Treatment of Metastatic Biliary Cancers With Irinotecan and 5-Fluorouracil Based Chemotherapy After Platinum/Gemcitabine Progression: A Systematic Review and Meta-Analysis.

BACKGROUND

Biliary tract carcinomas are cancers that, despite a lower prevalence compared with other gastrointestinal cancers, represent a significant public health burden due to their aggressiveness. The metastatic stage of the disease is highly lethal and difficult to treat. Options of systemic therapies, especially beyond the first line are few and less well established.

METHODS

We performed a systematic review of literature databases to identify studies of the combination of irinotecan and 5-fluorouracil (5-FU) based chemotherapy as treatment of metastatic biliary tract carcinomas in second line, after first line treatment with platinum/gemcitabine chemotherapy. Both prospective and retrospective designs were admissible. A meta-analysis of identified studies to determine summary estimates for overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) was also performed.

RESULTS

The search was performed in PubMed/Medline and in Embase databases and identified a total of 339 articles. Manual review resulted in 8 articles that were eligible for inclusion in the meta-analysis. Second line irinotecan/5-FU based combinations produced an ORR of 9.1% (95% CI, 5.5%-12.6%) and DCR of 43.3% (95% CI, 15.8%-70.8%). Summary PFS and OS were 2.7 months (95% CI, 2.3-3.1 months) and 6.8 months (95% CI, 5.6-8.0 months), respectively. Treatments appeared to be feasible with adverse effect profiles as expected from the combination.

CONCLUSION

A moderate activity of second line irinotecan/5-FU based chemotherapy was observed in this meta-analysis. The combination is an option for patients progressing on platinum/gemcitabine chemotherapy, who maintain a sufficient general status to receive active therapy. This combination may also serve as the control arm of second line trials with new targeted agents.