The short-term outcome of intravitreal injection with topotecan for refractory vitreous seeding from retinoblastoma_Chinese Journal of Ocular Fundus Diseases

Authors：

Xia Jiejun , Fairooz , Jiang Hua , Liu Zhengyin , Tan Xiaoyun , Guo Yiqun ,  Zhang jing

Interventional & Vascular Anomalies Department, Guangzhou Women & Children Medical Center, Guangzhou 510623, China;

Corresponding author：

Zhang jing, Email: fejr@foxmail.com

Keywords：

Retinoblastoma; Vitreous seeding; Topotecan/therapeutic use

DOI：

10.3760/cma.j.issn.1005-1015.2018.05.009

Video：

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Objective To observe and evaluate the short-term therapeutic effect of intravitreal injection with topotecan for refractory vitreous seeding from retinoblastoma (RB)． Methods Eleven patients (11 eyes) of RB with refractory vitreous seeding (received intravenous chemotherapy, intra-arterial chemotherapy, intravitreal melphalan, laser, cryotherapy and subsequently developed refractory viable vitreous seeds) were enrolled in this study. There were 6 males (6 eyes) and 5 females (5 eyes). The aged from 9 to 44 months, with the mean age of 26 months. According to International Intraocular Retinoblastoma Classification, 11 eyes were initially classified as group E (3 eyes), D (6 eyes), B (1 eye) or A (1 eye). All patients were received intravitreal injection with topotecan. A total of 32 intravitreal topotecan injections were performed with a mean of 2.9 injections (median 3 injections; range 2−4 injections). The mean follow-up was 10 months. The safety and effectiveness of intravitreal injection with topotecan for refractory vitreous seeding from RB were observed. Results Complete regression of vitreous seeds was achieved in 11 of 11 eyes (100%), including complete disappearance in 9 eyes and fibrosis in 2 eyes. None of the patients needed enucleation and occured ocular or systemic complications in the follow-up period. Conclusion Intravitreal injection with topotecan for refractory vitreous seeds from RB is effective and safe.

Citation： Xia Jiejun, Fairooz, Jiang Hua, Liu Zhengyin, Tan Xiaoyun, Guo Yiqun, Zhang jing. The short-term outcome of intravitreal injection with topotecan for refractory vitreous seeding from retinoblastoma. Chinese Journal of Ocular Fundus Diseases, 2018, 34(5): 458-461. doi: 10.3760/cma.j.issn.1005-1015.2018.05.009 Copy

