What is the role of chemotherapy in the management of cholangiocarcinoma (CCC)?

Updated: Dec 28, 2019
  • Author: Peter E Darwin, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Answer

Most often, chemotherapy is given in low doses to act as a radiation sensitizer during a 4- to 5-week course of external-beam radiotherapy. Primary chemotherapy has been evaluated as well, including gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. [33, 34]  However, chemotherapy agents used without radiotherapy or surgery do not appear to provide any local control or meaningful survival benefit.

The most used agent has been 5-fluorouracil, which has a partial response rate of about 12%. Gemcitabine has a similar response rate. Although fluoropyrimidines and doxorubicin have been reported to have response rates as high as 30-40%, partial responses lasting from weeks to months have been observed in only 10-35% of trials. [33, 34] >

A systematic review and meta-analysis found a significant improvement in overall survival with any adjuvant chemotherapy after cholangiocarcinoma surgery compared with surgery only (hazard ratio [HR] 0.74; 95% CI, 0.67 to 0.83; P <  0.001). The benefit of adjuvant therapy extended to patients with margin-positive surgery and node-positive disease. [35]

For patients with intrahepatic cholangiocarcinomas who have no residual local disease after resection, the National Comprehensive Cancer Network (NCCN) suggests observation or adjuvant fluoropyrimidine- or gemcitabine-based chemotherapy. For lesions that are resected with microscopic margins or positive regional nodes, the NCCN recommends fluoropyrimidine chemoradiation or fluoropyrimidine- or gemcitabine-based chemotherapy. No data support aggressive surveillance, but imaging every 6 months for 2 years may be considered, if clinically indicated. [36]

For intrahepatic cholangiocarcinoma with residual local disease after resection, the NCCN's only category 1 recommendation is gemcitabine/cisplatin combination therapy. Locoregional care is a category 2B recommendation, with fluoropyrimidine-based or other gemcitabine-based chemotherapy or best supportive care as other alternatives. [36]

For unresectable extrahepatic cholangiocarcinoma, the NCCN recommends gemcitabine/cisplatin combination therapy (category 1). Alternatives are fluoropyrimidine-based or other gemcitabine-based chemotherapy regimen or fluoropyrimidine chemoradiation. The NCCN also recommends gemcitabine/cisplatin combination therapy as a category 1 option for metastatic extrahepatic cholangiocarcinoma, with fluoropyrimidine-based or other gemcitabine-based chemotherapy regimens as alternatives. [36]


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