Abramson David H, Dunkel Ira J, Brodie Scott E, Kim Jonathan W, Gobin Y Pierre
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Ophthalmology. 2008 Aug;115(8):1398-404, 1404.e1. doi: 10.1016/j.ophtha.2007.12.014. Epub 2008 Mar 14.
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.
Phase I/II clinical trial.
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.
Cannulation of the ophthalmic artery was performed by a femoral artery approach using microcatheters while the children were under anesthesia and anticoagulated. Chemotherapy (melphalan) was infused into the artery over a 30-minute period.
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.
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.
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.
开发一种技术，使我们能够反复对患有晚期视网膜母细胞瘤的幼儿的眼动脉进行插管，找到动脉内给予美法仑时对视网膜母细胞瘤可耐受且具有杀瘤作用的剂量，并研究这些儿童动脉内注射美法仑的局部眼部和全身副作用。
I/II期临床试验。
10名患有晚期视网膜母细胞瘤（里斯-埃尔斯沃思V级）且拟行眼球摘除术的儿童，进入经机构审查委员会批准的美法仑眼动脉灌注方案以避免眼球摘除。
在儿童麻醉并抗凝的情况下，通过股动脉途径使用微导管对眼动脉进行插管。化疗药物（美法仑）在30分钟内注入动脉。
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。
9例（共27次）成功对眼动脉进行插管，1例患者插管多达6次。每例均可见肿瘤、玻璃体内播散灶和视网膜下播散灶显著消退。未发生严重全身副作用（败血症、贫血、中性粒细胞减少、发热或死亡）。无需输血（红细胞或血小板）。3例患者出现结膜和眼睑水肿，未经治疗自行消退。对角膜前部、瞳孔或眼球运动无毒性作用。1只（先前接受过放疗）眼睛出现视网膜缺血；另一只眼睛动脉内化疗后无毒性，但近距离放疗后确实出现了放射性视网膜病变。除1例患者外，所有患者治疗后视力稳定或改善。视网膜电图通常较差（治疗的是晚期眼睛），但2例患者治疗后视网膜电图改善（视网膜脱离消退）。7只眼睛避免了眼球摘除。2只接受动脉内治疗的眼睛被摘除，病理检查未发现存活肿瘤。
我们为视网膜母细胞瘤患儿开发了一种直接眼动脉灌注美法仑的技术。该技术全身副作用极小（1例患者出现3级中性粒细胞减少），局部毒性也极小。在采用该技术治疗的前9例患者中，7只原本注定要被摘除的眼睛得以挽救。
