Biliary tract cancers (BTCs) comprise malignant intrahepatic and extrahepatic cholangiocarcinomas and gallbladder cancers. They are uncommon malignant neoplasms: an estimated 12 360 patients received a diagnosis of extrahepatic cholangiocarcinoma and gallbladder cancer in 2019 in the United States.¹ The exact incidence of intrahepatic cholangiocarcinoma is unknown since it is grouped with primary liver cancer. The prognosis of BTCs is dismal, with a 5-year survival rate of only 10%.² Surgical resection is the only curative modality for localized disease. The treatment of unresectable, recurrent, or metastatic disease remains challenging. Although gemcitabine plus cisplatin has demonstrated significant antitumor activity as first-line therapy for metastatic BTC,³ to our knowledge there is no established systemic therapy after failure of gemcitabine plus cisplatin. In the recent ABC-06 (Advanced Biliary Cancer-06) study, FOLFOX (folinic acid, fluorouracil, and oxaliplatin) was evaluated as second-line treatment after progression when given gemcitabine plus cisplatin, and it demonstrated only a modest 1-month survival benefit vs active symptom control.⁴ Novel effective therapeutic approaches are needed for improvement in the clinical outcomes of patients with BTCs.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis. The incidence of HCC and HCC-related deaths have increased over the last several decades. However, the treatment options for advanced HCC are very limited. Sorafenib remains the only drug approved for systemic treatment for advanced HCC. However, prior to sorafenib era conventional cytotoxic chemotherapies have been studied in advanced HCC. In this review, clinical studies of systemic chemotherapy for advanced HCC will be summarized and discussed.