Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy

Background: Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear survival advantage over gemcitabine alone and has become a new standard in advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX) combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have shown efficacy in phase II trials and there is no comparative study between different platinum salts. We assessed the efficacy and safety of different platinum-based chemotherapies at first line in aBTC patients. We also analysed the second-line chemotherapy. Methods: Sixty-four consecutive patients with aBTC diagnosed between 1998 and 2010 were included for analysis. At first line chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m(2) and oxaliplatin 100 mg/m(2) Day 1, every 2 weeks), and 20 patients received Gem/Carb regimen (gemcitabine at 1000 mg/m(2) Days 1 and 8 with carboplatin delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks). At second line, a total of 16 patients received a fluoropyrimidine-based chemotherapy. Results: With GEMOX regimen, median progression-free survival (PFS) was 3.7 months (95% CI, 2.4 to 5) and median overall survival (OS) was 10.5 months (95% CI, 6.4 to 14.7). The main toxicity was peripheral neuropathy (20% grade 2 and 7% grade 3). Grade 3/4 haematological toxicities were rare. With Gem/Carb regimen, PFS was 2.5 months (95% CI, 2.1 to 3.7) and OS was 4.8 months (95% CI, 3.7 to 5.8). The main grade 3/4 toxicities were haematological: anaemia (45%), thrombocytopenia (45%), and neutropenia (40%). At second-line, fluoropyrimidine-based chemotherapy was feasible in only a fourth of the patients. The median OS was 5.3 months (95% CI, 4.1 to 6.6), and median PFS was 4.0 months (95% CI, 2.6 to 5.5). Conclusions: One day GEMOX regimen has a favourable toxicity profile and could be an alternative to standard Gem/CDDP regimen, in particular in unfit patients for CDDP. At second-line, selective patients may benefit from fluoropyrimidine-based chemotherapy.