Journal de neuro-oncologie et de neurosciences Libre accès

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Intraoperative Sono-photodynamic Therapy with Photolon in Animal Experiments and Promising Results of Phase I Clinical Study in Patients with Recurrent Malignant Gliomas

Istomin Yu, Tzerkovsky D, Grachev Yu, Artsemyeva T, Borichevsky F, Maslakov E, Semak I and Bagrintsev D

Aim: Evaluate the efficacy and safety of intraoperative sono-photodynamic therapy (iSPDT) with photosensitizer photolon in rats with orthotopic C6 glioma and then to test this therapy in patients with recurrent malignant gliomas.

Materials and methods: The experimental study was performed on 5 groups of rats bearing C6 glioma: untreated control, tumor resection (TR) only, TR+intraoperative sonodynamic therapy (iSDT), TR+intraoperative photodynamic therapy (iPDT) and TR+iSPDT. Photolon was injected intravenously shortly before TR that was followed by iSDT and iPDT. The criterium of treatment effeicacy was median overall survival (OS) of the animals. The clinical Phase I study comprised 15 patients with recurrent malignant gliomas. The first stage of the treatment was total/subtotal TR followed by intravenous administration of photolon; then the tumor bed was consequtively exposed to ultrasound (1.04 MHz; 1 W/cm²; 10 min.) and laser irradiation (50-100 J/cm²) 0.5 h after the start of photolon infusion. Within 4 weeks after discharge from hospital all patients underwent chemotherapy. The toxicity of anticancer therapies was evaluated on the basis of frequency and severity of adverse reactions accounted in accordance with CTCAE (Version 4.0). The criteria for assessing antitumor efficacy were: MRI images at 3 and 6 months after iSPDT treatment, median OS and post-iSPDT median times.

Results: TR+iSPDT of orthotopic C6 glioma increased the median OS of rats to 38 days in comparison with 18 days in the TR group (p=0.001); the combined effect of iSDT and iPDT was approximately additive. In the human patients, treatmentrelated toxicities were of grade I/II only. The median OS of died patients from first diagnosis was 23.9 months in iSPDT and 12.1 months in control group, respective (p=0.004). The post-iSPDT median survival was 8.2 month, while in the control group (without iSPDT) it was 5.8 month (p=0.012).

Conclusions: iSPDT with photolon may be considered as a fairly safe and potentially effective option for the adjuvant management of malignant brain tumors.