A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis
Journal
BMC Cancer
Journal Volume
15
Journal Issue
1
Date Issued
2015
Author(s)
Wu P.-F.
Yeh D.-C.
Liao H.-W.
Huang S.-M.
Abstract
Background: Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer. Methods: Eligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed. Results: Eight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3-9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0-10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF. Conclusions: BEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease. ? Wu et al.; licensee BioMed Central.
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; bevacizumab; cisplatin; etoposide; vasculotropin; antineoplastic agent; bevacizumab; cisplatin; etoposide; adult; adverse outcome; aged; anemia; Article; breast cancer; cancer combination chemotherapy; carcinomatous meningitis; clinical article; controlled clinical trial; controlled study; disease association; drug blood level; drug cerebrospinal fluid level; drug efficacy; headache; human; hypertension; hyponatremia; inhibition kinetics; leukopenia; lymphocyte count; middle aged; multicenter study; multiple cycle treatment; neutropenia; neutrophil count; outcome assessment; overall survival; pilot study; progression free survival; prospective study; proteinuria; thrombocyte count; translational research; treatment response; animal; Breast Neoplasms; cancer staging; cerebrospinal fluid; clinical trial; complication; female; Meningeal Carcinomatosis; mouse; pathology; phase 2 clinical trial; randomized controlled trial; Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Cisplatin; Etoposide; Female; Humans; Meningeal Carcinomatosis; Mice; Middle Aged; Neoplasm Staging
Publisher
BioMed Central Ltd.
Type
journal article