The Efficacy and Safety of First-line Chemotherapies for Advanced Biliary Tract Cancer: A Network Meta-analysis

Major chemotherapeutic drugs for advanced biliary tract cancer (ABTC) include gemcitabine, fluoropyrimidines and platinum compounds, but the optimum combination of them remains inconclusive. The main objective of this network meta-analysis was to compare the efficacy and safety of first-line chemotherapies for ABTC. Methods: We searched PubMed, EMBASE, the Cochrane library and Science Direct for relevant controlled trials until May 2017. We estimated the Hazard ratios (HRs) for survival time and odds ratios (ORs) for response rate and toxic effects among different therapies. All data were calculated by Aggregate Data Drug Information System (ADDIS) v2.0 online and STATA software. Results: 16 trials involving 2245 patients and 10 regimens were included in this study. In terms of the objective response rate, Cap plus CIS (CapC) exhibited better performance than FU (OR 5.46, 95% CI 1.07-56.63). Gem plus S-1 (GS) was superior to Gem (OR 4.72, 95% CI 1.31-17.02) and FU (OR 9.08, 95% CI 1.56-89.20). Also, GS had an overall survival benefit compared to FU and Gem, with a HR of 0.51 (95% CI 0.28-0.96) and 0.43 (95% CI 0.20-0.93), respectively. Compared with FU, Gem plus OXA (Gemox) prolonged the OS (HR 0.57, 95% CI 0.32-0.96). And FU was also inferior to FP (HR 1.88, 95% CI 1.07-3.16). The PFS did not differ between all regiments. The incidence of grade 3 or 4 hematological toxic effects appeared to be higher in the Gem-based chemotherapies. In regard to nonhematological adverse events, grade 3 or 4 diarrhea and stomotitis occurred more frequently in S-1-based groups. In addition, the Cap plus CIS combination (CapC) were more likely to cause vomiting, stomotitis and hand-foot syndrome. As for peripheral neuropathy, Gem plus OXA (Gemox), CapC and GC were associated with higher risk. There was no difference among different treatments with respect to anorexia, fatigue, nausea, pigmentation, renal dysfunction and asthenia. Conclusion: Physicians should discuss with the patients the different options outlining potential benefit and toxicity since no clear evidence of an approach of choice can be produced.