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Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial

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Abstract

Background

Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1.

Methods

We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I–III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility.

Results

A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841–1.553; P  =  0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727–1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310–1.105; P  = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively).

Conclusions

In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.

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Acknowledgements

We thank Eisuke Adachi (Kyushu Central Hospital) and Yasuharu Ikeda (Fukuoka City Hospital) for the data and safety monitoring. We thank Jane Charbonneau, DVM, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan

    Hiroto Kayashima, Shinji Itoh & Tomoharu Yoshizumi

  2. Department of Biostatistics, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8511, Japan

    Mototsugu Shimokawa

  3. Department of Gastroenterological Surgery, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Hiromitsu Hayashi & Hideo Baba

  4. Department of Surgery, Saiseikai Kumamoto Hospital, 5-3-1 Chikami, Kumamoto, 861-4193, Japan

    Hiroshi Takamori

  5. Department of Surgery, Oita Red Cross Hospital, 3-2-37 Chiyo-machi, Oita, 870-0033, Japan

    Kengo Fukuzawa

  6. Department of Surgery, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan

    Mizuki Ninomiya

  7. Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, 4-2 Aramaki-machi, Maebashi, Gunma, 371-8510, Japan

    Kenichiro Araki

  8. Department of Surgery, Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan

    Yo-ichi Yamashita

  9. Department of Hepatobiliary-Pancreatic Surgery, Kyushu Cancer Center, 3-1-1 Notame, Fukuoka, 811-1395, Japan

    Keishi Sugimachi

  10. Department of Surgery, Saiseikai Fukuoka General Hospital, 1-3-46 Tenjin, Fukuoka, 810-0001, Japan

    Hideaki Uchiyama

  11. Department of Surgery, Tokushima University, 2-24 Shinkuracho, Tokushima, 770-0855, Japan

    Yuji Morine

  12. Department of Surgery, Oita Prefectural Hospital, 2-8-1 Bunyo, Oita, 870-8511, Japan

    Tohru Utsunomiya

  13. Department of Hepato-Biliary-Pancreatic Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan

    Tadashi Uwagawa

  14. Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, 1-9-6 Senda-machi, Hiroshima, 730-8619, Japan

    Takashi Maeda

Authors
  1. Hiroto Kayashima
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  2. Shinji Itoh
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  3. Mototsugu Shimokawa
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  4. Hiromitsu Hayashi
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  5. Hiroshi Takamori
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  6. Kengo Fukuzawa
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  7. Mizuki Ninomiya
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  8. Kenichiro Araki
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  9. Yo-ichi Yamashita
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  10. Keishi Sugimachi
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  11. Hideaki Uchiyama
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  12. Yuji Morine
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  13. Tohru Utsunomiya
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  14. Tadashi Uwagawa
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  15. Takashi Maeda
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  16. Hideo Baba
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  17. Tomoharu Yoshizumi
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Contributions

HK: conceptualisation, data curation, methodology, formal analysis, investigation, resources, visualisation, writing – original draft, writing—review & editing. SI: conceptualisation, data curation, methodology, formal analysis, investigation, resources, visualization, project administration, writing—original draft, writing—review & editing. MS: conceptualisation, data curation, methodology, formal analysis, validation, writing—original draft, writing—review & editing. HH, HT, KF, MN, KA, Y-iY, KS, HU, YM, TU, TU, TM, HB: investigation, resources, writing—review & editing. TY: conceptualisation, methodology, project administration, supervision, writing—review & editing.

Corresponding author

Correspondence to Shinji Itoh.

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Conflict of interest

All authors declare no conflicts of interest regarding this article.

Ethical approval

The study protocol was approved by Kyushu University Hospital Institutional Review Board (Approval number: 25066). This trial was completed in accordance with the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies of the Ministry of Health, Labour, and Welfare of Japan.

Informed consent

Informed consent was obtained from all patients for inclusion in the study.

Registration number

This study was registered at University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000012634 (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014772).

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Kayashima, H., Itoh, S., Shimokawa, M. et al. Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial. Int J Clin Oncol 28, 1520–1529 (2023). https://doi.org/10.1007/s10147-023-02399-7

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  • DOI: https://doi.org/10.1007/s10147-023-02399-7

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