Cholangiocarcinoma Therapeutics: An Update.

Curr Cancer Drug Targets

Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany.

Published: January 2022

Background: Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer and associated with a poor prognosis. Only one-third of CCA cases are diagnosed at operable stages. However, a high rate of relapse has been observed postoperatively. Besides screening for operable individuals, efficacious therapeutic for recurrent and advanced CCA is urgently needed. The treatment outcome of available therapeutics is important to clarify clinical indication and facilitate the development of treatment strategies.

Objective: This review aims to compare the treatment outcome of different therapeutics based on both overall survival and progression-free survival.

Methods: Over one hundred peer-reviewed articles were examined. We compared the treatment outcome between different treatment methods, including tumor resection with or without postoperative systematic therapy, chemotherapies including FOFLOX, and targeted therapies, such as IDH1, K-RAS, and FGFR inhibitors. Notably, the scientific basis and outcome of available treatment methods were compared with the standard first-line therapy.

Results: CCAs at early stages should firstly undergo tumor resection surgery, followed by postoperative treatment with Capecitabine. Chemotherapy can be considered as a preoperative option for unresectable CCAs. Inoperable CCAs with genetic aberrances like FGFR alterations, IDH1, and KRAS mutations should be considered with targeted therapies. Fluoropyrimidine prodrug (S-1)/Gemcitabine/Cisplatin and nab-Paclitaxel/Gemcitabine/Cisplatin show favorable outcome which hints at the triplet regimen to be superior to Gemcitabine/Cisplatin on CCA. The triplet chemotherapeutic should be tested further compared to Gemcitabine/Cisplatin among CCAs without genetic alterations. Gemcitabine plus S-1 was recently suggested as the convenient and equivalent standard first-line for advanced/recurrent biliary tract cancer.

Conclusion: This review provides a comparative outcome between novel targeted therapies and currently available therapeutics.

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http://dx.doi.org/10.2174/1568009621666210204152028DOI Listing

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