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Metronomic Chemotherapy for Metastatic Breast Cancer - a Systematic Review of the Literature.

ABSTRACT: Conventional chemotherapy is generally administered in high doses followed by a treatment-free period to give the body needful time to recover. This "maximum tolerated dose" approach results in high response rates. However, long periods between therapy cycles can lead to development of resistance mechanisms and consequently disease progression. One of the most interesting alternative strategies is metronomic chemotherapy. This concept relies on the continuous administration of chemotherapy at low doses and aims at targeting endothelial cells in the tumor bed as well. Recently, metronomic chemotherapy has been incorporated into the recommendations issued by the German AGO expert panel (www.ago-online.de). A systematic review of PubMed/Medline, ClinicalTrials.gov, the European Clinical Trials Database (EudraCT) and the Cochrane Database was conducted. In the present review, we discuss the current evidence on metronomic chemotherapy in metastatic breast cancer.

SUBMITTER: Banys-Paluchowski M

PROVIDER: S-EPMC4873299 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Metronomic Chemotherapy for Metastatic Breast Cancer - a Systematic Review of the Literature.

Banys-Paluchowski M M Schütz F F Ruckhäberle E E Krawczyk N N Fehm T T

Geburtshilfe und Frauenheilkunde 20160501 5

Conventional chemotherapy is generally administered in high doses followed by a treatment-free period to give the body needful time to recover. This "maximum tolerated dose" approach results in high response rates. However, long periods between therapy cycles can lead to development of resistance mechanisms and consequently disease progression. One of the most interesting alternative strategies is metronomic chemotherapy. This concept relies on the continuous administration of chemotherapy at lo ...[more]

PMID: 27239061

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Project description:BackgroundAlthough various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC), the safety and efficacy of nab-paclitaxel remain unclear which need to be systematically evaluated.MethodsElectronic searches for prospective clinical trials evaluating nab-paclitaxel monotherapy for MBC were performed. Requisite data were extracted, integrated and analysed from the included studies according to the different study designs using systematic review and meta-analysis. Meta-regression and subgroup analysis were further performed to explore the potential risk factors affecting each individual outcome of interest following nab-paclitaxel monotherapy.ResultsTwenty-two studies with 3287 MBC patients were included. A total of 1685 MBC patients received nab-paclitaxel as first-line therapy, 640 patients as further-line therapy, and 962 patients as mixed-line therapy. A total of 1966 MBC patients (60.40%) received nab-paclitaxel weekly, 1190 patients (36.56%) received nab-paclitaxel triweekly and 99 patients (3.04%) received nab-paclitaxel biweekly. The overall incidence rates of all-grade neutropenia, leukopenia, peripheral sensory neuropathy, and fatigue were 52% (95% CI, 38-66%, I2 = 98.97%), 58% (95% CI, 43-73%, I2 = 97.72%), 58% (95% CI, 48-68%, I2 = 97.17%), and 49% (95% CI, 41-56%, I2 = 94.39%), respectively. The overall response rate (ORR) was 40% (95% CI, 35-45%, I2 = 98.97%), and the clinical benefit rate (CBR) was 66% (95% CI, 59-73%, I2 = 98.97%) following nab-paclitaxel monotherapy. The median progression-free survival (PFS) was 7.64 months (95% CI, 6.89-8.40 months, I2 = 92.3%), and the median overall survival (OS) was 24.51 months (95% CI, 21.25-27.78 months, I2 = 92.7%). Treatment line, human epidermal growth factor receptor-2(Her-2)-negative status and dosage were found to be sources of heterogeneity among the included studies. According to the meta-regression and subgroup analysis, grade 3/4 neutropenia occurred less frequently in Her-2-negative patients than in the entire population (P = 0.046). Patients who received first-line nab-paclitaxel monotherapy showed a higher ORR (P = 0.006) and longer PFS (P = 0.045). Efficacy outcomes were not affected by the administration schedule. However, within the same schedule, patients appeared to have a superior ORR (P = 0.044) and longer PFS (P = 0.03) with an increasing dosage of nab-paclitaxel administered.ConclusionsThe benefits brought by nab-paclitaxel mono-chemotherapy in the treatment of MBC are considerable while the harm is generally manageable. Further study and validation are needed to figure out the roles which the dosage, schedule and other factors play actually in nab-paclitaxel chemotherapy.

Dataset Information

Metronomic Chemotherapy for Metastatic Breast Cancer - a Systematic Review of the Literature.

Publications

Metronomic Chemotherapy for Metastatic Breast Cancer - a Systematic Review of the Literature.

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