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Allen et al. Hepatoma Res 2021;7:73 Hepatoma Research
DOI: 10.20517/2394-5079.2021.98

Review Open Access

A review of current adjuvant and neoadjuvant

systemic treatments for cholangiocarcinoma and
gallbladder carcinoma

Michael J. Allen, Jennifer J. Knox

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto ON M5G 2M9, ON, Canada.
Correspondence to: Dr. Jennifer J. Knox, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610
University Avenue, Toronto M5G 2M9, ON, Canada. E-mail: Jennifer.Knox@uhn.ca
How to cite this article: Allen MJ, Knox JJ. A review of current adjuvant and neoadjuvant systemic treatments for
cholangiocarcinoma and gallbladder carcinoma. Hepatoma Res 2021;7:73. https://dx.doi.org/10.20517/2394-5079.2021.98
Received: 26 Jul 2021 First Decision: 30 Aug 2021 Revised: 8 Sep 2021 Accepted: 11 Oct 2021 Published: 5 Nov 2021

Academic Editor: Allan Tsung Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
Biliary tract cancers are a relatively rare heterogenous group of malignancies, including gallbladder cancer,
intrahepatic, perihilar, and distal cholangiocarcinoma. Most patients are diagnosed with locally advanced or
metastatic disease, and survival outcomes remain poor. This is also the case in the relatively few who undergo
curative surgery. Efforts to improve patient survival outcomes have focussed on adjuvant and neoadjuvant
chemotherapy and chemoradiotherapy. Adjuvant trials investigating the efficacy of systemic chemotherapy have
primarily been negative to date, with challenges including compliance, recruitment rate, percentage of node-
positive and R1 resections, and tumor heterogenicity observed. As reported in BILCAP, adjuvant capecitabine is
currently considered the standard of care in many countries and guidelines, while chemoradiotherapy improves R1
outcomes as observed in the phase II trial SWOG S0809. Trials are ongoing to elicit the ideal combination of
adjuvant treatment. Evidence for neoadjuvant chemotherapy continues to be based on retrospective analysis and a
few phase II trials, with observed downstaging to surgery and improved R1 resection rates documented. This review
documents the current evidence for systemic chemotherapy in adjuvant and neoadjuvant treatment of biliary tract
cancers and highlights the ongoing clinical trials.

Keywords: Cholangiocarcinoma, gallbladder carcinoma, neoadjuvant chemotherapy, adjuvant chemotherapy

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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