A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer
Journal
BMC Cancer
Journal Volume
16
Journal Issue
1
Date Issued
2016
Author(s)
Abstract
Background: To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Methods: Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60, and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2-4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. Results: Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were -12.8 and -24.7 % for Peak, -46.6 and -65.8 % for Slope, -27.9 and -55.5 % for iAUC 60, and -46.6 and -63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. Conclusion: Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. Trial registration: ClinicalTrials.gov, identifier NCT01281696 , registered prospectively on December 24, 2010 ? 2016 The Author(s).
SDGs
Other Subjects
bevacizumab; cisplatin; epidermal growth factor receptor 2; estrogen receptor; etoposide; angiogenesis inhibitor; antineoplastic agent; bevacizumab; cisplatin; contrast medium; etoposide; adult; aged; Article; brain metastasis; breast cancer; cancer survival; clinical article; contrast enhancement; dynamic contrast enhanced magnetic resonance imaging; human; multicenter study (topic); multiple cycle treatment; nuclear magnetic resonance imaging; phase 2 clinical trial (topic); pilot study; prospective study; tumor vascularization; tumor volume; Brain Neoplasms; Breast Neoplasms; clinical trial; diagnostic imaging; drug administration; drug resistance; female; middle aged; pathology; phase 2 clinical trial; procedures; secondary; time factor; treatment outcome; vascularization; Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Breast Neoplasms; Cisplatin; Contrast Media; Drug Administration Schedule; Drug Resistance, Neoplasm; Etoposide; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Pilot Projects; Prospective Studies; Time Factors; Treatment Outcome
Publisher
BioMed Central Ltd.
Type
journal article