Advanced biliary tract cancer: clinical outcomes with ABC-02 regimen and analysis of prognostic factors in a tertiary care center in the United States

Biliary tract cancers (BTC) are diverse malignancies arising from the biliary tract epithelium either intrahepatic or extrahepatic biliary tract. There are about 14,000 new cases per year in the United States (1,2). Most cases of BTC are lethal due to advanced disease at presentation or high relapse rate after local treatment (3-5). Untreated patients with advanced disease have a short survival of 3–4 months (3). Few patients who present with local disease and are potential candidates for surgical resection based on specific radiologic and clinical criteria can be treated surgically (3,6). The outcome of these patients is still dismal with a 5-year survival of 30–40 percent for intrahepatic disease (3). Defining a unified criteria for resectability for BTC is challenging as resectability may differ based on the site of disease: intrahepatic, hilar or extrahepatic cholangiocarcinoma (EHC) (7). Several other factors such as the condition of the patient, expertise of the surgeon and the hospital, and biology are crucial in this decision-making process (7). There is limited data for effective management of advanced unresectable disease. In the absence of standard therapy and randomized phase III clinical trials before 2007, Eckel et al., attempted to identify superior regimen by analyzing available data which consisted of several small and nonrandomized studies (8). This pooled analysis included 112 trial arms and 2,810 patients, and demonstrated that combination chemotherapy with gemcitabine and cisplatin or oxaliplatin increased response rates in advanced BTC’s (8). The first randomized phase II study published in 2007 showed that gemcitabine and cisplatin (GC) had a superior time to progression (8 months) compared to 4 months with Gemcitabine alone (9). Based on the results of the phase II study, the same group conducted a randomized phase III trial comparing GC with gemcitabine alone in which 410 patients were randomized to either of the two groups (4). GC provided an overall survival (OS) advantage over gemcitabine alone in the ABC-02 clinical trial (11.7 vs. 8.1 months) in locally advanced or metastatic intrahepatic cholangiocarcinoma (IHC), EHC, gallbladder cancer (GBC), or ampullary cancer (4). With the exception of neutropenia, both groups had similar adverse events (4)