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Phase 1 study of Gemcitabine/Nab-paclitaxel/S-1 in patients with unresectable pancreatic cancer (GeNeS1S trial)

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Abstract

Purpose

We conducted a phase 1 study to determine the maximum tolerated dose and the recommended dose of gemcitabine/nab-paclitaxel/S-1 combination chemotherapy in patients with unresectable pancreatic cancer.

Methods

We enrolled patients aged 20 years or older with unresectable pancreatic cancer and who had not been treated with chemotherapy or radiation therapy. Gemcitabine and nab-paclitaxel were administered on days 1 and 8, and S-1 was administered orally twice daily for 2 weeks, repeated every 3 weeks. The starting dose was level 0 [gemcitabine 700 mg/m2, nab-paclitaxel 90 mg/m2, S-1 60/80/100 mg/day (< 1.25 m2/1.25–1.50 m2/ > 1.5 m2)]. Dose-limiting toxicities were determined during the first course, and a classical 3 + 3 dose finding design was planned.

Results

From March 2018 to October 2019, 20 patients were enrolled. At dose level 0, three of six patients experienced dose-limiting toxicities; one grade 3 skin rash on day 8, and two grade 3 or 4 neutropenia on day 8. At dose level-1 (gemcitabine 600 mg/m2, nab-paclitaxel 90 mg/m2, and S-1 50/70/80 mg/day), two of twelve patients experienced dose-limiting toxicities, all of which were grade 3 neutropenia on day 8. The most frequently observed toxicity during eight courses was neutropenia. Other treatment-related adverse events were mild. Eleven out of 19 (58%) patients achieved partial response.

Conclusion

We defined the maximum tolerated dose and the recommended dose for combination therapy with gemcitabine/nab-paclitaxel/S-1 as dose level-1. Considering the observed response rate, further studies are warranted in order to determine the efficacy of this regimen (UMIN-CTR 000030007).

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Funding

No funding was received for conducting this study.

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Authors and Affiliations

  1. Department of Medical Oncology/Hematology, Kobe University Hospital and Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

    Satoshi Sai, Masanori Toyoda, Shiro Kimbara, Taiji Koyama, Yoshimi Fujishima, Yoshinori Imamura, Yohei Funakoshi, Naomi Kiyota & Hironobu Minami

  2. Department of Gastroenterology, Kobe University Hospital and Graduate School of Medicine, Kobe, Japan

    Kazutoshi Tobimatsu & Yuzo Kodama

  3. Department of Medical Oncology, Kobe City Hospital Organization, Kobe City Medical Center General Hospital, Kobe, Japan

    Hironaga Satake & Hisateru Yasui

  4. Cancer Center, Kobe University Hospital, Kobe, Japan

    Naomi Kiyota & Hironobu Minami

  5. Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Hospital and Graduate School of Medicine, Kobe, Japan

    Hirochika Toyama

Authors
  1. Satoshi Sai
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  2. Masanori Toyoda
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  3. Kazutoshi Tobimatsu
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  4. Hironaga Satake
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  5. Hisateru Yasui
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  6. Shiro Kimbara
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  7. Taiji Koyama
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  8. Yoshimi Fujishima
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  9. Yoshinori Imamura
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  10. Yohei Funakoshi
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  11. Naomi Kiyota
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  12. Hirochika Toyama
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  13. Yuzo Kodama
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  14. Hironobu Minami
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Contributions

All authors have contributed significantly, and all authors are in agreement with the content of the manuscript.

Corresponding author

Correspondence to Masanori Toyoda.

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Conflict of interest

Masanori Toyoda has received a honoraria from Taiho Pharmaceutical Co., Ltd. Hironaga Satake has received a research grant from Taiho Pharmaceutical Co., Ltd, a honoraria from Eli Lilly Japan Co., Ltd. and Taiho Pharmaceutical Co., Ltd. Hisateru Yasui has received a honoraria from Eli Lilly Japan Co., Ltd. and Taiho Pharmaceutical Co., Ltd. Hironobu Minami has received a research grant and personal fees from Eli Lilly Japan Co., Ltd. and Taiho Pharmaceutical Co., Ltd. The remaining authors have no conflict of interest to declare.

Ethical approval

This study was conducted in compliance with the ethical principles of the Declaration of Helsinki, the principles of Good Clinical Practice and all applicable regulations. The study protocol was approved by the institutional review board of each participating institution, and written informed consent was obtained from all participants.

Informed consent

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

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Patients signed informed consent regarding publishing their data.

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Sai, S., Toyoda, M., Tobimatsu, K. et al. Phase 1 study of Gemcitabine/Nab-paclitaxel/S-1 in patients with unresectable pancreatic cancer (GeNeS1S trial). Cancer Chemother Pharmacol 87, 65–71 (2021). https://doi.org/10.1007/s00280-020-04174-1

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  • DOI: https://doi.org/10.1007/s00280-020-04174-1

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