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肿瘤治疗:光动力疗法CancerTherapy:PHOTODYNAMICTHERAPY徐克成广州复大肿瘤医院FUDACANCERHOSPITALOFGUANGZHOU中国广州GuangzhouCHINAPHOTODYNAMICTHERAPY(PDT)杀伤效应是三种基本作用的综合效应•直接杀伤肿瘤细胞•微血管损伤与循环障碍—缺血与缺氧•免疫反应局部作用与全身反应短期效应与长期影响Combinationof3-effectsScientifictherapy适应证美国、欧洲、日本和加拿大批准―――•食管癌（部分或完全梗阻）（改善率90%）•早期食管癌的根治（治愈率95%－100%）•早期肺癌（气管、支气管癌）的根治（治愈率90%）•梗阻性肺癌（气管或支气管癌）（改善率85%）•表浅性胃癌（治愈率95%）•早期宫颈癌和化生性增生（治愈率96%）研究证明有良好效果•Barrett食管伴高度不典型增生，食管腺癌临床报告有效•早期口腔癌、头颈部肿瘤、脑瘤（胶质瘤）、胸膜或腹膜间皮瘤、腹腔肉瘤、眼肿瘤、鼻咽癌、胸壁肿瘤、妇科癌肿、直肠癌、胆管癌、Kaposi肉瘤、皮肤癌。PhotoactivationPhotoactivation630nmlaser630nmlaserFiberopticFiberoptic630nm(nonthermal)630nm(nonthermal)Optional2ndlaserapplication96-120hourspostinjectionOptional2ndlaserapplication96-120hourspostinjectionPhotodynamicreactionkillscellsPhotodynamicreactionkillscellsRelativelyselectiveretentionofPHOTOFRIN®intumorcells40-50hourspostinjectionRelativelyselectiveretentionofPHOTOFRIN®intumorcells40-50hourspostinjectionPDT杀伤效应•肿瘤细胞凋亡•肿瘤细胞坏死PDT的概念肿瘤光敏剂在肿瘤治疗中的应用PHOTOFRIN®PDTinOncology•相对选择性,组织特异性•低毒性,安全,无免疫抑制,无骨髓抑制•治疗时间短•冷光化学反应,不影响其他治疗,与其他疗法相辅相成•可作多疗程,无药物耐药性•容易进行,操作较简单•病人痛苦小•疗效发生快•费用相对合理广州复大肿瘤医院PDT不良反应SideEffects•光敏感Photosensitivity•至少30天内可发生•取决于暴露光Dependentonphotobleaching–自然光易激发•反应类似于日光烧伤•发生率不一:20%•组织局部反应炎症局部疼痛•便秘广州复大肿瘤医院ChangeinesophagealepitheliumChangeinesophagealepitheliumSpecializedintestinalmetaplasia(SIM)Specializedintestinalmetaplasia(SIM)EndoscopicEndoscopicMicroscopicMicroscopicBarrett’sEsophagusBarrett’sEsophagusPhotofrinporfirmerPackageInsert.AxcanPharmaInc.2002.630nmwavelengthlaserlightapplication630nmwavelengthlaserlightapplicationEndoscopeEndoscopeFiberOpticGuideFiberOpticGuideHigh-GradeDysplasiaHigh-GradeDysplasiaLaserLightLaserLightCenteringBalloonCenteringBalloonPhotodynamicTherapy:Stage2PhotodynamicTherapy:Stage2PHOTOFRIN®(porfimersodium)forInjection.SeePrescribingInformation.AxcanPharmaInc.2003Pre-PDTPre-PDT48hoursPost-PDTPhotodynamicTherapyVisualPhotodynamicTherapyVisualDataonfilewithAxcanPharmaInc.7%14%39%52%77%59%0%20%40%60%80%100%AllDysplasiaAllDysplasiaBE&allDysplasiaBE&allDysplasiaHigh-GradeDysplasiaHigh-GradeDysplasiaHGDPatients(%)HGDPatients(%)AblationPost-TreatmentAblationPost-TreatmentPDT+Omeprazole(N=138)PDT+Omeprazole(N=138)Omeprazoleonly(N=70)Omeprazoleonly(N=70)AblationResponsePhase3Study:Intent-to-TreatAblationResponsePhase3Study:Intent-to-TreatDataonfilewithAxcanPharmaInc.OverallClinicalResponse>Follow-upof24monthsOverallClinicalResponse>Follow-upof24monthsp<0.0001p<0.0001LowerThirdoftheEsophagusLowerThirdoftheEsophagusENDOSCOPICPROCEDURECONSIDERATIONS:ENDOSCOPICPROCEDURECONSIDERATIONS:EndoscopicProceduresEndoscopicProceduresStentsNd:YAGPDTPDTwithPHOTOFRIN®:LocalizedCytotoxicityPDTwithPHOTOFRIN®:LocalizedCytotoxicitySelectivedeliveryofLightSelectivedeliveryofLightRelativelyselectiveretentionofPHOTOFRIN®intumortissueRelativelyselectivereten...