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2.	夏杰军, 张靖. 视网膜母细胞瘤经眼动脉灌注化学药物治疗研究进展[J]. 中华眼底病杂志, 2016,32(3): 330-333. DOI: 10.3760/cma.j.issn.1005-1015.2016.03.028.Xia JJ, Zhang J. The progress of intra-arterial chemotherapy for retinoblastoma[J]. Chin J Ocul Fundus Dis, 2016, 32(3): 330-333. DOI: 10.3760/cma.j.issn.1005-1015.2016.03.028.
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4.	Munier FL. Classification and management of seeds in retinoblastoma Ellsworth Lecture Ghent August 24th 2013[J]. Ophthalmic Genetics, 2014, 35(4): 193-207. DOI: 10.3109/13816810.2014.973045.
5.	Suzuki S, Aihara Y, Fujiwara M, et al. Intravitreal injection of melphalan for intraocular retinoblastoma[J]. Jpn J Ophthalmol, 2015,59(3): 164-172. DOI: 10.1007/s10384-015-0378-0.
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9.	Shields CL, Palamar M, Sharma P, et al. Retinoblastoma regression patterns following chemoreduction and adjuvant therapy in 557 tumors[J]. Arch Ophthalmol, 2009,127(3): 282-290. DOI: 10.1001/archophthalmol.2008.626.
10.	Linn Murphree A. Intraocular retinoblastoma: the case for a new group classification[J]. Ophthalmol Clin North Am, 2005,18(1): 41-53. DOI: 10.1016/j.ohc.2004.11.003.
11.	高翔, 王海燕, 王雨生. 复发或顽固性眼内视网膜母细胞瘤玻璃体腔化学药物治疗的现状与进展[J]. 中华眼底病杂志, 2016, 32(4): 449-453. DOI: 10.3760/cma.j.issn.1005-1015.2016.04.028.Gao X, Wang HY, Wang YS. The status and progress of intravitreal chemotherapy for resistant or recurrent retinoblastoma[J]. Chin J Ocul Fundus Dis, 2016, 32(4): 449-453. DOI: 10.3760/cma.j.issn.1005-1015.2016.04.028.
12.	Darsova D, Pochop P, Uhlik J, et al. Topotecan vitreous and plasma levels and retinal toxicity after transcorneal intravitreal delivery in healthy albino rabbits: alternative retinoblastoma treatment[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2012,156(4): 318-323. DOI: 10.5507/bp.2011.068.
13.	Furman WL, Stewart CF, Kirstein M, et al. Protracted intermittent schedule of topotecan in children with refractory acute leukemia: a pediatric oncology group study[J]. J Clin Oncol, 2002,20(6): 1617-1624. DOI: 10.1200/JCO.2002.20.6.1617.
14.	Schaiquevich P, Carcaboso AM, Buitrago E, et al. Ocular pharmacology of topotecan and its activity in retinoblastoma[J]. Retina, 2014,34(9): 1719-1727. DOI: 10.1097/IAE.0000000000000253.
15.	Munier FL, Gaillard MC, Balmer A, et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications[J]. Br J Ophthalmol, 2012,96(8): 1078-1083. DOI: 10.1136/bjophthalmol-2011-301450.
16.	Shields CL, Manjandavida FP, Arepalli S, et al. Intravitreal melphalan for persistent or recurrent retinoblastoma vitreous seeds: preliminary results[J]. JAMA Ophthalmol, 2014,132(3): 319-325. DOI: 10.1001/jamaophthalmol.2013.7666.
17.	Rao R, Honavar SG, Sharma V, et al. Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma[J]. Br J Ophthalmol, 2018, 102(4): 490-495. DOI: 10.1136/bjophthalmol-2017-310641.
18.	Ghassemi F, Shields CL, Ghadimi H, et al. Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma[J]. JAMA Ophthalmol, 2014,132(8): 936-941. DOI: 10.1001/jamaophthalmol.2014.414.
19.	Francis JH, Abramson DH, Ji X, et al. Risk of extraocular extension in eyes with retinoblastoma receiving intravitreous chemotherapy[J]. JAMA Ophthalmol, 2017,135(12): 1426-1429. DOI: 10.1001/jamaophthalmol.2017.4600.

