Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer: A meta-analysis

Abstract

AIM:To investigate the efficacy and safety of gemcitabine (Gem)-based combination chemotherapies for the treatment of advanced biliary tract cancer. METHODS:Clinical trials were identified by searching scientific literature databases (PubMed, EMBASE and the Cochrane Library) for studies published between 1975 and 2013. Two reviewers independently evaluated the relevant studies and manually searched references from these reports to locate additional eligible studies. The disease response and control rates, progressionfree and overall survivals, and the grade 3-4 toxicities were evaluated by a meta-analysis. Odds-ratios (ORs) of the disease response and control rates and grade 3-4 toxicities, and the mean difference (MD) of both progression-free and overall survivals were calculated and used for statistical analysis. RESULTS:Seven randomized trials with a total of 858 patients were selected and included in the final analysis. The studies were divided into subgroups based on the chemotherapy regimens, including Gem-based and non-Gem-based chemotherapies. The overall analyses revealed that the patients treated with Gem-based combination chemotherapy had significantly higher disease response rates [OR = 1.69, 95% confidence interval (CI): 1.17-2.43; P = 0.01], a longer progressionfree survival (MD = 1.95, 95%CI: 0.90-3.00; P = 0.00) and a longer overall survival (MD = 1.85, 95%CI: 0.26-3.44; P = 0.02). A higher incidence of grade 3-4 hematological toxicities, including leukopenia (OR = 2.98, 95%CI: 1.44-6.20; P = 0.00), anemia (OR = 2.96, 95%CI: 1.79-4.92; P = 0.00) and neutropenia (OR = 2.80, 95%CI: 1.39-5.64; P = 0.00) was found in the Gem-based combination chemotherapy group compared with the Gem monotherapy and non-Gem-based chemotherapy groups. CONCLUSION:Gem-based combination chemotherapy is a potential first-line treatment for advanced biliary tract cancer as a result of improved survival, though with additional toxicity.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Biliary tract cancer; Combination chemotherapy; Gemcitabine; Meta-analysis; Randomized trial Core tip: To investigate the efficacy and safety of gemcitabine (Gem)-based combination chemotherapy for the treatment of advanced biliary tract cancer, the authors analyzed the potential impact of Gem-based combination chemotherapy and other regimens on the outcomes and toxicities of the patients using metaanalysis methodologies. Meta-analysis showed that compared with Gem monotherapy and non-Gem-based chemotherapy, Gem-based combination chemotherapy provided a modest improvement in survival but was associated with more toxicity. META-ANALYSIS

EGFR Target Therapy Combined with Gemox for Advanced Biliary Tract Cancers: a Meta-analysis based on RCTs

“…Eckel F. presented a pooled analysis of 104 trials containing 2810 evaluable patients with advanced BTCs and showed that the response rates and tumour control rates were higher for the patient subgroup receiving a combination of gemcitabine and platinum-based agents 30 . Tian-Tian Sun and Heng Liu performed a meta-analysis and systematic review in 2013 and 2014 31 , 32 and reported the efficacy and safety of gemcitabine and platinum-based chemotherapy compared with gemcitabine alone. However, many clinical trials have conflicting outcomes.…”

The potential of radiolabeled chemotherapeutics in tumor diagnosis: Preliminary investigations with 68Ga‐gemcitabine

“…By virtue of its distinctive features of cellular pharmacology, metabolic properties, and mechanistic characteristics, gemcitabine occupies an important place at the forefront of chemotherapy for the treatment of a wide variety of tumors (Ciccolini, Serdjebi, Peters, & Giovannetti, 2016;Crin o & Cappuzzo, 2002;Dubey, Saneja, Gupta, & Gupta, 2016;Ducoulombier, Cousin, Kotecki, & Penel, 2016;Hansen, 2001;Liu, Zhang, Li, Zhang, & Lu, 2014;Ottaiano et al, 2017;Rizzuto, Ghazaly, & Peters, 2017;Schlack, Boegemann, Steinestel, Schrader, & Krabbe, 2016;Thigpen, 2002;Zhang et al, 2017;Zhao, Guo, Sun, Lv, & Qiu, 2017). The source of cytotoxic activity of gemcitabine is primarily attributed to its ability to transport across the cell membrane to get phosphorylated efficiently, slower rate of elimination along with selfpotentiation mechanisms to mask DNA chain termination and extensive inhibitory efficiency against several enzymes (Barton- Burke, 1999;Plunkett et al, 1995;Plunkett, Huang, Searcy, & Gandhi, 1996;Plunkett, Huang, & Gandhi, 1997).…”

Chemotherapy and targeted therapy for advanced biliary tract cancers：An umbrella review

“…Two literatures reported the efficacy and safety comparison of gemcitabine-based combination chemotherapy and gemcitabine monotherapy [22,24] (Table 2). Lawrence Chen's meta-analysis showed [22] that combination chemotherapy was superior to single drug chemotherapy in terms of OS(WMD=-3.52,95%CI -5.14-1.35; HR = 0.65, 95% CI 0.53-0.79),PFS(WMD = 2.60, 95% CI 3.81-1.40; HR=0.63,95%CI 0.52-0.76) and ORR(OR=0.53,95%CI 0.31-0.88).…”

“…Lawrence Chen's meta-analysis showed [22] that combination chemotherapy was superior to single drug chemotherapy in terms of OS(WMD=-3.52,95%CI -5.14-1.35; HR = 0.65, 95% CI 0.53-0.79),PFS(WMD = 2.60, 95% CI 3.81-1.40; HR=0.63,95%CI 0.52-0.76) and ORR(OR=0.53,95%CI 0.31-0.88). In addition, among the toxic reactions reported [24] , lymphocytopenia (OR=1.82,95%CI 1.13-2.94), anemia (OR=1.96,95%CI 1.07-3.62) and neutropenia(OR=1.78,95%CI 1.19-2.66) were higher in the combined chemotherapy group than in the single chemotherapy group, while thrombocytopenia (OR=1.13,95%CI 0.60-2.14) and increased ALT levels (OR=0.76,95%CI 0.47-1.25) were not different between groups.…”