Disease control with sunitinib in advanced intrahepatic cholangiocarcinoma resistant to gemcitabine-oxaliplatin chemotherapy

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

Figures

Figure 1

Computed tomography scans (A) prior to and (B) 4 mo after initiating sunitinib treatment, demonstrating density variation of three target lesions (arrows) in the liver. Baseline computed tomography (CT) shows heterogeneous lesions with contrast-enhanced peripheral ring, while post-treatment CT shows disappearance of the hypervascular aspect of the three lesions.

Figure 2

Computed tomography scans (A) prior to and (B) 4 mo after initiating sunitinib treatment, showing a partial response according to the response evaluation criteria in solid tumors criteria of a retroperitoneal lymphadenopathy (arrow), and a decrease in tumor density.