A phase II trial of biweekly vinorelbine and oxaliplatin in second- or third-line metastatic triple-negative breast cancer

2016

Oncology Reports

As a main active compound in the bark of waxberry (Myrica rubra), myricetin is a macrocyclic diarylheptanoid, and can trigger the apoptosis of HeLa and PC3 cells. The aim of the present study was to elucidate the anticancer effect of myricetin on human breast cancer MCF-7 cells and to explore the possible mechanisms of action. MCF-7 cells were treated with different concentrations of myricetin (0-80 µM) for 12, 24 and 48 h. In the present study, we found that myricetin suppressed the cell viability of the MCF-7 cells at least partly through the induction of apoptosis as determined by MTT assay and flow cytometry. Western blot analysis revealed that myricetin effectively suppressed the protein expression of p21-activated kinase 1 (PAK1), MEK and phosphorylated extracellular mitogen-activated protein kinase (ERK1/2). In addition, treatment of myricetin activated glycogen synthase kinase-3β (GSK3β) and Bax protein expression, and inhibited β-catenin/cyclin D1/proliferating cell nuclear antigen (PCNA)/survivin and promoted caspase-3 activity in the MCF-7 cells. These results demonstrated that myricetin suppressed the cell viability of human breast cancer MCF-7 cells through PAK1/MEK/ERK/GSK3β/β-catenin/cyclin D1/PCNA/survivin/Bax-caspase-3 signaling.

Section: Discussionmentioning

confidence: 61%

Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway

Jiao

2016

Oncology Reports

“…While previous cohort studies [20][21][22], retrospective observations [23][24][25][26], and case reports [27,28] have addressed the clinical treatment of TNBC with apatinib or vinorelbine (Table 1), a randomized controlled clinical trial has not been reported in North China. As BRCA-positive patients would have poor responses to the therapeutic methods designed in this study, BRCA-negative female patients with locally recurrent or metastatic TNBC, who have previously received anthracycline and taxane treatment, will be the target population in this trial.…”

Section: Study Features and Objectivesmentioning

confidence: 99%

Combined use of apatinib mesylate and vinorelbine versus vinorelbine alone in recurrent or metastatic triple-negative breast cancer: study protocol for a randomized controlled clinical trial

et al. 2020

Preprint

Background: The emergence of new molecular targeted drugs provides new prospects for the treatment of advanced breast cancer; the future therapeutic trend includes chemotherapy combined with molecular targeted therapy. Apatinib mesylate, a novel, small anti-angiogenic agent, highly selectively inhibits the activity of vascular endothelial growth factor receptor-2 tyrosine kinase. Apatinib mesylate also blocks the signaling of vascular endothelial growth factor binding to its receptor, thereby strongly inhibiting tumor angiogenesis and exerting an anti-tumor effect. However, a randomized controlled clinical trial of apatinib combined with vinorelbine for triple-negative breast cancer (TNBC) has not been reported. We will compare the therapeutic effect of vinorelbine alone, or in combination with apatinib mesylate, in patients with recurrent or metastatic TNBC in North China who have received at least two drug treatments, including anthracyclines and taxanes. Methods/analysis: This study is a triple-blind, randomized, placebo-controlled, parallel-group clinical trial. We plan to include 210 female patients with locally recurrent or metastatic TNBC, admitted at the Liaoning Cancer Hospital & Institute, Northeast China. All enrolled patients will be randomized to oral vinorelbine alone (40 mg, thrice a week [Mondays, Wednesdays, and Fridays] in each 3-week cycle), or in combination with oral apatinib mesylate (500 mg, once daily in each 3-week cycle). Radiographic assessment will be performed every 6 weeks for 36 weeks, and every 9 weeks thereafter. The primary outcome is progression-free survival, and secondary outcomes include overall survival, disease control rate, objective response rate, and incidence of adverse events at grades 3 and 4, as defined by the National Cancer Institute Common Toxicity Criteria Version 4.0. Outcome measures will be evaluated at baseline (< 2 weeks before starting treatment), every 6 weeks during treatment, and at 4 weeks and every 3 months after treatment discontinuation. Discussion: Based on the data from this trial, we hope to identify a treatment plan that is suitable for female TNBC patients in Northeast China who have been treated with anthracyclines and taxanes. Trial registration: ClinicalTrials.gov (identifier: NCT03932526). Registered on April 30, 2019.

“…Currently, there are cohort studies [16][17][18], retrospective observations [19][20][21][22] and case reports [23,24] addressing the clinical treatment of TNBC with apatinib or vinorelbine ( Table 1). However, a randomized controlled clinical trial of apatinib combined with vinorelbine for TNBC has not been reported.…”

Section: Study Features and Objectivesmentioning

confidence: 99%

Combined use of apatinib mesylate and vinorelbine versus single use of vinorelbine in recurrent or metastatic triple-negative breast cancer: study protocol for a randomized controlled clinical trial

et al. 2019

Preprint

Background: The emergence of new molecular targeted drugs provides new prospects for the treatment of advanced breast cancer; the future therapeutic trend includes chemotherapy combined with molecular targeted therapy. Apatinib mesylate, a novel small anti-angiogenic agent, highly selectively inhibits the activity of vascular endothelial growth factor receptor-2 tyrosine kinase. Apatinib mesylate also blocks the signaling of vascular endothelial growth factor binding to its receptor, thereby, strongly inhibiting tumor angiogenesis and exerting an anti-tumor effect. However, a randomized controlled clinical trial of apatinib combined with vinorelbine for triple-negative breast cancer (TNBC) has not been reported. We attempted to compare the therapeutic effect of vinorelbine alone or in combination with apatinib mesylate for patients with recurrent or metastatic TNBC who have received at least two drug treatments with anthracyclines and taxanes. Methods/analysis: This study is a triple-blind, randomized, placebo-controlled, parallel-group clinical trial. We plan to include 184 female patients with locally recurrent or metastatic TNBC admitted at the Liaoning Cancer Hospital & Institute, in Northeast China. All enrolled patients will be randomized to orally take vinorelbine alone (40 mg orally, thrice a week (Mondays, Wednesdays, and Fridays) in each 3-week cycle) or combined with apatinib mesylate (500 mg orally, once daily of each 3-week cycle). Radiographic assessment will be performed every 6 weeks for 36 weeks, and every 9 weeks thereafter. The primary outcome is measurement of progression-free survival and secondary outcomes include overall survival, disease control rate, objective response rate, and incidence of adverse events at grades 3 and 4 as defined by the National Cancer Institute Common Toxicity Criteria [NCI-CTC] Version 4.0. Outcome measures will be evaluated at baseline (< 2 weeks before starting treatment), every 6 weeks during treatment, and at 4 weeks and every 3 months after treatment discontinuation. Discussion: Based on the data from this trial, we hope to identify a treatment plan that is suitable for female TNBC patients in Northeast China who have been treated with anthracyclines and taxanes. Trial registration: ClinicalTrials.gov (identifier: NCT03932526). Registered on April 30, 2019.