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Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer

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Abstract

Purpose

For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen.

Methods

Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined. Patients were classified according to the designated dose levels of chemoradiotherapy using the GnP regimen. After additional 6 cycles of the GnP regimen were administered, surgery was considered if the patients had stable disease and tumor marker levels had normalized.

Results

DLT (grade 4 thrombocytopenia) was observed only in 1 of 12 patients, and the RD was set at level 3. Grade 3–4 leukopenia was observed in 9 (75.0%) patients, and neutropenia in 7 (58.3%). The response rate was 41.7%, and the disease control rate was 100%. Conversion surgery was performed in 6 (50%) patients, and curative resection (R0) was performed in all 6 patients (100%). Stratification according to the Evans classification system demonstrated one patient with grade 1b, one with grade 2, two with grade 3, and two with grade 4 disease.

Conclusion

The RD for weekly administration was 800 mg/m2 for gemcitabine and 100 mg/m2 for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.

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Acknowledgements

We are deeply grateful to the members in Nagoya University cancer board of pancreatic cancer.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Suguru Yamada, Nao Takano, Hideki Takami, Masamichi Hayashi, Yukiko Niwa & Yasuhiro Kodera

  2. Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Tsutomu Fujii

  3. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yukihiro Yokoyama, Junpei Yamaguchi & Masato Nagino

  4. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Hiroki Kawashima & Hidemi Goto

  5. Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan

    Osamu Maeda & Yuichi Ando

  6. Department of Radiology, Aichi Medical University, Nagakute, Aichi, Japan

    Kojiro Suzuki

  7. Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Tohru Okada, Yoshiyuki Ito & Shinji Naganawa

  8. Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan

    Eizaburo Ono & Yoshiki Hirooka

Authors
  1. Suguru Yamada
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  2. Tsutomu Fujii
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  3. Yukihiro Yokoyama
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  4. Hiroki Kawashima
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  5. Osamu Maeda
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  6. Kojiro Suzuki
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  7. Tohru Okada
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  8. Eizaburo Ono
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  9. Junpei Yamaguchi
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  10. Nao Takano
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  11. Hideki Takami
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  12. Masamichi Hayashi
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  13. Yukiko Niwa
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  14. Yoshiki Hirooka
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  15. Yoshiyuki Ito
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  16. Shinji Naganawa
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  17. Yuichi Ando
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  18. Masato Nagino
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  19. Hidemi Goto
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  20. Yasuhiro Kodera
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Corresponding author

Correspondence to Suguru Yamada.

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Conflict of interest

All authors in this study have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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

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Yamada, S., Fujii, T., Yokoyama, Y. et al. Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer. Cancer Chemother Pharmacol 81, 815–821 (2018). https://doi.org/10.1007/s00280-018-3554-3

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  • DOI: https://doi.org/10.1007/s00280-018-3554-3

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