A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma - Initial results
A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma - Initial results
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DOI：
10.1016/j.ophtha.2007.12.014
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发表时间：
2008-08-01
期刊：
影响因子：
13.7
通讯作者：
Gobin, Y. Pierre
中科院分区：
文献类型：
--
作者：
Abramson, David H.;Dunkel, Ira J.;Gobin, Y. Pierre
目的：开发一种技术，使我们能够对患有晚期视网膜母细胞瘤的幼儿反复进行眼动脉插管，找到视网膜母细胞瘤动脉内给药时可耐受且具有杀肿瘤作用的马法兰剂量，并研究这些儿童动脉内注射马法兰的局部眼部和全身副作用。设计：I/II期临床试验。参与者：10名晚期视网膜母细胞瘤儿童(Reese-Ellsworth V) 需要摘除的眼睛被纳入机构审查委员会批准的眼动脉输注美法仑方案以避免摘除。方法：在儿童处于麻醉和抗凝状态下，使用微导管通过股动脉途径进行眼动脉插管。化疗（马法兰）在30分钟内注入动脉。主要指标：眼科检查、视网膜摄影和视网膜电图用于记录局部毒性，而体格检查和全血细胞计数用于测量全身毒性。结果：眼动脉成功插管9例（共27次），其中1例患者插管6次。每个病例中都观察到肿瘤、玻璃体种子和视网膜下种子的显着消退。没有发生严重的全身副作用（败血症、贫血、中性粒细胞减少、发烧或死亡）。不需要输血（红细胞或血小板）。三名患者出现结膜和眼睑水肿，但未经治疗即可消退。对角膜、眼前节、瞳孔或运动没有毒性。一只眼睛（之前接受过照射）出现视网膜缺血；另一只眼睛在动脉化疗后没有出现毒性，但在近距离放射治疗后确实出现了放射性视网膜病变。除 1 名患者外，所有患者治疗后视力均稳定或改善。视网膜电图通常较差（高级眼睛接受了治疗），但有 2 例患者在治疗后视网膜电图有所改善（视网膜脱离得到缓解）。七只眼睛避免了剜除。两只经过动脉内治疗的眼睛被摘除，病理学上没有发现存活的肿瘤。结论：我们开发了一种直接眼动脉输注美法仑治疗视网膜母细胞瘤儿童的技术。该技术具有最小的全身副作用（一名患者出现 3 级中性粒细胞减少症）和最小的局部毒性。在首批9例接受该技术治疗的病例中，7只注定要被摘除的眼睛被挽救。
Objective: To develop a technique that would allow us to cannulate repeatedly the ophthalmic artery of young children with advanced retinoblastoma, to find a dose of melphalan that would be tolerable and tumoricidal for retinoblastoma when given intraarterially, and to study the local ocular and systemic side effects of intraarterial melphalan in these children.Design: Phase I/II clinical trial.Participants: Ten children with advanced retinoblastoma (Reese-Ellsworth V) eyes who were indicated for enucleation were entered into an institutional review board-approved protocol of ophthalmic artery infusion of melphalan to avoid enucleation.Methods: Cannulation of the ophthalmic artery was performed by a femoral artery approach using micro-catheters while the children were under anesthesia and anticoagulated. Chemotherapy (melphalan) was infused into the artery over a 30-minute period.Main Outcome Measures: Ophthalmic examinations, retinal photography, and electroretinograms were used to document local toxicity, whereas physical examinations and complete blood counts were used to measure systemic toxicity.Results: The ophthalmic arteries were successfully cannulated in 9 cases (total, 27 times), as many as 6 times in 1 patient. Dramatic regression of tumors, vitreous seeds, and subretinal seeds were seen in each case. No severe systemic side effects (sepsis, anemia, neutropenia, fever, or death) occurred. No transfusions were required (red cells or platelets). Three patients developed conjunctival and lid edema that resolved without treatment. There was no toxicity to the cornea, anterior segment, pupil, or motility. One (previously irradiated) eye developed retinal ischemia; another eye had no toxicity after intraarterial chemotherapy but did develop a radiationlike retinopathy after brachytherapy. Vision stabilized or improved in all but 1 patient after treatment. Electroretinograms were generally poor (advanced eyes were treated), but in 2 cases, the electroretinogram improved after treatment (and resolution of a retinal detachment). Seven eyes avoided enucleation. Two intraarterially treated eyes were enucleated, with no viable tumors identified pathologically.Conclusions: We developed a technique of direct ophthalmic artery infusion of melphalan for children with retinoblastoma. The technique had minimal systemic side effects (one patient had grade 3 neutropenia) and minimal local toxicity. Among the first 9 cases treated with this technique, 7 eyes destined to be enucleated were salvaged.