A feasibility study of gemcitabine, S-1 and leucovorin combination therapy (GSL) for advanced biliary tract cancer

Naminatsu Takahara, Hiroyuki Isayama, Yousuke Nakai, Takashi Sasaki, Kei Saito, Tatsuya Sato, Ryunosuke Hakuta, Kazunaga Ishigaki, Tomotaka Saito, Tsuyoshi Hamada, Suguru Mizuno, Hirofumi Kogure, Minoru Tada, Kazuhiko Koike

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2 Citations (Scopus)


Objective: Gemcitabine and cisplatin (GC) combination chemotherapy is the current standard of care for patients with advanced biliary tract cancer (BTC). Recently, a randomized controlled trial showed the non-inferiority in overall survival of gemcitabine and S-1 (GS) compared to GC. Because leucovorin is known to enhance the activity of S-1, we conducted this study to evaluate the feasibility of combination therapy of gemcitabine, S-1 and leucovorin (GSL). Methods: Advanced BTC patients without prior treatment other than surgery or adjuvant chemotherapy were eligible to this study. Gemcitabine was administered at a dose of 1000 mg/m2 on day 1, and oral S-1 at a dose of 40 mg/m2 and oral leucovorin at a dose of 25 mg twice daily on days 1–7, every 2 weeks. The primary endpoint was PFS and the secondary endpoints included OS, objective tumour response and the safety. Results: Between June 2013 and December 2015, 20 patients with advanced BTC (12 gallbladder, 4 extrahepatic, 2 intrahepatic, 2 ampulla) including 16 unresectable disease and 4 recurrent disease were enroled. The median PFS and OS were 5.5 (95% confidence interval [CI], 1.8–not reached) and 16.0 (95% CI, 6.4–20.8) months, respectively. A partial response was achieved in 3 (15%) and stable disease in 8 (40%), giving a disease control rate of 55%. Major grade 3/4 toxicities included neutropenia (30%), anaemia (5%), stomatitis (15%), diarrhoea (15%) and anorexia (10%). There were no treatment-related deaths. Conclusions: This study showed the feasibility and potential efficacy of GSL as a first-line treatment in patients with advanced BTC.

Original languageEnglish
Pages (from-to)284-289
Number of pages6
JournalJournal of Chemotherapy
Issue number5
Publication statusPublished - 2019
Externally publishedYes


  • Biliary tract cancer
  • S-1
  • first-line chemotherapy
  • gemcitabine
  • leucovorin
  • pilot study


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