitamura, Koichi Okamoto, Masako Kimura, Masahiro Sogabe, Naoki Muguruma, Toshiya Okahisa & Tetsuji Takayama

  2. Department of Gastroenterology, Hokkaido Cancer Center, National Hospital Organization, 4-2-3-54 Shiraishi-ku, Kikusui, Sapporo, Hokkaido, 003-0804, Japan

    Yasuhiro Sato, Tamotsu Sagawa & Koji Fujikawa

  3. Fourth Department of Internal Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan

    Yasushi Sato

  4. Department of Radiation Therapy Technology, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan

    Hitoshi Ikushima

Authors
  1. Takahiro Goji
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  2. Tetsuo Kimura
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  3. Hiroshi Miyamoto
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  4. Masanori Takehara
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  5. Kaizo Kagemoto
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  6. Yasuyuki Okada
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  7. Jun Okazaki
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  8. Yoshifumi Takaoka
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  9. Yoshihiko Miyamoto
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  10. Yasuhiro Mitsui
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  11. Sayo Matsumoto
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  12. Tatsuhisa Sueuchi
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  13. Kumiko Tanaka
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  14. Yasuteru Fujino
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  15. Toshi Takaoka
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  16. Shinji Kitamura
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  17. Koichi Okamoto
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  18. Masako Kimura
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  19. Masahiro Sogabe
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  20. Naoki Muguruma
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  21. Toshiya Okahisa
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  22. Yasuhiro Sato
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  23. Tamotsu Sagawa
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  24. Koji Fujikawa
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  25. Yasushi Sato
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  26. Hitoshi Ikushima
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  27. Tetsuji Takayama
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Corresponding author

Correspondence to Tetsuji Takayama.

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Conflict of interest

Tetsuji Takayama has received honoraria from Taiho Pharmaceutical Co. Ltd. All other authors declare that they have no conflict of interest relevant to this study.

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Goji, T., Kimura, T., Miyamoto, H. et al. A phase I/II study of fixed-dose-rate gemcitabine and S-1 with concurrent radiotherapy for locally advanced pancreatic cancer. Cancer Chemother Pharmacol 76, 615–620 (2015). https://doi.org/10.1007/s00280-015-2835-3

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  • DOI: https://doi.org/10.1007/s00280-015-2835-3

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