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A phase II trial of gemcitabine, S-1 and LV combination (GSL) therapy in patients with advanced pancreatic cancer

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Summary

Purpose Our previous phase I trial suggested feasibility of addition of leucovorin (LV) to S-1 and gemcitabine therapy in advanced pancreatic cancer. The aim of this phase II trial was to assess the efficacy and toxicity of gemcitabine, S-1 and LV (GSL) combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naïve patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1000 mg/m2 by 30 min infusion on days 1, S-1 40 mg/m2 orally twice daily and LV 25 mg orally twice daily on days 1 to 7 every 2 weeks. Primary end point was progression free survival (PFS). Results A total of 49 patients with advanced pancreatic cancer (19 locally advanced and 30 metastatic) were enrolled. Overall response rate and disease control rate were 32.7% and 87.8%. The median PFS and overall survival (OS) were 10.8 (95% confidence interval [CI], 7.4–13.5) and 20.7 (95% CI 13.0-NA) months with 1-year survival rate of 73.4%. Major Grade 3–4 toxicities were neutropenia (22.4%) and stomatitis (14.3%). No toxicity related death was observed. Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer.

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Acknowledgments

The authors would like to thank Drs. Dai Akiyama, Kaoru Takagi, Takeo Watanabe, Ryouta Takahashi, Dai Mohri and Kenji Hirano for their patient management.

Funding

This research was supported by Japanese foundation for multidisciplinary treatment of cancer.

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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, 113-8655, Japan

    Kei Saito, Hiroyuki Isayama, Yousuke Nakai, Naminatsu Takahara, Kazunaga Ishigaki, Tsuyoshi Takeda, Ryunosuke Hakuta, Tomotaka Saito, Rie Uchino, Takahiro Kishikawa, Tsuyoshi Hamada, Suguru Mizuno, Takashi Sasaki, Hirofumi Kogure, Saburo Matsubara, Natsuyo Yamamoto, Hideaki Ijichi, Keisuke Tateishi, Minoru Tada & Kazuhiko Koike

  2. Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan

    Hiroyuki Isayama

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  1. Kei Saito
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  2. Hiroyuki Isayama
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Corresponding author

Correspondence to Hiroyuki Isayama.

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Conflict of interest

Hiroyuki Isayama and Yousuke Nakai received research funding from Taiho Pharmaceutical Co. All remaining authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethical Committee of the University of Tokyo Hospital.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Saito, K., Isayama, H., Nakai, Y. et al. A phase II trial of gemcitabine, S-1 and LV combination (GSL) therapy in patients with advanced pancreatic cancer. Invest New Drugs 37, 338–344 (2019). https://doi.org/10.1007/s10637-018-0691-9

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  • DOI: https://doi.org/10.1007/s10637-018-0691-9

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