Case Report
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 28, 2015; 7(6): 910-915
Published online Apr 28, 2015. doi: 10.4254/wjh.v7.i6.910
Disease control with sunitinib in advanced intrahepatic cholangiocarcinoma resistant to gemcitabine-oxaliplatin chemotherapy
Chantal Dreyer, Marie-Paule Sablin, Mohamed Bouattour, Cindy Neuzillet, Maxime Ronot, Safi Dokmak, Jacques Belghiti, Nathalie Guedj, Valérie Paradis, Eric Raymond, Sandrine Faivre
Chantal Dreyer, Marie-Paule Sablin, Mohamed Bouattour, Cindy Neuzillet, Eric Raymond, Sandrine Faivre, Department of Medical Oncology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 92110 Clichy, France
Mohamed Bouattour, Department of Hepatology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 92110 Clichy, France
Maxime Ronot, Department of Imaging, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 92110 Clichy, France
Safi Dokmak, Jacques Belghiti, Department of Biliary and Pancreatic Surgery, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 92110 Clichy, France
Nathalie Guedj, Valérie Paradis, Department of Pathology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 92110 Clichy, France
Author contributions: Dreyer C, Belghiti J, Raymond E and Faivre S conceived and designed the study; Dreyer C, Dokmak S, Belghiti J, Guedj N, Paradis V and Faivre S provided study materials of patients; Dreyer C, Sablin MP, Bouattour M and Faivre S collected and assembled data; Dreyer C, Sablin MP, Bouattour M, Raymond E and Faivre S analyzed and interpreted data; Ronot M and Faivre S participated in the acquisition and interpretation of radiological figures; all authors participated in manuscript written; all authors give final approval of manuscript.
Supported by Pfizer Inc, funding ACUMED (Tytherington, UK) for manuscript editing.
Ethics approval: The Ethics approval is not mandatory in France for individual compassionate use of a drug that has been approved in another indication.
Informed consent: An individual consent has been obtained from each patient regarding the off-label use of sunitinib in cholangiocarcinoma.
Conflict-of-interest: Eric Raymond and Sandrine Faivre have received honoraria from Pfizer. All other authors have no disclosures to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Mohamed Bouattour, Department of Medical Oncology and Hepatology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110 Clichy, France. mohamed.bouattour@bjn.aphp.fr
Telephone: +33-1-40875525 Fax: +33-1-40875487
Received: September 2, 2014
Peer-review started: September 2, 2014
First decision: November 27, 2014
Revised: January 10, 2015
Accepted: February 9, 2015
Article in press: February 11, 2015
Published online: April 28, 2015
Abstract

Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment (Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy may be associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase II multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma (SUN-CK study; NCT01718327).

Keywords: Biliary tract tumors, Antiangiogenic therapy, Hypodensity, Tumor response, Vascular endothelial growth factor receptor inhibitors, Chemoresistance

Core tip: No systemic therapy after progression on platinum-based chemotherapy is currently approved. Based on imaging hypervascular pattern and molecular expression of vascular endothelial growth factor, we evaluated sunitinib, a multikinase inhibitor as second line treatment in patients with advanced intrahepatic cholangiocarcinoma. We report 3 cases of disease control lasting 4-16 mo that provide the rational for developing prospective clinical trials with sunitinib in second line for advanced intrahepatic cholangiocarcinoma.