Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10555-015-9576-y) contains supplementary material, which is available to authorized users.
Highlights
Gastric and esophageal cancers are respectively the second and the sixth most common cause of cancer-related deaths worldwide
Guidelines of 2013 state that Bcombination regimens incorporating a platinum agent and a fluoropyrimidine are generally used. It remains controversial whether a triplet regimen is needed [8].^ In recently published randomized trials introducing targeted therapies in first-line treatment, mainly doublets have been used as the backbone chemotherapy [9,10,11], one trial used a triplet [12]
Our systematic review and meta-analysis showed that a triplet regimen was superior to a doublet regimen in terms of overall survival, progression-free survival, and objective response rate
Summary
Gastric and esophageal cancers are respectively the second and the sixth most common cause of cancer-related deaths worldwide. The majority of patients presents with advanced disease or develops metastases after treatment with curative intent. In these patients, palliative systemic chemotherapy improves survival and quality of life, compared to best supportive care [1,2,3]. Guidelines of 2013 state that Bcombination regimens incorporating a platinum agent and a fluoropyrimidine are generally used It remains controversial whether a triplet regimen is needed [8].^ In recently published randomized trials introducing targeted therapies in first-line treatment, mainly doublets have been used as the backbone chemotherapy [9,10,11], one trial used a triplet [12]. Here we will systematically review the existing literature on triplet or doublet therapy in terms of overall survival, progression-free survival, objective response rate, and safety in the management of advanced esophagogastric cancer
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