Intratumoral Injections of Bevacizumab Could Help Prevent AEs Associated With Systemic Therapy

The Center for Biosimilars Staff

Intravenous administration of the anti–vascular endothelial growth factor treatment bevacizumab at high doses can result in serious, systemic adverse events (AEs). Additionally, tumors can become resistant to therapy and adopt a more invasive growth pattern. Thus, delivering bevacizumab for the treatment of cancer at a lower dose in a manner that avoids systemic AEs is necessary.

Intravenous administration of the anti—vascular endothelial growth factor treatment bevacizumab at high doses can result in serious, systemic adverse events (AEs). Additionally, tumors can become resistant to therapy and adopt a more invasive growth pattern. Thus, delivering bevacizumab for the treatment of cancer at a lower dose in a manner that avoids systemic AEs is necessary.

A recent study, published in OncoTargets and Therapy, sought to evaluate the therapeutic effect of intratumoral low-dose bevacizumab versus high-dose treatment in glioma-bearing animals, and found that administering bevacizumab by intratumoral injection might be an effective protocol for treating gliomas by regulating the expression of inflammation and invasion-related factors and inhibiting cancer stem cells.

In mice implanted with glioma cells, researchers found that bevacizumab delivered by intratumoral injection or systemic (intravenous) administration was effective, but intratumoral injection was more efficient; the bioluminescence imaging signal used to assess tumor growth in mice treated intratumorally was less intense than it was in those treated with intravenous therapy.

Injected bevacizumab was also associated with increased survival; mice that received intratumoral injections had a median survival of 40 days versus 27 days in the intravenous therapy group.

The density of tumor blood vessels was also reduced in mice who received injections, as were invasive factors of tumors and cancer stem cells, versus mice who received systemic therapy. However, inflammatory factors of tumors increased in the injection group; cold-inducible RNA-binding protein, which mediates brain injury, was significantly increased in the injected group versus the systemic therapy group.

The authors concluded that localized delivery of bevacizumab was more effective in reducing tumor size and cell infiltration versus intravenous delivery, and could be considered an alternative to intravenous therapy. While more research will be necessary, the identification of this possibility serves as a first step, write the authors, to a novel delivery method that could overcome the AEs associated with systemic therapy.

Reference

Liu YX, L WJ, Zhang HR, Zhang ZW. Delivery of bevacizumab by intracranial injection: assessment in glioma model. Onco Targets Ther. 2018;11:2673-2683. doi: 10.2147/OTT.S159913.