Dataset Information

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis.

ABSTRACT:

Purpose

The current meta-analysis aimed to summarize the available evidence for the efficacy and serious adverse events (AEs) associated with use of metronomic chemotherapy (MCT) in patients with metastatic breast cancer (MBC).

Method

Electronic databases (PubMed, EMBASE database, Web of Knowledge, and the Cochrane database) were systematically searched for articles related to the use of MCT in MBC patients. Eligible studies included clinical trials of MBC patients treated with MCT that presented sufficient data related to tumor response, progression-free survival (PFS), overall survival (OS), and grade 3/4 AEs. A meta-analysis was performed using a random effects model.

Results

This meta-analysis consists of 22 clinical trials with 1360 patients. The pooled objective response rate and clinical benefit rate of MCT were 34.1% (95% CI 27.4-41.5) and 55.6% (95% CI 49.2-61.9), respectively. The overall 6-month PFS, 12-month OS, and 24-month OS rates were 56.8% (95% CI 48.3-64.9), 70.3% (95% CI 62.6-76.9), and 40.0% (95% CI 30.6-50.2), respectively. The pooled incidence of grade 3/4 AEs was 29.5% (95% CI 21.1-39.5). There was no statistically significant difference observed in any endpoint between subgroups defined by concomitant anti-cancer therapies or chemotherapy regimens. After excluding one controversial study, we observed a trend showing lower toxicity rates with the use of MCT alone compared to use of MCT with other anti-cancer therapies (P = 0.070).

Conclusions

Metronomic chemotherapy may be effective for use in patients with metastatic breast cancer. MCT used alone is possibly equally effective and less toxic than combination therapies. Well-designed RCTs are needed to obtain more evidence.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5351982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionAcquired resistance to endocrine therapy (ET) remains a big challenge in the management of metastatic breast cancer (MBC). A novel therapeutic agent, histone deacetylase inhibitors (HDACi), targets the abnormal epigenetic modification and may overcome acquired resistance. However, HDACi efficacy and the safety profile for hormone receptor (HoR)-positive/human epidermal growth factor receptor 2 (HER2)-negative MBC remain controversial.MethodsTwo independent reviewers searched PubMed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies on HDACi and HoR+/HER2- MBC. Demographic and clinicopathological parameters were extracted and presented as means and proportions, and between-group differences were assessed by Pearson chi-square test. Fixed- or random-effects models were used for meta-analysis based on inter-study heterogeneity. Pooled results were presented as L'Abbé plot and forest plot. Funnel plot and Egger's test were employed for evaluation of publication bias.ResultsFour studies with 1,457 patients were included for meta-analysis. The overall objective response rates (ORRs) of HDACi + ET (HE) and placebo + ET (PE) groups were 11.52% and 6.67%, respectively. The HE regimen significantly increased ORR (odds ratio [OR] 1.633, 95% confidence interval [CI] = 1.103-2.418, p < 0.05) and showed higher clinical benefit rate (CBR) than the PE regimen (HE vs. PE groups: 38.82% vs. 30.58%, OR 1.378, 95% CI = 1.020-1.861, p < 0.05). Additionally, the HE regimen was associated with prolonged progression-free survival (PFS) (hazard ratio [HR] 0.761, 95% CI = 0.650-0.872, p < 0.001) and overall survival (OS) (HR 0.849, 95% CI = 0.702-0.996, p < 0.001). Regarding safety profile, the HE regimen had increasing toxicity in terms of higher overall adverse event (AE), Grade ≥3 AE, dose modification, and discontinuation rate.ConclusionsThis meta-analysis validated that the HE regimen had superior efficacy over control in terms of ORR, CBR, PFS, and OS, but was accompanied with increasing toxicity. HDACi plus ET could serve as an important option in managing HoR+/HER2- MBC. Future studies may focus on the clinical difference among different HDACi and AE managements to enhance tolerability.