Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis

Cancer Metastasis Rev. 2015 Sep;34(3):429-41. doi: 10.1007/s10555-015-9576-y.


There is a debate whether triplet or doublet chemotherapy should be used as a first-line treatment in patients with advanced or metastatic esophagogastric cancer. Therefore, here we will review the available literature to assess the efficacy and safety of triplet versus doublet chemotherapy as a first-line treatment in patients with advanced esophagogastric cancer. We searched MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) between 1980 and March 2015 for randomized controlled phase II and III trials comparing triplet with doublet chemotherapy and abstracts of major oncology meetings from 1990 to 2014. Twenty-one studies with a total of 3475 participants were included in the meta-analysis for overall survival. An improvement in overall survival (OS) (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.83-0.97) and progression-free survival (PFS) (HR 0.80, 95% CI 0.69-0.93) was observed in favor of triplet. In addition, the use of triplet was associated with better objective response rate (ORR) (risk ratio 1.25, 95% CI 1.09-1.44) compared to doublet. The risks of grade 3-4 thrombocytopenia (6.2 vs 3.8%), infection (10.2 vs 6.4%), and mucositis (9.7 vs 4.7%) were statistically significantly increased with triplet compared to doublet. This review shows that first-line triplet therapy is superior to doublet therapy in patients with advanced esophagogastric cancer. However, the survival benefit is limited and the risks of grade 3-4 thrombocytopenia, infection, and mucositis are increased.

Keywords: Doublet chemotherapy; Esophageal cancer; First-line treatment; Gastric cancer; Palliative chemotherapy; Triplet chemotherapy.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Disease-Free Survival
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / mortality
  • Humans
  • Randomized Controlled Trials as Topic
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality