Overall survival benefits for irinotecan‐containing regimens as first‐line treatment for advanced gastric cancer: An updated meta‐analysis of ten randomized controlled trials

Abstract

The standard treatment for patients with advanced gastric cancer (AGC) is still debated, and the available data on the benefit of irinotecan-containing regimen as first-line treatment for those patients are controversial. We performed a systematic review and meta-analysis of randomized controlled trials to determine the survival benefits of irinotecan-containing regimens in this setting. A total of 1,837 patients from ten trials were included in the analysis. Our results showed that irinotecan-containing regimens significantly improved overall survival [OS: hazard ratio ( Gastric cancer is the fourth most frequent malignant disease and the second most common cause of cancer-related deaths worldwide. A total of 989,600 new gastric cancer cases and 738,000 deaths are estimated to have occurred in 2008, accounting for 8% of the total cases and 10% of total cancerrelated deaths, respectively.1-3 Although the overall incidence of gastric cancer in the Western countries, Japan, Korea and China has decreased, the incidence of proximal gastric cancer has increased. 4 Moreover, the decline in gastric cancer incidence in China has been slower than in the Western countries, Japan and Korea and will be offset by population growth and aging.5 As a result, gastric cancer remains an important public health burden in the world.As for early and locally advanced gastric cancer (AGC), surgery remains the mainstay of curative treatment; however, relapse is common, and the majority of patients present with advanced disease. Although systemic chemotherapy has a proven palliative role in patients with AGC, significantly improving quality of life and prolonging survival compared to best supportive care alone 6 ; the prognosis of patients in this setting remains dismal with overall 5-year survival rate ranging from 10 to 15% in the Western countries, Japan and Korea.7 During the past decades, a large number of chemotherapy regimens including 5-fluorouracil (5-FU) and cisplatin (CF), epirubicin, cisplatin and infused 5-FU (ECF) or docetaxel, cisplatin and 5-FU (DCF) regimens have been tested in clinical studies 6,[8][9][10][11][12][13] ; however, the additional survival advantage yielded by these combination therapies appears to be marginal. As a result, there is still no internationally accepted standard of care, and uncertainty remains regarding the choice of the regimen. Obviously, it is necessary to develop new active agents and combination regimens to achieve greater survival benefits in AGC.Irinotecan is a semisynthetic, water-soluble derivative of the plant alkaloid camptothecin. Following conversion to its active metabolite, SN-38, irinotecan acts by inhibiting DNA topoisomerase-I, thereby interfering with DNA replication and cell division. 14,15 In early phase trials in AGC, singleagent irinotecan administered every 2, 3 or 4 weeks demonstrates efficacy in both first-and second-line treatment settings with response rates of 18-23% 16-18 and 43.9-48% when combined with cisplatin. 19,20 Moreover, two published metaanalyses compari...

Management of advanced gastric cancer: An overview of major findings from meta-analysis

“…Additionally, statistically similar overall RR was observed in two meta-analyses [51, 52]. Another one found similar objective RR between two groups [35]. One meta-analysis did not report relevant data.…”

“…When it comes to OS, three of them demonstrated that the survival was statistically similar [51, 52, 59] while one meta-analysis favored CPT-11-containing therapy in terms of OS but the 1-year survival rate did not show significant difference between two groups [35]. Additionally, statistically similar overall RR was observed in two meta-analyses [51, 52].…”

“…The efficacy of CPT-11-based therapy versus non-CPT-11-based therapy was summarized in four meta-analyses [35, 51, 52, 59]. When it comes to OS, three of them demonstrated that the survival was statistically similar [51, 52, 59] while one meta-analysis favored CPT-11-containing therapy in terms of OS but the 1-year survival rate did not show significant difference between two groups [35].…”

“…One meta-analysis did not report relevant data. Two meta-analyses reported PFS [35, 51]. One favored CPT-11-containing regimen [35] while the other showed no significant difference between two groups [51].…”

“…Two meta-analyses reported PFS [35, 51]. One favored CPT-11-containing regimen [35] while the other showed no significant difference between two groups [51]. Besides, one meta-analysis reported TTF, which indicated that CPT-11-based therapy was favorable regarding TTF [52].…”