Trachtenberg J, Bogaards A, Weersink R A, Haider M A, Evans A, McCluskey S A, Scherz A, Gertner M R, Yue C, Appu S, Aprikian A, Savard J, Wilson B C, Elhilali M
Department of Surgical Oncology, Ontario Cancer Institute/Princess Margaret Hospital/University Health Network, Toronto, Ontario, Canada.
J Urol. 2007 Nov;178(5):1974-9; discussion 1979. doi: 10.1016/j.juro.2007.07.036. Epub 2007 Sep 17.
Tookad is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external beam radiation therapy.
Patients received escalating drug doses of 0.1 to 2 mg/kg at a fixed light dose of 100 J/cm or escalated light doses of 230 and 360 J/cm at the 2 mg/kg dose. Four optical fibers were placed transperineally in the prostate, including 2 for light delivery and 2 for light dosimetry. Treatment response was assessed primarily by hypovascular lesion formation on contrast enhanced magnetic resonance imaging and transrectal ultrasound guided biopsies targeting areas of lesion formation and secondarily by serum prostate specific antigen changes.
Tookad vascular targeted photodynamic therapy was technically feasible. The plasma drug concentration was negligible by 2 hours after infusion. In the drug escalation arm 3 of 6 patients responded, as seen on magnetic resonance imaging, including 1 at 1 mg/kg and 2 at 2 mg/kg. The light dose escalation demonstrated an increasing volume of effect with 2 of 3 patients in the first light escalation cohort responding and all 6 responding at the highest light dose with lesions encompassing up to 70% of the peripheral zone. There were no serious adverse events, and continence and potency were maintained.
Tookad vascular targeted photodynamic therapy salvage therapy is safe and well tolerated. Lesion formation is strongly drug and light dose dependent. Early histological and magnetic resonance imaging responses highlight the clinical potential of Tookad vascular targeted photodynamic therapy to manage post-external beam radiation therapy recurrence.
Tookad是一种新型血管内光敏剂。当被763nm光激活时，它通过破坏肿瘤的血液供应来摧毁肿瘤。然后它会迅速从循环系统中清除。据我们所知，我们报告了Tookad血管靶向光动力疗法在人体中的首次应用。我们评估了其作为外照射放疗后的挽救性治疗的安全性、药代动力学和初步治疗反应。
患者接受固定光剂量100J/cm²下0.1至2mg/kg递增的药物剂量，或在2mg/kg剂量下接受230和360J/cm²递增的光剂量。四根光纤经会阴放置在前列腺中，其中两根用于光传输，两根用于光剂量测定。主要通过对比增强磁共振成像上的低血运病变形成以及经直肠超声引导下针对病变形成区域的活检来评估治疗反应，其次通过血清前列腺特异性抗原变化来评估。
Tookad血管靶向光动力疗法在技术上是可行的。输注后2小时血浆药物浓度可忽略不计。在药物递增组中，6名患者中有3名有反应，如磁共振成像所示，其中1名在1mg/kg剂量时有反应，2名在2mg/kg剂量时有反应。光剂量递增显示效应体积增加，在第一个光剂量递增队列中3名患者中有2名有反应，在最高光剂量时所有6名患者均有反应，病变累及外周区高达70%。没有严重不良事件，并且控尿和性功能得以维持。
Tookad血管靶向光动力疗法挽救性治疗是安全且耐受性良好的。病变形成强烈依赖于药物和光剂量。早期组织学和磁共振成像反应突出了Tookad血管靶向光动力疗法在处理外照射放疗后复发方面的临床潜力。
