Phase I trial of thermochemotherapy for brain malignancy.

High-grade primary and refractory brain tumors and metastases to the brain from other primary sites are associated with a grave prognosis. Treatment, usually palliative, consists of some combination of surgery, radiation, and chemotherapy. Recently, noninvasive hyperthermia by magnetic-loop induction has been safely used to treat patients with advanced cancer in extracranial sites. Both disease regression and disease stabilization have been observed. This technique was recently applied to brain tumors in an animal model, and its safety was again demonstrated. As a result, a Phase I trial of noninvasive localized hyperthermia in combination with intravenous chemotherapy has been carried out in ten patients whose primary or metastatic brain tumors failed to respond to standard therapy. Ten patients underwent 23 thermochemotherapy sessions using the magnetic-loop induction device. The median, maximum temperature of normal brain after 1 hour of hyperthermia was 41.1 degrees C (range, 38.6 degrees C-43.4 degrees C); the median, maximum temperature of brain tumor was 42.5 degrees C (range, 38.8 degrees C-46.3 degrees C) (P less than 0.01). The temperatures of both the normal brain and brain tumor were obtained during 18 treatments. The tumor temperature was greater than the normal brain temperature in 15 of 18 treatments. In 78% of the treatments, the measured tumor temperature reached at least 42 degrees C, whereas the normal brain reached 42 degrees C in only 13% of the treatments. These data demonstrate the "selective inability" of brain tumor tissue to dissipate heat. Vital signs, intracranial pressure, and neurologic status were monitored throughout the hyperthermia treatments. No mortality or increase in chemotherapeutic toxicity could be attributed to the thermochemotherapy. In addition, there were no local complications or permanent neurologic complications. Two patients with elevated intracranial pressure before therapy had transient neurologic deficits that may have been exacerbated by the hyperthermia. It is concluded that this new, noninvasive modality not only produced effective intracranial tumor heating, but could be performed safely with the proper precautions. Phase II trials are warranted.