No standard second-line chemotherapy regimen has been established for gemcitabine (GEM)-refractory advanced biliary tract cancer (aBTC).
We examined the transition rate to second-line chemotherapy and its safety and efficacy in patients with aBTC who had received first-line treatment with GEM-based chemotherapy between January 2009 and December 2015 in our hospital. We also investigated prognostic factors associated with overall survival (OS) by multivariable Cox regression analysis.
Forty-six (45.1%) patients received second-line chemotherapy. One patient was excluded from this study, because second-line treatment was initiated in another hospital. The median age was 68 years, and there were 25 males and 20 females. Tumor sites were: gallbladder (n = 18), extrahepatic (n = 15), intrahepatic (n = 10) bile duct and ampulla of Vater (n = 2). Performance status was 0 and 1 in 25 and 20 patients, respectively. Cancer was metastatic in 27, recurrent in 15, and locally advanced in 3. Median CA 19-9 value was 487 U/mL. Modified Glasgow prognostic score (mGPS) were: 0 (n = 24), 1 (n = 10), and 2 (n = 10). First-line chemotherapy were included: GEM + cisplatin (CDDP) (n = 19), GEM + S-1 (n = 14), GEM (n = 7), GEM + OTS102 (n = 4), and GEM + radiation (n = 1). Second-line chemotherapy included: S-1 (n = 20), GEM + oxaliplatin (n = 6), GEM + CDDP (n = 5), GEM (n = 5), tyrosine kinase inhibitors (n = 5), GEM + S-1 (n = 2), and fixed-dose GEM + S-1 (n = 2). The main grade 3/4 adverse events were biliary tract infection (n = 6), neutropenia (n = 5), and anemia (n = 5). There was one treatment-related death due to biliary tract infection. Median OS was 8.3 months, and median progression-free survival was 3.0 months. Response rate was 0% and disease control rate was 58.1%. Multivariate analysis showed that CA 19-9 ≥500 U/mL (hazard ratio: [HR] 3.45, p = 0.003), mGPS ≥1 (HR 3.05, p = 0.005), and liver metastasis (HR 2.62, p = 0.048) were significant prognostic factors for OS.
Second-line chemotherapy for GEM-refractory aBTC was inadequate. Randomized controlled trials with an appropriate stratification criteria, including CA 19-9 value, mGPS and liver metastasis, are required.
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Legal entity responsible for the study
J. Furuse: Personal financial interests from Taiho Pharmaceutical Co., Ltd, and Eli Lilly Japan. Institutional financial interests from Taiho Pharmaceutical Co., Ltd.
All other authors have declared no conflicts of interest.