Brennan Rachel C, Qaddoumi Ibrahim, Mao Shenghua, Wu Jianrong, Billups Catherine A, Stewart Clinton F, Hoehn Mary Ellen, Rodriguez-Galindo Carlos, Wilson Matthew W
Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
J Clin Oncol. 2017 Jan;35(1):72-77. doi: 10.1200/JCO.2016.69.2996. Epub 2016 Oct 31.
Purpose To evaluate topotecan-based therapy for advanced intraocular retinoblastoma. Patients and Methods Twenty-seven patients with bilateral retinoblastoma (male patients, n = 14; median age, 8.4 months) received chemotherapy: two courses of topotecan plus vincristine followed by three alternating administrations of carboplatin and vincristine for two courses and topotecan plus vincristine for one course, with optional periocular carboplatin. Focal therapy was applied after cycle 2. Event-free survival was defined as avoidance of external-beam radiotherapy (EBRT) and enucleation. Results Of 54 eyes, 42 were Reese-Ellsworth group IV to V, and 37 were International Classification of Retinoblastoma group C to E. Eleven eyes were enucleated: one at diagnosis, nine with progressive disease including three eyes treated with EBRT, and one that developed neovascular glaucoma after completion of therapy. One patient was removed from protocol with prolonged infection in course 1; 26 patients (51 eyes) were analyzed. At 10 years, cumulative incidence of EBRT was 5.9% (SE ± 3), and event-free survival was 69.2% (SE ± 27.2). Ocular survival for Reese-Ellsworth group IV to V eyes was 77.5% (SE ± 21.2); it was 74.3% (SE ≥ 18.8) for International Classification group C to E eyes. Vision testing (median age, 7 years; range, 5 to 10 years) documented 20/70 vision or better in one eye of 23 patients; 19 (76%) of 25 patients demonstrated 20/40 vision or better in one eye. All patients experienced thrombocytopenia (41 episodes in 275 courses; 15%). There were 29 episodes of febrile neutropenia (10%). Grade 3 diarrhea was present in nine of 27 patients, and one patient had an allergic reaction to carboplatin. All patients are alive at median follow-up 7.4 years (range, 2.7 to 10 years). Conclusion Topotecan combined with vincristine, carboplatin, and aggressive focal therapies is an effective regimen for the treatment of advanced retinoblastoma and results in globe salvage with vision. Toxicities were anticipated and managed with appropriate supportive care.
目的 评估基于拓扑替康的疗法用于晚期眼内视网膜母细胞瘤的疗效。患者与方法 27例双侧视网膜母细胞瘤患者（男性14例；中位年龄8.4个月）接受化疗：两个疗程的拓扑替康加长春新碱，随后交替给予三个疗程的卡铂和长春新碱，再进行一个疗程的拓扑替康加长春新碱，可选择眼周注射卡铂。在第2周期后进行局部治疗。无事件生存期定义为避免外照射放疗（EBRT）和眼球摘除。结果 54只眼中，42只为里斯-埃尔斯沃思分级IV至V级，37只为国际视网膜母细胞瘤分类C至E级。11只眼被摘除：1只在诊断时摘除，9只因疾病进展摘除，其中3只接受了EBRT治疗，1只在治疗完成后发生新生血管性青光眼。1例患者因第1疗程感染持续时间延长而退出研究方案；对26例患者（51只眼）进行分析。10年时，EBRT的累积发生率为5.9%（标准误±3），无事件生存期为69.2%（标准误±27.2）。里斯-埃尔斯沃思分级IV至V级眼的眼球保留率为77.5%（标准误±21.2）；国际分类C至E级眼为74.3%（标准误≥18.8）。视力测试（中位年龄7岁；范围5至10岁）显示，23例患者单眼视力达到20/70或更好；25例患者中有19例（76%）单眼视力达到20/40或更好。所有患者均出现血小板减少（275个疗程中有41次；15%）。有29次发热性中性粒细胞减少（10%）。27例患者中有9例出现3级腹泻，1例患者对卡铂过敏。中位随访7.4年（范围2.7至10年）时所有患者均存活。结论 拓扑替康联合长春新碱、卡铂及积极的局部治疗是治疗晚期视网膜母细胞瘤的有效方案，可实现眼球保留并保留视力。毒性反应可预期，并通过适当的支持治疗进行处理。
