Aggressive multimodality therapy based on a multicompartmental model of glioblastoma

Glioblastoma multiforme is composed of multiple cellular compartments with different morphologic, kinetic, metabolic, vascular, and genetic properties. Optimal therapy may consist of a variety of therapeutic strategies designed for individual compartments, administered in close temporal relation. These concepts may turn out to be valid for other solid tumors as well. Microwave-induced hyperthermia can be used to treat metabolically quiescent, relatively hypoxic, nondividing cells (Go) otherwise resistant to radiation and chemotherapy. Similarly, polychemotherapy can treat a broad spectrum of cell types if the blood-brain barrier can be circumvented. Radical surgery, repetitively applied, can be safely used to "set up" experimental agents if the operation microscope and laser are employed. A consecutive series of 74 adult patients with malignant astrocytoma were treated with primary resection, radiation therapy, and 1,3,-bis(2 chloroethyl) 1 nitrosourea chemotherapy. At recurrence, all patients were offered reoperation with the microscope and the laser prior to administration of phase-I agents--hyperthermia via an implantable miniature microwave antenna (6 cases); aziridinylbenzoquinone chemotherapy (13 cases); and blood-brain barrier reversal with dimethyl sulfoxide (DMSO) and polychemotherapy (9 cases). It was concluded that temperatures of 45 degrees C could be safely achieved and human tumors could not efficiently dissipate heat; that DMSO plus drug therapy could be tolerated but blood-brain barrier reversal demonstrated by us in animals could not be shown in humans; and that aggressive multimodality therapy and reoperation could produce a 40% 2-year survival rate for patients younger than 40 years.