Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation.
Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation.
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发表时间：
1996-09
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通讯作者：
H. Chan;G. Deboer;J. Thiessen;A. Budning;J. Kingston;J. O'Brien;Gideon Koren;E. Giesbrecht;G. Haddad;Zulfukarali Verjee;J. Hungerford;V. Ling;B. Gallie
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作者：
H. Chan;G. Deboer;J. Thiessen;A. Budning;J. Kingston;J. O'Brien;Gideon Koren;E. Giesbrecht;G. Haddad;Zulfukarali Verjee;J. Hungerford;V. Ling;B. Gallie
没有放射治疗的化学疗法不能控制大多数眼内视网膜母细胞瘤，这可能是因为我们在视网膜母细胞瘤中发现的多药耐药P-糖蛋白的高表达。环孢菌素阻断P-糖蛋白诱导的长春新碱和替尼泊苷体外外排，并可能调节对卡铂的反应。为了避免RB 1生殖系突变的双侧视网膜母细胞瘤患者的眼部照射，这会导致高的第二恶性肿瘤发生率，我们在长春新碱-替尼泊苷-卡铂方案中加入了环孢菌素A，并通过局部治疗巩固化疗反应。我们将需要放射治疗、眼球摘除术或中心视力局灶性消融的患者评分为失败。在21例研究患者中，中位随访3.3年的总体无复发率为76%，新诊断的复发率为92%，既往治疗的复发性视网膜母细胞瘤为50%。我们的研究结果对于最不利的肿瘤与玻璃体种子（86%，在3.5年）是优于发表的成功率放疗类似的肿瘤，或放疗与相同的化疗没有环孢素（45%，在2.5年）。6年）。这些结果也超过了我们在19例同等低风险患者中使用类似化疗（无环孢菌素、局部治疗和/或放疗）的历史成功率（中位随访时间为5.6年，无复发率为37%，P = 0.032），其中16例既往未接受过治疗（无复发率也为37%，P = 0.012）。环孢菌素血药浓度越高，预计组织暴露量越大，结局越好。环孢菌素并没有增加通常的化疗毒性。这项临床研究表明，环孢菌素改善视网膜母细胞瘤化疗的长期反应，可能是通过一种以上的机制。
Chemotherapy without radiation has not controlled most intraocular retinoblastoma, perhaps because of the common high expression of multidrug resistance P-glycoprotein that we found in retinoblastoma. Cyclosporin blocks P-glycoprotein-induced efflux of vincristine and teniposide in vitro, and possibly modulates responses to carboplatin. To avoid eye irradiation in bilateral retinoblastoma patients with RB1 germline mutations, which incurs a high second malignancy rate, we added cyclosporin A to a vincristine-teniposide-carboplatin protocol and consolidated chemotherapy responses with focal therapy. We scored patients requiring irradiation, enucleation, or focal ablation of central vision as failures. In 21 study patients, the overall relapse-free rate at a median follow-up of 3.3 years was 76%, with a rate of 92% for newly diagnosed and 50% for previously treated, relapsed retinoblastoma. Our results for the most unfavorable tumors with vitreous seeds (86% at 3.5 years) are better than published success rates of irradiation for similar tumors, or irradiation with the same chemotherapy without cyclosporin (45% at 2. 6 years). These results also exceeded our historic success rate with similar chemotherapy without cyclosporin, focal therapy, and/or radiation in 19 equivalently poor-risk patients (relapse-free rate 37% at a median follow-up of 5.6 years, P = 0.032), 16 of whom were previously untreated (relapse-free rate also 37%, P = 0.012). A better outcome occurred with higher cyclosporin blood levels and projected tissue exposure. Cyclosporin did not enhance the usual chemotoxicity. This clinical study suggests that cyclosporin improves the long-term response of retinoblastoma to chemotherapy, possibly by more than one mechanism.