Systemic therapy for unresectable, mixed hepatocellularcholangiocarcinoma: Treatment of a rare malignancy

Combined hepatocellular-cholangiocarcinoma (HCC-CC) has a reported incidence of less than 5% of primary hepatic malignancies. The treatment approach to this malignancy is undefined. Our objective of this case series is to provide some insight into chemotherapy and/or targeted therapy in this setting. Methods: Pathologic and radiographic review confirmed seven combined HCC-CC patients during a 5-year time frame [2009-2014]. Data points were demographics, chemotherapy and/or targeted therapy given in the first and second-line setting, localized treatment if given, first radiographic result, progression-free survival (PFS), and overall survival (OS). Results: Seven patients were identified. Front-line treatment showed a median PFS of 3.4 months. Total median OS was 8.3 months. Regimens given included gemcitabine alone +/- bevacizumab, gemcitabine + platinum (GP) +/- bevacizumab, and sorafenib. Front-line treatment with these regimens showed progressive disease in 71% (5 patients) on first radiographic scan with all patients who received sorafenib front-line progressing at that restaging. Disease-control (complete response + partial response + stable disease) was seen in 29% of patients (2 patients) with 1 patient receiving GP and 1 patient receiving gemcitabine + bevacizumab. Of note, 2 patients that received GP +/- bevacizumab in the second-line setting had disease control on first radiographic scan. Conclusions: Our retrospective review speaks to the rarity of this malignancy and challenges that are associated with its diagnosis and treatment. GP +/- bevacizumab showed disease control in first or secondline treatment in 3 patients. Treatment with this regimen in this rare malignancy subgroup warrants further investigation.