Photodynamic therapy for malignant glioma by argon laser. Basic study and clinical trials.

Abstract

This study was designed to assess the therapeutic application of photodynamic or photoradiation therapy (PDT) using hematoporphyrin derivative (HPD) and argon laser for human glioma. Fluorescence assays of HPD were obtained using a microfluorescence photometer mounted on a microscope (Leitz, West Germany). An optimal time and exposure dose after injection of HPD were evaluated in the experimental brain tumors, 9L glioma cells implanted into the rat brain. An argon laser with 488 nm wavelength was used as a light source. The amount of HPD in the experimental brain tumor was large between 24 and 96 hours after injection of 10 mg/kg of HPD, and it was also confirmed in the human patients with glioma. The different experimental brain tumor treatment groups, using a dose of 383 joules/cm2. sec of HPD-PDT, were evaluated by mean life spans. They were 22 ± 6 days in a non-treated group, 27 ± 5 days in a group treated by operation or surgical removal alone, and 69 ± 5 days in a group given intraperitoneal and local administration of HPD and operation-PDT. An alteration of the tissue temperature during HPD-PDT exposure of 450 joules/cm2. sec was studied. Tissue temperature increased between 4°and 9°C within normal tissue 4 mm from the injured area. Sixteen patients with glioma were treated by HPD-PDT. All the patients underwent surgical removal of the tumor, followed by PDT 72 hours after intravenous injection of 5 mg/kg of HPD. The radiation exposure was between 243 and 1, 564 joules/cm2 ⋅sec. Six patients with malignant glioma revealed a recurrence of the tumor in the exposed area within 6 months after PDT. They received a low dose, less than 311 joules/cm2. sec, or had a large residual volume of the tumor after surgery. It is suggested that the argon laser exposure should be above 343 joules/cm2. sec in energy for a remaining tumor of small volume.