1. Dimaras H, Kimani K, Dimba EA, et al. Retinoblastoma[J]. Lancet, 2012,379(9824): 1436-1446. DOI: 10.1016/S0140-6736(11)61137-9.
2. 夏杰军, 张靖. 视网膜母细胞瘤经眼动脉灌注化学药物治疗研究进展[J]. 中华眼底病杂志, 2016,32(3): 330-333. DOI: 10.3760/cma.j.issn.1005-1015.2016.03.028.Xia JJ, Zhang J. The progress of intra-arterial chemotherapy for retinoblastoma[J]. Chin J Ocul Fundus Dis, 2016, 32(3): 330-333. DOI: 10.3760/cma.j.issn.1005-1015.2016.03.028.
3. Abramson DH, Gobin YP, Marr BP, et al. Intra-arterial chemotherapy for retinoblastoma[J]. Ophthalmology, 2012, 119(8): 1720-1721. DOI:10.1016/j.ophtha.2012.03.039.
4. Munier FL. Classification and management of seeds in retinoblastoma Ellsworth Lecture Ghent August 24th 2013[J]. Ophthalmic Genetics, 2014, 35(4): 193-207. DOI: 10.3109/13816810.2014.973045.
5. Suzuki S, Aihara Y, Fujiwara M, et al. Intravitreal injection of melphalan for intraocular retinoblastoma[J]. Jpn J Ophthalmol, 2015,59(3): 164-172. DOI: 10.1007/s10384-015-0378-0.
6. Smith SJ, Smith BD. Evaluating the risk of extraocular tumour spread following intravitreal injection therapy for retinoblastoma: a systematic review[J]. Br J Ophthalmol, 2013,97(10): 1231-1236. DOI: 10.1136/bjophthalmol-2013-303188.
7. 董梅, 冯奉仪. 抗癌新药拓扑替康研究新进展[J]. 国外医学(肿瘤学分册), 2001, 28(1): 75-79. DOI: 10.3760/cma.j.issn.1673-422X.2001.01.026.Dong M, Feng FY. Topotecan: a novel anticancer drug[J]. Foreign Journal of Medical Oncology, 2001, 28(1): 75-79. DOI: 10.3760/cma.j.issn.1673-422X.2001.01.026.
8. Laurie NA. Topotecan combination chemotherapy in two new rodent models of retinoblastoma[J]. Clin Cancer Res, 2005,11(20): 7569-7578. DOI: 10.1158/1078-0432.CCR-05-0849.
9. Shields CL, Palamar M, Sharma P, et al. Retinoblastoma regression patterns following chemoreduction and adjuvant therapy in 557 tumors[J]. Arch Ophthalmol, 2009,127(3): 282-290. DOI: 10.1001/archophthalmol.2008.626.
10. Linn Murphree A. Intraocular retinoblastoma: the case for a new group classification[J]. Ophthalmol Clin North Am, 2005,18(1): 41-53. DOI: 10.1016/j.ohc.2004.11.003.
11. 高翔, 王海燕, 王雨生. 复发或顽固性眼内视网膜母细胞瘤玻璃体腔化学药物治疗的现状与进展[J]. 中华眼底病杂志, 2016, 32(4): 449-453. DOI: 10.3760/cma.j.issn.1005-1015.2016.04.028.Gao X, Wang HY, Wang YS. The status and progress of intravitreal chemotherapy for resistant or recurrent retinoblastoma[J]. Chin J Ocul Fundus Dis, 2016, 32(4): 449-453. DOI: 10.3760/cma.j.issn.1005-1015.2016.04.028.
12. Darsova D, Pochop P, Uhlik J, et al. Topotecan vitreous and plasma levels and retinal toxicity after transcorneal intravitreal delivery in healthy albino rabbits: alternative retinoblastoma treatment[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2012,156(4): 318-323. DOI: 10.5507/bp.2011.068.
13. Furman WL, Stewart CF, Kirstein M, et al. Protracted intermittent schedule of topotecan in children with refractory acute leukemia: a pediatric oncology group study[J]. J Clin Oncol, 2002,20(6): 1617-1624. DOI: 10.1200/JCO.2002.20.6.1617.
14. Schaiquevich P, Carcaboso AM, Buitrago E, et al. Ocular pharmacology of topotecan and its activity in retinoblastoma[J]. Retina, 2014,34(9): 1719-1727. DOI: 10.1097/IAE.0000000000000253.
15. Munier FL, Gaillard MC, Balmer A, et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications[J]. Br J Ophthalmol, 2012,96(8): 1078-1083. DOI: 10.1136/bjophthalmol-2011-301450.
16. Shields CL, Manjandavida FP, Arepalli S, et al. Intravitreal melphalan for persistent or recurrent retinoblastoma vitreous seeds: preliminary results[J]. JAMA Ophthalmol, 2014,132(3): 319-325. DOI: 10.1001/jamaophthalmol.2013.7666.
17. Rao R, Honavar SG, Sharma V, et al. Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma[J]. Br J Ophthalmol, 2018, 102(4): 490-495. DOI: 10.1136/bjophthalmol-2017-310641.
18. Ghassemi F, Shields CL, Ghadimi H, et al. Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma[J]. JAMA Ophthalmol, 2014,132(8): 936-941. DOI: 10.1001/jamaophthalmol.2014.414.
19. Francis JH, Abramson DH, Ji X, et al. Risk of extraocular extension in eyes with retinoblastoma receiving intravitreous chemotherapy[J]. JAMA Ophthalmol, 2017,135(12): 1426-1429. DOI: 10.1001/jamaophthalmol.2017.4600.

Chinese Journal of Ocular Fundus Diseases

The short-term outcome of intravitreal injection with topotecan for refractory vitreous seeding from retinoblastoma

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