Photodynamic Therapy for the Treatment of Vertebral Metastases: A Phase I Clinical Trial

Abstract

Purpose: Vertebroplasty (VP) and balloon kyphoplasty (KP) are minimally invasive stabilization procedures for pathologic vertebral compression fractures (VCF). Concurrent administration of photodynamic therapy (PDT) as a tumor-ablative modality has yet to be studied in humans as a potential complement to improved mechanical stability that is afforded by vertebral cement augmentation (VCA). Patients and Methods: This first-inhuman trial used a single 6 mg/m 2 dose of the clinical photosensitizer Visudyne with escalating laser light doses. Following a cohort of lightonly controls (n ¼ 6), the drug and light treatment groups (n ¼ 6 each) were 50, 100, 150, and 200 J/cm. VCA was performed within 15 minutes following PDT. Patients were clinically reviewed at 1 and 6 weeks. The primary outcome measure was safety from a neurologic perspective. Results: Thirty patients comprising a variety of primary tumors were treated with PDT and either KP or VP. Vertebral PDT was technically feasible and delivered in all study patients. No dose groups showed significant increases in pain as defined by the generic SF-36 as well as disease-specific EORTC-QLQ-BM22 and EORTC-QLQ-C15-PAL questionnaires. The 50 and 100 J/cm groups showed the most significant pain reduction (P < 0.05). Twelve (40%) patients experienced complications during the study including 3 patients with further vertebral fracture progression by 6 weeks despite VCA. No complications were directly attributed to PDT. Conclusions: Using the parameters described, vertebral PDT as an adjunct to VCA is safe from a pharmaceutical and neurologic perspective. The results of this trial motivate scaleup study evaluating potential PDT efficacy in vertebral metastatic treatment.

Progress of Phototherapy Applications in the Treatment of Bone Cancer

“…Patients treated with PDT under the light from interstitial diffusing fiber at 50 or 100 J/cm felt pain significantly reduced, and no complications directly attributed to PDT were found. These results suggested that VP or KP combined with PDT is safe and can shorten the hospital stay [ 187 ]. Moreover, photochemotherapy based on photochemical internalization (PCI) has been developed for clinical use.…”

Engineering naphthalimide-cyanine integrated near-infrared dye into ROS-responsive nanohybrids for tumor PDT/PTT/chemotherapy

“…Therefore, they are considered as emerging treatments for various tumour ablations. Porphyrin, chlorin, phthalocyanine, boron-dipyrromethene and cyanine derivatives are frequently applied as phototherapeutic agents in preclinical and clinical trials, such as verteporfin [ 7 ], bromoaza dipyrromethane ADPM06 [ 8 ], indocyanine green (ICG) [ 9 , 10 ]. Nevertheless, the development of structurally diverse near-infrared dyes is of great significance and faces many challenges.…”

Assessment of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy on Bone Metastases: An in Vitro Study

“…In the context of vertebral tumors, PDT was not only effective in ablating cancerous lesions [21], but also in enhancing the vertebral structure (particularly when combined with bisphosphonates) [22]. In fact, a recently completed phase I clinical trial showed that the combination of vertebral metastasis PDT and vertebral cement augmentation is not only safe from a pharmaceutical and neurologic perspective but also proved highly effective in pain reduction [23]. Such promising results further advocate for a scale-up study to evaluate the potential PDT efficacy in metastatic treatment [23].…”

“…In fact, a recently completed phase I clinical trial showed that the combination of vertebral metastasis PDT and vertebral cement augmentation is not only safe from a pharmaceutical and neurologic perspective but also proved highly effective in pain reduction [23]. Such promising results further advocate for a scale-up study to evaluate the potential PDT efficacy in metastatic treatment [23]. Until recently, the efficacy of PDT in treating a deep-seated tumor was limited due to a low light penetration depth, low oxygen concentration in the hypoxic core, and poor photosensitizer accumulation inside the tumor.…”