Reply to Ciccolini et al.: Using mathematical modeling to predict response to antiangiogenic therapy in cancer patients

Autor: Duda, D. G., Heist, R. S., Sahani, D. V., Stylianopoulos, T., Engelman, J. A., Jain, R. K.
Přispěvatelé: Stylianopoulos, T. [0000-0002-3093-1696]
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Oncology
Vascular Endothelial Growth Factor A
Pathology
cancer patient
Lung Neoplasms
Letter
Angiogenesis Inhibitors
Carboplatin
Clinical study
chemistry.chemical_compound
paclitaxel
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
Monoclonal
Medicine
cancer survival
Non-Small-Cell Lung
Humanized
antineoplastic agent
Multidisciplinary
Neovascularization
Pathologic
Antiangiogenic therapy
mathematical parameters
Middle Aged
Vascular normalization
Bevacizumab
female
priority journal
carboplatin
Female
Non small cell
Vascular function
medicine.drug
medicine.medical_specialty
Paclitaxel
Antibodies
Monoclonal
Humanized
cancer chemotherapy
Antibodies
male
Albumins
Internal medicine
cancer combination chemotherapy
Biomarkers
Tumor
Humans
Letters
human
Neovascularization
antagonists and inhibitors
tumor blood flow
Pathologic
non small cell lung cancer
business.industry
Carcinoma
Cancer
treatment response
medicine.disease
drug efficacy
angiogenesis inhibitor
chemistry
antiangiogenic therapy
monoclonal antibody
vasculotropin A
business
mathematical model
Zdroj: Proceedings of the National Academy of Sciences of the United States of America
Popis: Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non-small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment-while reducing blood flow, volume, and permeability in the overall population-may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy.
Databáze: OpenAIRE
Externí odkaz: