Reversible osmotic blood-barrier disruption in humans: Implications for the chemotherapy of malignant brain tumors

The blood-brain barrier seems to be an important factor in drug access to malignant brain tumors. Successful experimental reversible disruption of the blood-brain barrier in animals provided the basis for a clinical evaluation of osmotic disruption in five patients with primary and metastatic malignant brain tumors. Good to excellent blood-brain barrier disruption was achieved in four patients with a single nontransient complication, a superficial wound infection at the burr hole site in the first patient. Reversible, transient osmotic barrier disruption was achieved 15 times in five patients without additional toxicity. Computed tomography and radionuclide brain imaging were shown to be useful noninvasive monitors of the adequacy and extent of barrier disruption. These studies also provide further evidence that the barrier is at least partially intact in human tumors because in one patient a metastasis was seen only after barrier disruption.