Evaluation of combined bevacizumab and intraperitoneal carboplatin or paclitaxel therapy in a mouse model of ovarian cancer
- Dhaval K. ShahAffiliated withDepartment of Pharmaceutical Sciences, University at Buffalo, The State University of New York
- , Jean VeithAffiliated withDepartment of Pharmacology and Therapeutics, Roswell Park Cancer Institute
- , Ralph J. BernackiAffiliated withDepartment of Pharmacology and Therapeutics, Roswell Park Cancer Institute
- , Joseph P. BalthasarAffiliated withDepartment of Pharmaceutical Sciences, University at Buffalo, The State University of New York Email author
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To evaluate the pharmacokinetics of bevacizumab following IP and IV administration, and to investigate combined bevacizumab therapy (IP or IV) with IP paclitaxel or carboplatin in a mouse model of ovarian cancer.
Bevacizumab pharmacokinetics were investigated following IV or IP dosing, and mice bearing peritoneal A2780 xenografts were treated with vehicle, IV or IP bevacizumab, IP paclitaxel, IP paclitaxel with co-administration of IV or IP bevacizumab, IP carboplatin, and IP carboplatin with co-administration of IV or IP bevacizumab. Survival time was defined as the time to death or the time to reach 120% of baseline body weight.
Following IP administration, bevacizumab was rapidly absorbed and bioavailability was 92.8%. Median survival time, which was 33 days for control mice, was increased by 24% with IP paclitaxel. IP carboplatin failed to increase survival time when administered alone. IV and IP bevacizumab increased survival time by 42 and 33%. Combined bevacizumab and IP paclitaxel was superior to paclitaxel alone (P = 0.01 for IV and P = 0.04 for IP bevacizumab), and combined bevacizumab and IP carboplatin was superior to carboplatin alone (P = 0.002 for IV and P = 0.02 for IP bevacizumab). There were no significant differences in survival between groups receiving bevacizumab IV or IP, either alone (P = 0.586), in combination with paclitaxel (P = 0.467), or in combination with carboplatin (P = 0.149).
Following IP administration to mice, bevacizumab demonstrates rapid and near complete absorption. Bevacizumab therapy, initiated prior to IP carboplatin or paclitaxel administration, increased survival time significantly in mice, and results were not dependent on the route of bevacizumab administration (IV vs. IP).
KeywordsIntraperitoneal chemotherapy Ovarian cancer Anti-angiogenic therapy Pharmacokinetic Carboplatin Paclitaxel
- Evaluation of combined bevacizumab and intraperitoneal carboplatin or paclitaxel therapy in a mouse model of ovarian cancer
Cancer Chemotherapy and Pharmacology
Volume 68, Issue 4 , pp 951-958
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- Intraperitoneal chemotherapy
- Ovarian cancer
- Anti-angiogenic therapy
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- Author Affiliations
- 1. Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA
- 2. Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA