注射用HPPH剂量递增光动力治疗食管癌的Ⅰ期临床研究

PhaseⅠClinical Study of Photodynamic Therapy for Esophageal Cancer with Increasing Doses of HPPH

目的初步评价注射用焦叶绿酸己醚(2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a,HPPH)光动力治疗食管癌的有效性和安全性。方法纳入诊断明确的食管癌患者18例,经标准治疗失败、缺乏或拒绝标准治疗的食管癌患者18例,其中2.5 mg/㎡、3.0 mg/㎡、3.5 mg/㎡、4.0 mg/㎡和5.0 mg/㎡剂量组入组病例数分别为3例、3例、4例、6例和2例受试者。用药后(48±2)h接受波长665 nm激光照射,功率密度150 mW/c㎡,能量密度为150 J/c㎡。结果吞咽指数为0者3例,2例完全缓解(complete remission,CR),1例部分缓解(partial response,PR)。部分梗阻性食管癌3例,1例PR、2例疾病稳定(stable disease,SD)。严重梗阻性食管癌12例,28 d吞咽改善率63.6%(7/11,1例出组未评价),21 d吞咽改善率81.8%(9/11)。所有受试者均未出现皮肤光毒性。发生2例严重不良反应(severe adverse event,SAE),均为气管食管瘘,判定1例可能与治疗有关,1例与治疗可能无关。发生率超过20%的不良反应有疼痛(14/18)、咳嗽(5/18)、发热(5/18)。结论HPPH光动力治疗食管癌安全有效,值得进一步深入研究。

Objective To evaluate the efficacy and safety of photodynamic therapy with HPPH.Methods Totally 18 patients with esophageal cancer who had been diagnosed as esophageal cancer who failed,lacked or refused standard treatment were included.The number of patients in the 2.5 mg/㎡,3.0 mg/㎡,3.5 mg/㎡,4.0 mg/㎡ and 5.0 mg/㎡ dose groups were 3,3,4,6 and 2,respectively.After(48±2)hours,the patients were irradiated by 665 nm laser with a power density of 150 mW/c㎡ and an energy density of 150 J/c㎡.Results Three cases with 0 swallowing index,2 cases had complete remission(CR)and 1 case had partial response(PR).Three cases of partial obstructive esophageal cancer,1 case of partial response(PR)and 2 cases of stable disease(SD).Twelve cases of severe obstructive esophageal cancer,the improvement rate of dysphagia was 63.6%(7/11)in 28 days and 81.8%(9/11)in 21 days.There was no skin phototoxicity in all cases.Two cases of SAE occurred,both of which were tracheoesophageal fistula.It was determined that one case may be related to the treatment,and one case may not be related to the treatment.The incidence of adverse reactions more than 20%were pain(14/18),cough(5/18)and fever(5/18).Conclusions HPPH photodynamic therapy for esophageal cancer is safe and effective,which is worthy of further study.