Bevacizumab preconditioning followed by etoposide and cisplatin is highly effective in treating brain metastases of breast cancer progressing from whole-brain radiotherapy
Journal
Clinical Cancer Research
Journal Volume
21
Journal Issue
8
Pages
1851-1858
Date Issued
2015
Author(s)
Yeh D.-C.
Tseng L.-M.
Wu P.-F.
Rau K.-M.
Chao T.-C.
Huang S.-M.
Taiwan Breast Cancer Consortium
Abstract
Purpose: We hypothesized that a window period between bevacizumab and cytotoxic agents may enhance drug delivery into tumor tissue through bevacizumab-induced vascular normalization in patients with brain metastases of breast cancer (BMBC). Experimental Design: A single-arm phase II study was conducted in which BMBC patients refractory to whole-brain radiotherapy (WBRT) were enrolled. In a 21-day cycle, patients received bevacizumab (15 mg/kg) on day 1, which, with a 1-day window period, was followed by etoposide (70 mg/m2/day; days 2-4) and cisplatin (70 mg/m2; day 2; BEEP regimen). The BEEP regimen was administered for a maximum of 6 cycles. The primary endpoint was the central nervous system (CNS)-objective response rate according to volumetric response criteria. Results: A total of 35 patients were enrolled between January 2011 and January 2013. The median age was 54.3 years (range, 33-75); 19 patients (54.3%) had an Eastern Cooperative Oncology Group performance status of 2 or 3. Twenty-seven patients [77.1%; 95% confidence interval (CI), 59.9-89.6] achieved a CNS-objective response, including 13 patients (37.1%) with a ?80% volumetric reduction of CNS lesions. With a median follow-up of 16.1 months, the median CNS progression-free survival and overall survival times were 7.3 months (95% CI, 6.5-8.1) and 10.5 months (95% CI, 7.8-13.2), respectively. Common grade 3 or 4 toxicities included neutropenia (30.8%) and infection (21.3%). Conclusions: By administering bevacizumab 1 day before etoposide and cisplatin, the BEEP regimen appeared highly effective in BMBC refractory to WBRT. Further study of vascular normalization window concept is warranted. ?2015 American Association for Cancer Research.
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; bevacizumab; cisplatin; creatinine; etoposide; filgrastim; platinum complex; antineoplastic agent; bevacizumab; cisplatin; etoposide; tumor marker; adult; aged; anemia; Article; bleeding; brain metastasis; breast cancer; cancer growth; cancer radiotherapy; cancer survival; cerebellum infarction; clinical article; drug dose reduction; drug efficacy; drug response; drug safety; drug withdrawal; epigastric pain; fatigue; febrile neutropenia; female; human; hypertension; hypokalemia; hyponatremia; infection; leukopenia; maintenance chemotherapy; middle aged; multicenter study; multiple cycle treatment; nausea; neutropenia; outcome assessment; overall survival; phase 2 clinical trial; priority journal; progression free survival; proteinuria; side effect; survival time; Taiwan; thrombocytopenia; tracheoesophageal fistula; tumor volume; vomiting; whole brain radiotherapy; Brain Neoplasms; Breast Neoplasms; clinical trial; drug administration; mortality; multimodality cancer therapy; pathology; radiotherapy; secondary; treatment outcome; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Etoposide; Female; Humans; Middle Aged; Radiotherapy; Treatment Outcome
Publisher
American Association for Cancer Research Inc.
Type
journal article