Efficacy of gemcitabine-based chemotherapy in metastatic breast cancer: a meta-analysis of randomized controlled trials

Objectives: To compare the effects of gemcitabine-based chemotherapy and gemcitabine-free regimens, a metaanalysis of all relevant randomized controlled trials was performed to investigate the improvement in overall response rate (ORR), time to progression (TTP), and overall survival (OS). A subgroup of gemcitabine-based doublet compared with single agent was also analyzed. Methods: The PubMed and Embase databases were searched for relevant publications reporting randomized controlled trials comparing gemcitabine-based chemotherapy and gemcitabine-free regimens between January 1990 and December 2012. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived. Results: Nine trials with a total of 2651 patients were included in this meta-analysis. Compared with gemcitabinefree chemotherapy, gemcitabine-based therapy demonstrated no improvement in terms of ORR (HR 1.09, 95% CI 0.73-1.62; P=0.67), TTP (HR 0.91, 95% CI 0.72-1.15; P=0.44) and OS (HR 1.05, 95% CI 0.88-1.25; P=0.60). In a subgroup including patients who received adjuvant chemotherapy containing anthracyclines or taxanes, sub-analysis assessment revealed that gemcitabine-based doublets were superior to monotherapy in ORR (HR 1.64, 95% CI 1.26-2.12; P=0.0002) and TTP (HR 0.71, 95% CI 0.62-0.81; P<0.00001), but no benefit was observed for OS (HR 0.90, 95% CI 0.79-1.03; P=0.14). The rates of grade 3 and 4 anemia (HR 2.02, 95% CI 1.35-3.02; P=0.006), neutropenia (HR 2.33, 95% CI 1.37-3.63; P=0.01), and thrombocytopenia (HR 8.31, 95% CI 5.00-13.82; P50.0001) were significantly higher in the gemcitabine-based arm. Conclusions: The present study suggests that gemcitabine-based chemotherapy was as effective as gemcitabine-free chemotherapy in patients with metastatic breast cancer with increased hematological toxicity. Subgroup analysis indicated that adding gemcitabine to monotherapy might be more effective.