Bevacizumab preconditioning followed by Etoposide and Cisplatin is highly effective in treating brain metastases of breast cancer progressing from whole-brain radiotherapy

• Published in: Clinical cancer research Vol. 21; no. 8; pp. 1851 - 1858
• Main Authors: Lu, Yen-Shen, Chen, Tom Wei-Wu, Lin, Ching-Hung, Yeh, Dah-Cherng, Tseng, Ling-Ming, Wu, Pei-Fang, Rau, Kun-Ming, Chen, Bang-Bin, Chao, Ta-Chung, Huang, Shu-Min, Huang, Chiun-Sheng, Shih, Tiffany Ting-Fang, Cheng, Ann-Lii
• Format: Journal Article
• Language: English
• Published: United States 15.04.2015
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab - administration & dosage; Bevacizumab - therapeutic use; Biomarkers, Tumor; Brain Neoplasms - mortality; Brain Neoplasms - secondary; Brain Neoplasms - therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cisplatin - administration & dosage; Combined Modality Therapy; Drug Administration Schedule; Etoposide - administration & dosage; Female; Humans; Middle Aged; Radiotherapy; Treatment Outcome
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-14-2075

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). 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/m(2)/day; days 2-4) and cisplatin (70 mg/m(2); 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. 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%). 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.