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Review
. 2015 Jul;47(3):343-61.
doi: 10.4143/crt.2014.308. Epub 2015 May 18.

Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer: A Systematic Review

Joon Oh Park  1 , Do-Youn Oh  2 , Chiun Hsu  3 , Jen-Shi Chen  4 , Li-Tzong Chen  5 , Mauro Orlando  6 , Jong Seok Kim  7 , Ho Yeong Lim  1
Affiliations
Review

Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer: A Systematic Review

Joon Oh Park et al. Cancer Res Treat. 2015 Jul.

Abstract

Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin.

Keywords: Biliary tract neoplasms; Cholangiocarcinoma; Cisplatin; Gallbladder neoplasms; Gemcitabine.

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Conflict of interest statement

Eli Lilly and Company, manufacturer/licensee of gemicitabine (Gemzar), was involved in the study design, data collection, data analysis, and preparation of the manuscript. Do-Youn Oh has received research funding from Eli Lilly. Jen-Shi Chen has received consultancy fees and honoraria from Eli Lilly, Roche, and Novartis. Li-Tzong Chen has received honoraria from Eli Lilly, Novartis, TTY Biopharm, and PharmaEngine, and support for investigator-initiated trials from Merck Serono, Novartis, Sanofi-Aventis, and TTY. Jong Seok Kim is an employee of and owns stock in Eli Lilly Korea Ltd., Republic of Korea. Mauro Orlando is an employee of and owns stock in Eli Lilly Interamerica, Argentina. Joon Oh Park, Chiun Hsu, and Ho Yeong Lim have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Publication flow diagram. ASCO, American Society of Clinical Oncology; BTC, biliary tract cancer; ECCO, European CanCer Organisation; ESMO, European Society for Medical Oncology; gem/cis, gemcitabine-cisplatin therapy; GI, gastrointestinal.
Fig. 2.
Fig. 2.
Forest plots of median overall survival (A) and overall response rate (B) reported in individual publications of prospective studies. Error bars represent 95% confidence intervals (CI; where reported). The number of participants treated with gemcitabine-cisplatin in each study is shown in parentheses.
Fig. 3.
Fig. 3.
Forest plots of median overall survival and response rate plotted against the percentage of participants with gallbladder cancer (A) and metastatic disease (B) reported in individual publications of prospective studies. Error bars represent 95% confidence intervals (CI; where reported).
Fig. 4.
Fig. 4.
Forest plots of median overall survival and response rate in individual publications of prospective studies, grouped by geographic region (Western countries vs. Asian countries). Error bars represent 95% confidence intervals (CI; where reported).
Fig. 5.
Fig. 5.
Incidence of hematologic toxicities in individual publications according to gemcitabine dose (A) and frequency of cisplatin (B).
See this image and copyright information in PMC

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