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

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.

Heterogeneity of first‐line palliative systemic treatment in synchronous metastatic esophagogastric cancer patients: A real‐world evidence study

“…This heterogeneity in treatment is undesirable, especially in case of unconventional treatment combinations, since second-line treatment options are often registered under the assumption that certain compounds have been administered in the first line. 25,26 Since the added value of the addition of an anthracycline to a platinum-fluoropyrimidine doublet remains uncertain, 15,[27][28][29] doublet chemotherapy tends to be the favored choice of firstline palliative treatment because of its better tolerance. Analysis of beyond first-line treatments is currently ongoing.…”

“…[3][4][5][6] However, the optimal first-line palliative systemic therapy regimen for metastatic esophagogastric cancer patients has not yet been identified. 6,14,15 Because of the lack of consensus on optimal palliative systemic treatment, making choices about the best approach for these patients is challenging, which can result in interhospital and interphysician variation in individual systemic treatment. [7][8][9][10][11] Triplet therapy, in which either an anthracycline or taxane is added to the platinum-fluoropyrimidine doublet, is suggested in international guidelines for patients in good condition, 8,10,12,13 but becomes increasingly controversial because of its toxicity.…”

Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells

“…In a large meta-analysis study that included twenty-one studies with a total of 3475 participants, triplet therapy was suggested to be superior to doublet therapy in patients with advanced gastric or esophageal cancer. However, the survival benefit is limited with increased risks for thrombocytopenia, infection, and mucositis (33). Having several factors contribute to development of UGCs and the existence of only few treatment options add extra challenge to our ability to treat them.…”

Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer

“…10.7/5.8 vs. 8.8/3.9 months) [23], or capecitabine and oxaliplatin, OS 8 months [24]. A recent meta-analysis showed a limited survival benefit of triplet chemotherapy with an increased risk of toxicity when compared to doublet chemotherapy [25]. Cisplatin and gemcitabine have a different side effect profile compared with oxaliplatin-based chemotherapy regimens.…”