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Phase II study of fixed dose-rate gemcitabine plus S-1 as a second-line treatment for advanced biliary tract cancer

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Abstract

Purpose

Gemcitabine plus platinum is considered standard first-line chemotherapy for patients with advanced biliary tract cancer. However, no standard second-line therapy has been established for this disease. According to reports, S-1 exerts anti-tumor effects on advanced biliary tract cancer and gemcitabine is more effective via fixed dose-rate administration. We evaluated the efficacy and safety of a combination of fixed dose-rate gemcitabine and S-1 after failure of gemcitabine or gemcitabine plus cisplatin therapy.

Methods

This single-arm phase II study (clinical trial number: UMIN000005918) set the response rate as the primary endpoint and used a MiniMax two-stage design with a null hypothesis < 7% and alternative hypothesis ≥ 25%. Thirty-five patients were needed to yield a power of 90% and α value of 0.05. Patients received gemcitabine (1000 mg/m2, div, 100-min period, day 1) and S-1 (40 mg/m2 twice daily, oral, days 1–7), every 2 weeks until disease progression or intolerable adverse events were observed.

Results

Forty-one patients were enrolled, and 3 of 23 first-stage patients responded. The overall response rate was 9.8% [95% confidence interval (CI): 2.7–19.2%]. The median overall and progression-free survival were 7.0 [95% CI: 5.3–8.6] and 2.6 months (95% CI: 1.6–3.5), respectively. The most common grade 3–4 adverse events were leukopenia (19.5%), neutropenia (19.5%), anemia (14.6%), thrombocytopenia (7.3%), and anorexia (4.8%).

Conclusion

Second-line fixed dose-rate gemcitabine plus S-1 was not sufficiently effective and tolerable in patients with advanced biliary tract cancer refractory to gemcitabine or gemcitabine plus cisplatin.

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Authors and Affiliations

  1. Hepatobiliary and Pancreatic Oncology Division, Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan

    Satoshi Kobayashi, Makoto Ueno, Kuniyasu Irie, Yoshihiro Goda, Manabu Morimoto & Shinichi Ohkawa

  2. Department of Gastroenterology, Yokohama City University Medical Center, Yokohama, Japan

    Kazuya Sugimori

  3. Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan

    Chigusa Morizane

  4. Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan

    Yasushi Kojima

Authors
  1. Satoshi Kobayashi
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  2. Makoto Ueno
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  3. Kazuya Sugimori
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  4. Chigusa Morizane
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  5. Yasushi Kojima
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  6. Kuniyasu Irie
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  7. Yoshihiro Goda
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  8. Manabu Morimoto
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  9. Shinichi Ohkawa
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Corresponding author

Correspondence to Satoshi Kobayashi.

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Funding

This research was supported by Grants awarded to the Kanagawa Cancer Center by: Taiho Pharmaceutical Co., Ltd.; Eli Lilly and Company; Yakult Honsha Co., Ltd.; and Daiichi-Sankyo Co., Ltd.

Conflict of interest

S. Kobayashi received honorariums for the development of an educational presentation from Taiho Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.; Pfizer Inc.; and AstraZeneca plc. M. Ueno received honorariums for the development of an educational presentation from Taiho Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.; Eli Lilly and Company; AstraZeneca plc; Kyowa Hakko Kirin Co., Ltd.; Boston Scientific Corporation; Abbott Laboratories; and Novartis.

Research involving human participants

This study was conducted in accordance with the Helsinki Declaration and Good Clinical Practices and was approved by the institutional review board at each hospital. The study has been registered with UMIN Clinical Trials Registry (no.: UMIN000005918).

Informed consent

We obtained written informed consent from all patients prior to participation.

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Kobayashi, S., Ueno, M., Sugimori, K. et al. Phase II study of fixed dose-rate gemcitabine plus S-1 as a second-line treatment for advanced biliary tract cancer. Cancer Chemother Pharmacol 80, 1189–1196 (2017). https://doi.org/10.1007/s00280-017-3461-z

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