Table 2.

Strategies that induce transient disruption of the BBB in conjunction with intravenous and/or intra-arterial chemotherapy: clinical impact based on expectations from drug therapy^a

Strategy	Effectiveness for CNS Malignancy	Toxicity/Adverse Effects Profile	Introduction into Clinical Practice	Repeated/Continuous Administration	Tumor Size and CNS Location
Osmotic BBB disruption (IA mannitol)	Not established (only phase II studies)	Invasive procedure. May be associated with SAE. Frequency varies	Limited. Requires multidisciplinary expert team approach	Feasible but limited by invasiveness of the procedure	Safety limited by tumor size, mass effect, and location
Biochemical disruption of the BBB (IA RMP-7)	Not established (only phase II studies)	Invasive procedure. Associated with SAE.	Clinical practice discontinued	Feasible but limited by invasiveness and toxicity of the procedure	Safety may be limited by tumor size, mass effect, and location
Focused ultrasound-mediated BBB disruption	No human studies (only small animals studies)	No human studies	No human studies	No human studies	Limited to small tumor size

Abbreviations: IA, intra-arterial; SAE, severe adverse events.

^aFor references, please see text.