Use of an Anti-Vascular Endothelial Growth Factor Antibody in a Pharmacokinetic Strategy to Increase the Efficacy of Intraperitoneal Chemotherapy

摘要: The efficacy of intraperitoneal chemotherapy for ovarian cancers is limited by poor penetration drug into peritoneal tumors. Based on pharmacokinetic theory that suggests depth primarily determined the rate removal via tumor capillaries, we have hypothesized co-administration antiangiogenic therapy will allow decreased removal, increased concentrations in tumor, and chemotherapy. Pharmacokinetic modeling was conducted to simulate effect blood flow topotecan. Simulations predicted reductions, as potentially achieved therapy, would lead substantial increases after but a slight decrease systemic studies performed using A2780 xenograft model showed animals receiving combined topotecan an anti-vascular endothelial growth factor (VEGF) monoclonal antibody had ∼6.5-fold higher (p = 0.0015) compared with alone, whereas there no significant 0.16) difference Therapeutic two different drugs, cisplatin, anti-VEGF displayed superior survival relative treated alone (i.e., cisplatin or topotecan), intravenous concomitant therapy. Combined resulted complete cure four 11 mice. proposed combination chemotherapy, which be beneficial simulations, may provide benefit patients malignancies.