Open AccessIncreased Risk of High-Grade Hemorrhage in Cancer Patients Treated with Gemcitabine: A Meta-Analysis of 20 Randomized Controlled Trials
Author(s) -
Yi Hu,
Jingliang Wang,
Haitao Tao,
Bai-Shou Wu,
Jian Sun,
Yao Cheng,
Wei Dong,
Ruixin Li
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0074872
Subject(s) - gemcitabine , medicine , relative risk , incidence (geometry) , randomized controlled trial , meta analysis , lung cancer , subgroup analysis , clinical trial , confidence interval , cancer , oncology , gastroenterology , physics , optics
Purpose Gemcitabine, a third-generation anticancer agent, has been shown to be active in several solid tumors. High-grade hemorrhage (grade≥3) has been reported with this drug, although the overall risk remains unclear. We conducted a meta-analysis of randomized controlled trials evaluating the incidence and risk of high-grade hemorrhage associated with gemcitabine. Methods Pubmed was searched for articles published from January 1, 1990 to December 31, 2012. Eligible studies included prospective randomized controlled phase II and III trials evaluating gemcitabine-based vs non-gemcitabine-based therapy in patients with solid tumors. Data on high-grade hemorrhage were extracted. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of included trials. Results A total of 6433 patients from 20 trials were included. Among patients treated with gemcitabine-based chemotherapy, the overall incidence of high-grade hemorrhage was 1.7% (95%CI: 0.9–3.1%), and the RR of high-grade hemorrhage was 2.727 (95%CI: 1.581–4.702, p<0.001). Exploratory subgroup analysis revealed the highest RR of hemorrhage in non-small-cell lung cancer (NSCLC) patients (RR: 3.234; 95%CI, 1.678–6.233; p <0.001), phase II trials (RR 7.053, 95%CI: 1.591–31.27; p = 0.01), trials reported during 2006–2012 (RR: 3.750; 95%CI: 1.735–8.108, p <0.001) and gemcitabine used as single agent (RR 7.48; 95%CI: 0.78–71.92, p = 0.081). Conclusion Gemcitabine is associated with a significant increase risk of high-grade hemorrhage in patients with solid tumors when compared with non-gemcitabine-based therapy.