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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2008

01-04-2008 | Original Article

Pharmacokinetics and safety of bevacizumab administered in combination with cisplatin and paclitaxel in cynomolgus monkeys

Authors: Lu Xu, Christina L. Zuch, Yvonne S. Lin, Nishit B. Modi, Bert L. Lum

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2008

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Abstract

Purpose

Bevacizumab is the first anti-angiogenic monoclonal antibody approved for use in combination with chemotherapy for treatment of a variety of solid tumors. The objective of this study was to evaluate the safety of bevacizumab when administered concomitantly with paclitaxel and cisplatin to cynomolgus monkeys, and to assess the pharmacokinetic and safety interactions between bevacizumab and the two chemotherapeutic agents.

Methods

Twenty male cynomolgus monkeys (Macaca fasicularis) were randomized to one of four treatment groups: vehicle, bevacizumab alone, cisplatin alone, and the combination of cisplatin and bevacizumab. Blood collection over serial time points allowed determination of the pharmacokinetic parameters of paclitaxel and bevacizumab and the maximum concentration (C max) for cisplatin. Drug concentrations were determined by graphite-furnace atomic absorption, high performance liquid chromatography, and enzyme-linked immunosorbent assay methods, for cisplatin, paclitaxel, and bevacizumab, respectively.

Results

AUC0-t values for bevacizumab when administered alone or in combination with chemotherapy were 6,747 ± 1,872 and 7,366 ± 1,599 μg/ml × day, respectively. AUC0-t values for paclitaxel with or without concomitantly administered bevacizumab were 10.9 ± 2.9 and 10.3 ± 3.7 μg/ml × day, respectively. No alterations in the C max of bevacizumab, paclitaxel, or cisplatin were observed between any of the treatment groups. As expected, based on their known safety profile, the administration of cisplatin and paclitaxel were associated with vomiting, decreased body weight, and transient decreases in white blood cell and absolute neutrophil counts; concomitant bevacizumab administration did not alter the incidence or severity of these toxicological effects.

Conclusion

Pharmacokinetic estimates for bevacizumab, paclitaxel and cisplatin indicate that combination of bevacizumab with the two chemotherapeutic agents does not result in a pharmacokinetic interaction. Moreover, the addition of bevacizumab to the chemotherapy regimen did not appear to alter the safety profiles of cisplatin/paclitaxel in cynomolgus monkeys. Results from the present study supported the clinical development of bevacizumab treatment regimens in combination with the chemotherapeutic agents paclitaxel and cisplatin.
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Metadata
Title
Pharmacokinetics and safety of bevacizumab administered in combination with cisplatin and paclitaxel in cynomolgus monkeys
Authors
Lu Xu
Christina L. Zuch
Yvonne S. Lin
Nishit B. Modi
Bert L. Lum
Publication date
01-04-2008
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2008
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-007-0513-9

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