Efficacy and safety of goserelin combined with adjuvant chemo- therapy in premenopausal women with breast cancer

This study aims to evaluate the efficacy and safety of goserelin combined with chemotherapy for premenopausal women with breast cancer. Literatures were extracted from databases including Excerpta Medica Database, Springer, Pubmed, China National Knowledge Infrastructure and Chinese Biological Medicine from their inception up to May 2014. The main efficacy measures were 5 years overall survival (OS), 10 years OS, 5 years disease free survival and 5 years progress free survival. Ten randomized comparison clinical trials were eligible in this study. The result showed that goserelin combined with chemotherapy group can improve the survival rate and decrease the incidence of arthralgia in postmenopausal breast cancer patients, respectively, compared to the control group. However, they can increase the occurrence of vomiting during the chemotherapy process. Compared with the simple chemotherapy, goserelin combined with chemotherapy can provide benefits for premenopausal women with breast cancer on improving the survival rate and reducing arthralgia. Article Info Received: 14 July 2015 Accepted: 14 August 2015 Available Online: 27 November 2015 DOI: 10.3329/bjp.v10i4. 24198 Cite this article: Wang Y, Zhu ZF, Pan WJ, Xu Z. Efficacy and safety of goserelin combined with adjuvant chemotherapy in premenopausal women with breast cancer. Bangladesh J Pharmacol. 2015; 10: 988-96. Efficacy and safety of goserelin combined with adjuvant chemotherapy in premenopausal women with breast cancer Yang Wang1, Zheng Fei Zhu1, Wei Jun Pan2 and Zhe Xu1 Department of Pharmacy, Maanshan Municipal Health Hospital For Women And Children, Maanshan, Anhui 243 000, China; Department of Obstetrics, Maanshan Municipal Health Hospital For Women And Children, Maanshan, Anhui 243 000, China. M e ta -a n a ly s is This work is licensed under a Creative Commons Attribution 4.0 License. You are free to copy, distribute and perform the work. You must attribute the work in the manner specified by the author or licensor. Currently, a large number of clinical studies in goserelin have been reported. But there are obvious differences because the size of a single test sample is too small, and interventions and results index adopted in each study are inconsistent. Meta-analysis is applied in this study to comprehensively evaluate the treatment of goserelin combined with chemotherapy for premenopausal women patients, providing more reliable medical evidence for clinical application. Materials and Methods Identification of eligible studies Literatures were extracted from databases including Excerpta Medica Database (EMBASE),Springer, PubMed, China National Knowledge Infrastructure (CNKI) and Chinese Biological Medicine (CBM) from their inception up to May 2014. The search terms were used as follows: ‘Goserelin’, ‘zoladex’, ‘chemotherapy’ and ‘premenopausal women with breast cancer’. Inclusion and exclusion criteria Inclusion criteria include a) randomized clinical trial (RCT); b) premenopausal women with breast cancer; c) the treatment with goserelin combined chemotherapy. Exclusion criteria include a) male breast cancer patients; b) different endpoint or other types of breast diseases; c) patients had previously subjected to chemotherapy, radiotherapy or surgery; d) concurrent infection; e) other malignancy or serious medical illnesses. Data extraction In order to maintain uniformity and reduce potential reporting bias, two independent reviewers extracted data using a standardized collection according to the inclusion and exclusion criteria listed earlier from those databases. The following characteristics were extracted from each study: name of first author, year of publication, location in which the studies were performed, total number of cases and controls, methods of randomization, intervention and treatment duration. If there were discrepancies in all cases, they were discussed between the reviewers before a final consensus was reached. Disagreements were resolved by the third author. Statistical analysis Meta-analysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. The pooled relative ratio (RR) and 95% confidence interval (CI) were used to assess efficacy and safety endpoints. Heterogeneity was analyzed using the I2 statistic: I2 = 100% × (Q-df)/Q. I2 of 0–25% was considered to not have heterogeneity; I2 of 25–50% may represent low heterogeneity; I2 of 50–75% may represent moderate heterogeneity; and I2 of 75–100% indicate high heterogeneity (Ai et al., 2014; Lyu et al., 2014). When no heterogeneity or low heterogeneity was present, the fixed effects model was used for meta-analysis (Chai et al., 2014). When moderate heterogeneity or high heterogeneity was present, the fixed effects model was compared to the random effects model of DerSimonian –Laird (Higgins et al., 2002). Publication bias was assessed using funnel plots with visual inspection of asymmetry. RR, tests for heterogeneity, and forest plots for the relevant comparisons were performed using STATA 12 with Beggr’s bias test and Egger’s bias test, with P ≤ 0.05 indicating potential bias (Yang et al., 2013). Results Eligible studies 1644 publications were initially identified, 1634 studies were excluded, as they were review papers contained no original data, or a reanalysis of data, or measured deferent endpoints, and/or had no control group. Finally, 10 studies (Baum et al., 2006; CastiglioneGertsch et al., 2003; Cheng et al., 2012; Davidson et al., 2005; Gerber et al., 2011; Hackshaw et al., 2009; Karlsson et al., 2011; Kaufmann et al., 2007; Kaufmann et al., 2003; von Minckwitz et al., 2006) with a total sample population of 11171 patients (5433 in the treatment group and 5738 in the control group) were identified based on the inclusion/exclusion criteria (Figure 1). Characteristics of studies included in the current metaanalysis were presented (Table I). Quality assessment All RCTs mentioned random allocation, 8 studies reported and described random allocation methods. None of the studies described the blind method. These RCTs design all include a baseline assessment including patients’ age, stage of disease, etc. No significant differences were found between the baseline data. In these RCTs, three combination chemotherapies have been performed to treat advanced breast cancer: one study used CAF; seven studies used CMF; and the other studies used chemotherapy (Table I). Meta-analysis The main treatment efficacy indicators considered in meta-analysis are: a) 5 years overall survival (OS); b) 10 years OS; c) 5 years disease free survival (DFS); d) 5 years progress free survival (PFS); The indicators for the safety of the treatments are mainly the rate of occurrence of emesis and arthralgia. 5 years OS of patients Ten clinical trials evaluated the 5 years OS of patients. Heterogeneity was considered absent at the I2 statistic (I2 = 2%, p = 0.42). A fixed effects model was performed on outcome measurements. The results show that goserelin combined with chemotherapy could signifiBangladesh J Pharmacol 2015; 10: 988-996 989