A phase IIa study of light-activated talaporfin sodium in patients with primary or recurrent glioblastoma multiforme

Abstract

e13026 Background: Preclinical studies have shown that talaporfin sodium (LS11) can concentrate in brain-tumor cells and be activated by red light (664nm wavelength) from light-emitting diodes (LEDs). Singlet oxygen is released that induces blood-vessel occlusion and apoptosis in target tumor cells, which results in direct tumor-cell death and a potential antitumor immunogenic effect on untreated tumors. Preferential talaporfin uptake in tumor and clearance from normal surrounding brain occur by 24 hours after injection. A single center, open label phase IIa study was conducted to establish safety and acute antitumor effect of light-activated drug therapy in glioblastoma patients. Methods: Nine patients (Karnofsky score >90) with operable glioblastoma, four of which were recurrent in the right frontal or temporal lobe, were recruited at a neurosurgical center in Belgrade, Serbia. Tumor diameter ranged 4–9 cm. Treatment consisted of IV injection of 1mg/kg of LS11 with subsequent craniotomy after a 24-hour wait. A single LED device was inserted into the tumor center followed by different light doses, 250 joules in six patients and 500 joules in three patients. Treated tumors were then resected. Patients were assessed for 4 weeks with serial CT imaging, intracranial pressure monitoring, and clinical, neurologic, and lab examination. Results: No dose-limiting toxicity was noted at the higher light-dose level. Seven adverse events (2 neurologic) occurred in four patients, none treatment related. Apoptosis was evident by TUNEL stain, and vessel closure was seen histologically. No acute inflammatory changes or cerebral edema were noted; normal brain was unaffected. No adverse neurologic sequelae were ascribable to the therapy, and no post-operative ICP elevation was noted. At 4 weeks, all patients were alive; two patients progressed and died shortly thereafter. Conclusions: Treatment of glioblastoma with this light-activated drug therapy was safe and tolerable in this study. An antivascular effect and tumor-cell apoptosis were seen histologically and confined to tumor. [Table: see text]