Abstract

Background: Advanced cholangiocarcinoma is a rare, aggressive tumor. Treatment is limited and very few systemic therapies are available. An effort for new drugs development is in course, which aims higher response rates, prolonged survival and better quality of life. Currently, immune checkpoint inhibitors and tyrosine kinase inhibitors have been used as new approaches after first- or second-line chemotherapy.

Case Presentation: A 49-year-old woman, diagnosed in 2013 with an intrahepatic cholangiocarcinoma, underwent surgery (pT2pN1) followed by adjuvant capecitabine and radiotherapy. Disease relapse occurred 9 months later, with a unique hepatic lesion that was treated with gemcitabine and cisplatin following liver ablation by radiofrequency. After 2 years, the identification of metastatic lesions in liver, lymph nodes and bones lead the patient to a re-exposure to gemcitabine and cisplatin, which resulted in partial tumor response, accompanied by limiting myelotoxicity induced by chemotherapy. A combination of fluorouracil, leucovorin and irinotecan was started, but disease progressed after 7 cycles. The patient received regorafenib in a third line setting, which resulted in a substantial metabolic response in all secondary lesions. The patient remains with stable disease for more than 16 months.

Conclusion: A surprising prolonged survival with regorafenib was observed. Selecting molecular targets is a promising field in the precision oncology.

Keywords: Advanced cholangiocarcinoma; Regorafenib; Vascular endothelial growth factor inhibitor; Gastrointestinal oncology; Case report

Abbreviations: CG: cisplatin and gemcitabine; CT: chemotherapy; ECOG: Eastern Cooperative Oncology Group; FDG: fluorodeoxyglucose; FGFR1: fibroblast growth factor receptor 1; mFOLFOX: modified fluorouracil, leucovorin and oxaliplatin; GI: gastrointestinal; ICC: intra-hepatic cholangiocarcinoma; IDH: isocitrate dehydrogenase; mIDH1: mutant IDH1; dMMR: DNA mismatch repair deficiency; MSI-H: high microsatellite instability; NGS: next generation sequencing; NTRK: neurotrophic tyrosine receptor kinase; ORR: overall response rate; OS: overall survival; PDGFR-β: platelet-derived growth factor receptor β; PDL1: programmed cell death 1 ligand; PET: positron emission tomography; mPFS: median progression free survival; RT: radiotherapy; TIE2: tyrosine-protein kinase receptor Tie-2; VEGF: vascular endothelial growth factor