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Phase I trial of oral S-1 combined with gemcitabine and cisplatin for advanced biliary tract cancer (KHBO1002)

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Abstract

Purpose

We aimed to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the addition of S-1, an oral fluorouracil derivative, to gemcitabine and cisplatin combination therapy, which is the current standard treatment for advanced biliary tract cancer.

Methods

Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were eligible for inclusion. The planned dosages of gemcitabine (mg/m2)/cisplatin (mg/m2)/S-1 (mg/m2/day) were as follows: level 0, 800/25/60; level 1, 1,000/25/60; and levels 2 and 3, 1,000/25/80. In each cycle, gemcitabine and cisplatin were intravenously administered on day 1 (or days 1 and 8 at level 3), and S-1 was orally administered twice daily on days 1–7 (or days 1–14 at level 3); this was repeated every 14 days (or 21 days at level 3).

Results

Seventeen patients were enrolled, and level 1 was chosen as the starting dose. Two of six patients developed DLTs (grade 4 neutropenia and grade 3 febrile neutropenia) at level 1, and the dose was escalated to level 2. DLTs (grade 3 rashes and grade 3 vasovagal reactions) occurred in two of six assessable patients at level 2; we then proceeded to level 3. The first three assessable patients enrolled at level 3 developed DLTs (two cases of grade 4 neutropenia, one of grade 4 leucopenia, two of grade 3 fatigue, one of grade 3 anorexia, and one of grade 3 febrile neutropenia) during their first cycle, and this dose was determined to be the MTD. Therefore, we selected level 2 as the recommended dose (RD) for a subsequent phase II study.

Conclusions

We determined the RD of gemcitabine/cisplatin/S-1 combination therapy for advanced biliary tract cancer; we are proceeding to a phase II study to investigate the efficacy of this combination therapy for advanced biliary tract cancer.

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Acknowledgments

Tatsuya Ioka received research funding from Taiho.

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Authors and Affiliations

  1. Outpatient Oncology Unit, Kyoto University Hospital, Kyoto, Japan

    Masashi Kanai

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

    Etsuro Hatano

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

    Syogo Kobayashi & Hiroaki Nagano

  4. Department of Medical Oncology and Hematology, Kobe University Graduate School of Medicine, Kobe, Japan

    Yutaka Fujiwara

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

    Daisuke Sakai

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

    Yuzo Kodama

  7. Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan

    Tetsuo Ajiki

  8. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Tatsuya Ioka

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  1. Masashi Kanai
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  2. Etsuro Hatano
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  3. Syogo Kobayashi
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  4. Yutaka Fujiwara
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  5. Daisuke Sakai
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  9. Tatsuya Ioka
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Correspondence to Masashi Kanai.

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Kanai, M., Hatano, E., Kobayashi, S. et al. Phase I trial of oral S-1 combined with gemcitabine and cisplatin for advanced biliary tract cancer (KHBO1002). Cancer Chemother Pharmacol 69, 1181–1188 (2012). https://doi.org/10.1007/s00280-011-1818-2

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  • DOI: https://doi.org/10.1007/s00280-011-1818-2

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