Second-line FOLFOX chemotherapy for patients with advanced biliary tract cancers pretreated with cisplatin/gemcitabine: a systematic review and meta-analysis

Abstract

Background: Biliary cancers are aggressive carcinomas frequently diagnosed at an advanced stage. Palliative combination systemic therapy provides survival benefits in the first-line setting of advanced and metastatic disease. FOLFOX chemotherapy is one of the few options in the second-line therapy. Materials and methods: The medical literature was searched through the Medline/PubMed and Embase databases to acquire clinical reports or trials of FOLFOX treatment for biliary cancers in the second-line metastatic setting after first-line cisplatin/gemcitabine chemotherapy. Eligible prospective and retrospective studies were reviewed and included in a meta-analysis with overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) as outcomes of interest. Results: Six clinical studies were eligible and included in the meta-analysis. The ORR with second-line FOLFOX chemotherapy in this population was 10.42% [95% confidence interval (CI) 4.55% to 16.3%]. Two-fifths of the patients had stable disease for a DCR of 50.65% (95% CI 38.4% to 62.9%). The median PFS was 3.03 months (95% CI 1.38-4.09 months) and the median OS was 6.43 months (95% CI 5.43-7.43 months). The main grade 3/4 adverse effects observed in >10% of patients were neutropenia (21.2%) and asthenia/fatigue (10.3%). Conclusions: The meta-analysis observed a moderate efficacy of the FOLFOX combination in this setting. These results may be used as a benchmark to compare gains obtained in this setting with novel treatments, including recently introduced targeted therapies in appropriately selected patients.