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Vladimir Kratky, Ashley Minuk, Christine Law, Isabella Irrcher; Systemic absorption of bevacizumab after subcutaneous eyelid skin injection: an animal study.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3118.
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The standard of care for BCC, the most common malignant tumour of the skin, is surgical excision. Approximately 5% of cases recur, and patients with multiple excisions may run out of available skin for flaps or appropriate donor sites. Although BCC rarely metastasizes, it is locally destructive and can cause significant morbidity if left untreated. Basal cell carcinoma and its surrounding microtumour environment have been shown to enhance the biological activity of VEGF. Our group has been investigating the utility of targeting VEGF as a therapeutic option for BCC patients who are unable or unwilling to undergo surgical excision. However, no research elucidates the systemic effect of subcutaneous bevacizumab injection. The purpose of this study is to evaluate the systemic absorption of bevacizumab in a pre-clinical model.
The left lower eyelid of 8 New Zealand white rabbits was injected subcutaneously with high (10mg; n=4 animals) and low (5mg; n=4 animals) doses of Bevacizumab .. The rabbits were examined weekly up to 5 weeks and adverse events were recorded. Systemic levels of Bevacizumab were evaluated in rabbit serum pre-injection, at 1, 2, 8, and 24 hours and at 1, 3, and 5 weeks post-injection.
There were no adverse events at any time point. A repeated measure one-way ANOVA comparing serum concentrations of bevacizumab at different time points in the high dose group showed a significant main effect of drug [F(7,2)=43.47; p<0.0001]. Post hoc analyses using Dunnett’s HSD test indicated that serum concentrations were significantly higher than pre-injection concentrations at all measured time points except at 3 and 5 weeks post-injection.
Though serum Bevacizumab levels were significantly increased following injection of 10mg, the maximum measured serum levels were less than 50% of the published levels following intravitreal injection of 1.25mg, which does not cause significant side effects in animals. Thus, subcutaneous Bevacizumab for the treatment of eyelid BCC may be a viable alternative for the treatment of BCC in humans with negligible systemic dissemination.
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