Table 1.

Methods of targeting drugs to glioblastoma.

	Example agent	FDA approved	Advantages	Disadvantages
Oral	Temozolomide	Yes	Noninvasive administration	Systemic toxicity, myelosuppression
Intravenous	Bevacizumab	Yes	Minimally invasive administration	Systemic toxicity, CNS hemorrhage, and thromboembolic events
Local polymers	Carmustine implant (Gliadel)	Yes	Delivery directly to tumor resection bed	Craniotomy for implantation required, small volume of drug distribution, and relying on diffusion, seizure, and infection
Intra-arterial	Bevacizumab	No	Minimally invasive superselective delivery to tumor feeding arteries	High first-pass drug extraction necessary
Intraventricular	Methotrexate	No	Ideal for intraventricular and leptomeningeal disease	Neurotoxicity, aseptic meningitis, need for ventricular access device, and limited value for parenchymal tumor
Intrathecal	Methotrexate	No	Ideal for intraspinal and leptomeningeal disease	Neurotoxicity, aseptic meningitis, need for lumbar infusion, and limited value for parenchymal tumor
Microdialysis	Methotrexate	No	Limiting systemic and neurotoxicity, tissue delivery, and sampling possible	Small volume of drug distribution, relying on diffusion
Convection-enhanced	Topotecan	No	Limiting systemic and neurotoxicity, diffusion independent, and continuous infusion with implantable pumps possible	Surgical implantation required
Intranasal	Perillyl alcohol	No	Noninvasive administration	Unpredictable targeting and volume of distribution, mucosal irritation