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

Abstract

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.

• Authors: 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
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 31 Issue 5 Pg. 284-289 (Sep 2019) ISSN: 1973-9478 [Electronic] England
• PMID: 31179889 (Publication Type: Journal Article)

Chemical References

• Drug Combinations
• Deoxycytidine
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Leucovorin
• Gemcitabine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biliary Tract Neoplasms (drug therapy, pathology)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Drug Combinations
• Feasibility Studies
• Female
• Follow-Up Studies
• Humans
• Leucovorin (administration & dosage)
• Liver Neoplasms (drug therapy, secondary)
• Lung Neoplasms (drug therapy, secondary)
• Lymphatic Metastasis
• Male
• Middle Aged
• Oxonic Acid (administration & dosage)
• Peritoneal Neoplasms (drug therapy, secondary)
• Prognosis
• Survival Rate
• Tegafur (administration & dosage)
• Gemcitabine