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A multi-institution phase II study of gemcitabine/cisplatin/S-1 (GCS) combination chemotherapy for patients with advanced biliary tract cancer (KHBO 1002)

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Abstract

Purpose

Gemcitabine/cisplatin combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). We aimed to evaluate the efficacy and safety of adding S-1 to gemcitabine/cisplatin combination therapy for patients with advanced BTC.

Methods

Patients with histologically or cytologically confirmed unresectable or recurrent BTC were eligible for inclusion. The primary end point was overall survival. Based on the results of our preceding phase I study, gemcitabine and cisplatin were administered intravenously at doses of 1,000 or 25 mg/m2, respectively, on day 1, and oral S-1 was administered daily at a dose of 80 mg/m2 on days 1–7 every 2 weeks. This study was registered with ClinicalTrials.gov (NCT01284413) and the UMIN Clinical Trials Registry (ID 000004468).

Results

Fifty patients enrolled between October 2011 and August 2012 were evaluated. After a median follow-up of 15.1 months (range 2.4–24.4 months), the median overall survival time was 16.2 months [95 % confidence interval (CI) 10.2–22.2 months], and the one-year overall survival rate was 59.9 % (95 % CI 46.2–73.5 %). The grade 3–4 hematological toxicities were as follows: neutropenia (32 %), anemia (32 %), thrombocytopenia (10 %), and febrile neutropenia (4 %). The common grade 3–4 non-hematological toxicities were biliary tract infection (14 %), anorexia/nausea (10 %), and fatigue (8 %).

Conclusions

Gemcitabine/cisplatin/S-1 combination chemotherapy offered a promising survival benefit with manageable toxicity in patients with advanced BTC. A randomized phase III trial to investigate the efficacy of this regimen compared to gemcitabine/cisplatin combination therapy in patients with advanced BTC is now underway (UMIN000014371/NCT02182778).

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Acknowledgments

We thank Masami Kashibou for her contributions to data management.

Conflict of interest

Honoraria Tatsuya Ioka, Eli Lilly, Taiho Pharmaceutical. Research Funding Tatsuya Ioka, Taiho Pharmaceutical.

Author information

Authors and Affiliations

  1. Department of Clinical Oncology and Pharmacogenomics, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Masashi Kanai

  2. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Etsuro Hatano & Satoru Seo

  3. Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

    Shogo Kobayashi & Hiroaki Nagano

  4. Department of Experimental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital, Tokyo, Japan

    Yutaka Fujiwara

  5. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Shigeru Marubashi

  6. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Atsushi Miyamoto

  7. Department of Surgery, Shiga University of Medical Science, Shiga, Japan

    Hisanori Shiomi

  8. Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan

    Shoji Kubo

  9. Department of Surgery, Meiwa General Hospital, Hyogo, Japan

    Shinichi Ikuta

  10. Department of Surgery, Kansai Medical University, Osaka, Japan

    Hiroaki Yanagimoto

  11. Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Osaka, Japan

    Hiroaki Terajima

  12. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Hisashi Ikoma

  13. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan

    Daisuke Sakai

  14. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University Hospital, Kyoto, Japan

    Yuzo Kodama

  15. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Satoshi Morita

  16. Department of Surgery, Graduate School of Medicine, Kobe University Hospital, Kobe, Japan

    Tetsuo Ajiki

  17. Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Tatsuya Ioka

Authors
  1. Masashi Kanai
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  2. Etsuro Hatano
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  3. Shogo Kobayashi
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  15. Satoru Seo
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  16. Satoshi Morita
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  18. Hiroaki Nagano
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  19. Tatsuya Ioka
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Corresponding author

Correspondence to Masashi Kanai.

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Kanai, M., Hatano, E., Kobayashi, S. et al. A multi-institution phase II study of gemcitabine/cisplatin/S-1 (GCS) combination chemotherapy for patients with advanced biliary tract cancer (KHBO 1002). Cancer Chemother Pharmacol 75, 293–300 (2015). https://doi.org/10.1007/s00280-014-2648-9

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