Gemcitabine-based chemotherapy for advanced biliary tract carcinomas

Area of Science:

• Oncology
• Gastroenterology
• Clinical Trials

Background:

• Biliary tract cancers (BTCs) are rare, heterogeneous malignancies including cholangiocarcinomas, gallbladder, and ampullary carcinomas.
• Surgery offers long-term survival for resectable BTCs, but most patients present with advanced or metastatic disease.
• Palliative chemotherapy or supportive care are the main options for unresectable BTCs.

Purpose of the Study:

• To evaluate the benefits and harms of intravenous gemcitabine monotherapy or gemcitabine-based chemotherapy.
• Comparisons include placebo, no intervention, or other non-gemcitabine treatments in adults with advanced BTCs.
• Assessment focuses on mortality, quality of life, tumor progression, and adverse events.

Main Methods:

• Systematic review of randomized clinical trials (RCTs) published up to June 2017.
• Searches conducted across multiple electronic databases (Cochrane, MEDLINE, Embase, etc.) and reference lists.
• Risk of bias assessed using Cochrane methodology; evidence quality rated using GRADE.

Main Results:

• Seven RCTs with 600 participants were included; all had a high risk of bias, yielding very low-certainty evidence.
• Gemcitabine plus cisplatin showed a potential mortality benefit versus S-1 plus cisplatin (RR 0.76, 95% CI 0.58-0.98) but increased thrombocytopenia risk.
• Gemcitabine plus S-1 demonstrated a higher overall response rate versus S-1 alone (RR 2.46, 95% CI 1.27-4.75), with no difference in mortality or serious adverse events.

Conclusions:

• The effects of gemcitabine or gemcitabine-based chemotherapy on mortality and response in advanced BTCs remain uncertain due to very low-certainty evidence.
• Limitations include high risk of bias, insufficient data, imprecision, and potential publication bias.
• Further high-quality randomized clinical trials are essential to establish optimal therapeutic strategies for advanced BTCs.