Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial.

Abstract

BACKGROUND:

Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS).

PATIENTS AND METHODS:

We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea.

RESULTS:

Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm.

CONCLUSIONS:

GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC.

CLINICAL TRIAL NUMBER:

This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.

• Authors: C Morizane, T Okusaka, J Mizusawa, H Katayama, M Ueno, M Ikeda, M Ozaka, N Okano, K Sugimori, A Fukutomi, H Hara, N Mizuno, H Yanagimoto, K Wada, K Tobimatsu, K Yane, S Nakamori, H Yamaguchi, A Asagi, S Yukisawa, Y Kojima, K Kawabe, Y Kawamoto, R Sugimoto, T Iwai, K Nakamura, H Miyakawa, T Yamashita, A Hosokawa, T Ioka, N Kato, K Shioji, K Shimizu, T Nakagohri, K Kamata, H Ishii, J Furuse, members of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG)
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 30 Issue 12 Pg. 1950-1958 (12 01 2019) ISSN: 1569-8041 [Electronic] England
• PMID: 31566666 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

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

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Biliary Tract Neoplasms (drug therapy, epidemiology, pathology)
• Cisplatin (administration & dosage, adverse effects)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Disease-Free Survival
• Drug Combinations
• Female
• Humans
• Japan (epidemiology)
• Male
• Middle Aged
• Nausea (chemically induced, pathology)
• Oxonic Acid (administration & dosage, adverse effects)
• Tegafur (administration & dosage, adverse effects)
• Vomiting (chemically induced, pathology)
• Gemcitabine