Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma

Abstract

We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log‐rank test determined the significance of each prognostic factor. Elevated alpha‐fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19‐9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First‐line chemotherapy included platinum‐containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression‐free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child‐Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum‐containing regimens (HR: 15.83 [95% CI: 2.25‐111.43], P = .006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second‐line therapy. In conclusion, the platinum‐containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma

“…This was partially because the pattern of tumor markers and the imaging ndings of cHCC-CCA recurrence resemble those of HCC. Due to the small number of the cHCC-CCA cases, the optimal treatment for cHCC-CCA recurrence remains unclear [18][19][20]. However, to our knowledge, this report is the rst to describe the characteristics of cHCC-CCA recurrence in detail [12,21].…”

Treatment of Combined Hepatocellular and Cholangiocarcinoma

“…In a stark contrast with surgery, the role of systemic chemotherapy in HCC-CC remains unclear. Due to the rarity of this tumour, a standard of treatment has not been established, and current evidence relies on case reports and small retrospective studies in which patients were treated according to the guidelines of either HCC or CC [60,61].…”

“…Another retrospective study evaluated 36 patients with advanced HCC-CC treated with systemic chemotherapy. The first line treatment included GEM+CDDP (n = 12), gemcitabine plus 5-fluorouracil (GEM+5-FU, n = 11), sorafenib (n = 5), and other regimes (n = 8, including S-1 monotherapy, gemcitabine monotherapy, and gemcitabine plus S-1) [61]. The median OS of GEM+CDDP, GEM+5-FU, sorafenib, and other groups was 11.9, 10.2, 3.5, and 8.1 months, respectively.…”

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

“…More recently there has been positive data in first line treatment setting for HCC patients using immune checkpoint inhibitor (ICPI) therapies in combination with other agents such as bevacizumab, or tyrosine kinase inhibitors such as lenvatinib which has led to approval by the Food and Drug Administration (FDA) in the United States of America (89,90). Evidence for utility of TKIs in cHCC-ICC patients is generally in the form of case-reports and single-center retrospective studies with a very weak signal of efficacy, but in the absence of international guidance and concerns about toxicity of cytotoxic chemotherapy they are commonly offered to patients (77,(91)(92)(93).…”

“…The comparative data on systemic therapy in cHCC-ICC is sparse, but tends to favor the efficacy of chemotherapy over sorafenib (77,92,93). In small retrospective studies (n = 41, 28 and 17), cytotoxic regimens seem to achieve a reasonable response rate and modest mOS benefit (77,92,93).…”