Gallie B L, Budning A, DeBoer G, Thiessen J J, Koren G, Verjee Z, Ling V, Chan H S
Department of Ophthalmology, Faculty of Pharmacy, University of Toronto.
Arch Ophthalmol. 1996 Nov;114(11):1321-8. doi: 10.1001/archopht.1996.01100140521001.
External beam radiotherapy is standard treatment for medium and large, or visually threatening, intraocular retinoblastoma but markedly increases the risk of cosmetic deformities and second malignant neoplasms in children with germline RB1 mutations. Large tumors and those with vitreous seeds do poorly despite radiotherapy. Chemotherapy traditionally is ineffective for intraocular retinoblastoma, perhaps because many retinoblastomas overexpress the multidrug resistance protein, P-glycoprotein.
To avoid radiotherapy in the management of intraocular retinoblastoma by using chemotherapy and focal therapy.
We shrank retinoblastomas in 40 eyes of 31 patients that conventionally should be enucleated or receive radiotherapy by using chemotherapy (ie, vincristine-teniposide, 8 eyes; additional carboplatin, 32 eyes) combined with the administration of cyclosporine, a known multidrug-resistance-reversal agent. We then consolidated these responses to chemotherapy by subsequent 532- and 1064-nm laser therapy and cryotherapy.
At the median follow-up of 2 2/3 [corrected] years (range, 1/10-4 3/4 years), the results of treatment were excellent. The actuarial relapse-free rate was 89% in patients not previously treated (91% for 28 eyes) and 67% in patients treated after relapse from previous therapy (70% for 12 eyes). For the eyes with the worst prognosis (ie, vitreous seeds), the relapse-free rate was 88%, better than previously reported. Cyclosporine is nontoxic and did not enhance the expected toxic effects of chemotherapy. Most eyes required laser therapy, cryotherapy, or both for consolidation of tumor control.
This pilot study suggests that most retinoblastomas are curable by combining chemotherapy with cyclosporine therapy, laser therapy, and cryotherapy, without requiring external beam radiotherapy. We propose a randomized trial to clarify the role of cyclosporine.
对于中大型或有视力威胁的眼内视网膜母细胞瘤，外照射放疗是标准治疗方法，但这会显著增加携带种系RB1突变儿童出现美容畸形和继发恶性肿瘤的风险。尽管进行了放疗，大肿瘤以及伴有玻璃体种植的肿瘤预后仍较差。传统上，化疗对眼内视网膜母细胞瘤无效，这可能是因为许多视网膜母细胞瘤过度表达多药耐药蛋白P-糖蛋白。
通过使用化疗和局部治疗避免在眼内视网膜母细胞瘤的治疗中进行放疗。
我们对31例患者的40只眼睛中的视网膜母细胞瘤进行缩小，这些眼睛按照常规应该进行眼球摘除术或接受放疗，方法是使用化疗（即长春新碱-替尼泊苷，8只眼；加用卡铂，32只眼）并联合给予环孢素，一种已知的多药耐药逆转剂。然后通过后续的532纳米和1064纳米激光治疗以及冷冻疗法巩固这些对化疗的反应。
在中位随访2 2/3[校正后]年（范围1/10 - 4 3/4年）时，治疗结果极佳。未接受过先前治疗的患者的无病生存率为89%（28只眼中91%），先前治疗复发后接受治疗的患者为67%（12只眼中70%）。对于预后最差的眼睛（即伴有玻璃体种植），无病生存率为88%，优于先前报道。环孢素无毒，且未增强化疗预期的毒性作用。大多数眼睛需要激光治疗、冷冻治疗或两者联合以巩固肿瘤控制。
这项初步研究表明，通过将化疗与环孢素治疗、激光治疗和冷冻治疗相结合，大多数视网膜母细胞瘤是可以治愈的，无需外照射放疗。我们提议进行一项随机试验以阐明环孢素的作用。
