https://doi.org/10.31288/oftalmolzh201535968

Retinoblastoma intravitreal chemotherapy (five-year experience)

Bobrova N. F., Sorochinskaya T. A.

SI «Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Science of Ukraine»; Odessa (Ukraine)

Introduction. Local intravitreal chemotherapy (IVC) is one of the new retinoblastoma (RB) salvage eye methods. However, IVC indications, doses and algorithm of cytostatic application are still not developed, complications and efficacy of this method are not enough studied.

Purpose. To study the short-term and long-term results of IVC in RB complex salvage eye treatment.

Material and methods. IVC was Melphalan was given to 67 children aged 2 -14 y/o (average 19.2±16.5 mo) inn 91 eyes with RB T1 — T3b stages. 2 groups were selected depending on a dose and IVC method: the 1st group (16 eyes) — the dose was 0.015mg of Melphalan in 1 injection secondary in pretreated RB cases, the 2nd group (75 eyes) — the dose was 0.01 mg of Melphalan in 1 injection as primary therapy in combination with systemic chemoreduction [3]. Follow up from 2 to 5 years (average 20.3±9.1 mo) was in 32 patients (42 eyes).

Results. In the 1st group the amount of complications and enucleations was evidence of insufficient efficacy of the second IVC. In this connection the method of combined RB polychemotherapy (PCT) — primary IVC with Melphalan in the dose O.01 mg with simultaneous chemoreduction of CEV-protocol (Patent of Ukraine A61f 9/007 of 27.12.2010) and algorithm of its administration every 3 weeks with additional focal tumor destruction if necessary was developed. Complications were practically not observed except local retinal degeneration in the injection areas (15 eyes). 78.6 % of the eyes were preserved: in the T1-T2 stages — 100 %, T3 (including T3a-T3b) — 65.4 %.

Conclusion. Due to our five-year’s experience the developed method of primary IVC in combination with systemic Carboplatin PCT gives the greatest chance for eye and sight preservation with minimal amount of complications and cytostatic drug local and general toxic influence.

Key words: retinoblastoma, intravitreal chemotherapy, combined polychemotherapy

References

Avetisov ES, Kovalevskii EI, Khvatova AV. Guidelines for Pediatric Ophthalmology. M.: Meditsina; 1987. 496 p. 

Bobrova NF, Sorochinskaia TA. New trends in the treatment of retinoblastoma in children. Proceedings of International Scient. Conf. Боброва Н. Ф. ded. to 100th Ann. Of N. A. Puchkovskaia, Odessa. 2008. 25–60. In Russian. 

Bobrova N. F. The method of combined treatment of retinoblastoma. Potent of Ukraine 55690 U from 27.12.2010

Saakyan S. V. Modern approaches of treatment for retinoblastoma. Rossiiskii Ofatalmol Zhurnal. 2008;1:33–8. In Russian. 

Bobrova NF, Sorochinskaya TA. Local retinoblastoma chemotherapy by intravitreal Melphalan injections (the preliminary report). SE Eur J Ophthalmol. 2009;2 (3–4): 28–34.

Chan H, Gallie B, Munier F, Beck Popovic M. Chemotherapy for retinoblastoma. Ophthalmol Clin North Am. Mar 2005;18(1):55–63 
Crossref

Durairaj C, Shah JC, Senapati S, Kompella UB. Prediction of vitreal half-life based on drug physicochemical properties: quantitative structure–pharmacokinetic relationships (QSPKR). Pharm Res.2009;26:1236–1260.
Crossref

Edelhauser HF, Boatright JH, Nickerson JM and the Third ARVO/Pfizer Research Institute Working Group. Drug delivery to posterior intraocular tissues: third annual ARVO/Pfizer ophthalmics research institute conference. Invest Ophthalmol Vis Sci. 2008;49:4712–4720
Crossref

Edelhauser HF, Rowe-Rendleman C, Robinson M et al. Ophthalmic Drug Delivery Systems for the Treatment of Retinal Diseases: Basic Research to Clinical Applications. Investigative Ophthalmology & Visual Science. 2010;51(11):5403–5420.
Crossref

Ericson LA, Rosengren BH. Present therapeutic resources in retinoblastoma. Acta Ophthalmol. 1961;39:569–576.
Crossref

Frederici TJ. Intravitreal injections: AAO’s Focal Points. Clinical Modules for Ophthalmologists. 2009;27(8, module 2):1–12.

Gallie B, Budning A, DeBoer G et al. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. //Arch Ophthalmol. Nov 1996;114(11):1321–1328. 
Crossref

Gallie B, Gronsdahl P, Dimaras H et al. National Retinoblastoma Strategy Canadian Guidelines for Care. Can J Ophthalmol. 2009;44, Suppl. 2:S9
Crossref

Ghassemi F, Shields C. Intravitreal melphalan for refractory or recurrent vitreous seeding from retinoblastoma. Arch Ophthalmol. 2012;130:1268–1271.

Ghate D, Edelahauser HF. Ocular drug delivery. Expert Opin Drug Deliv. 2006;3:275–287.

Gobin Y, Dunkel J, Marr BP. Combined, Sequential Intravenous and Intra-Arterial Chemotherapy (Bridge Chemotherapy) for Young Infants with Retinoblastoma.PLOS ONE www.plosone.org. 2012; 7(9).

Gombos D, Hungerford J, Abramson D et al. Secondary acute myelogenousleukemia in patients with retinoblastoma: is chemotherapy a factor? Ophthalmology. Jul 2007;114(7):1378–1383.

Inomata M, Kaneko A. Chemosensitivity profiles of primary and cultured retinoblastoma cells in a human tumor clonogenic assay. Jpn J Cancer Res. 1987;78: 858–868.

Jager RD, Aiello LP, Patel SC, Cunningham ET. Risks of intravitreous injection: a comprehensive review. Retina. 2004, 24: 676–698

Kaneko A, Suzuki S. Eye-Preservation Treatment of Retinoblastoma with Vitreous Seeding. Japanese Journal of Clinical Oncology. 2003; 33: 601–607.

Kim SH, Lutz RJ, Wang NS, Robinson MR. Transport barriers in transscleral drug delivery for retinal diseases. Ophthalmic Res.2007;39:244–254.

Kivel? T, Eskelin S, Paloheimo M. Intravitreal methotrexate for retinoblastoma. Ophthalmology. 2011;118(8). — P. 1689.

Lambert M, Shields C, Meadows A. A retrospective review of hearing in children with retinoblastoma treated with carboplatin-based chemotherapy. Pediatr Blood Cancer 2008;50:223– 6.

Le Goff MM, Bishop PN. Adult vitreous structure and postnatal changes. Eye. 2008;22:1214–1222.

Munier FL, Gaillard MC, Balmer A, Beck-Popovic M. Intravitreal chemotherapy for vitreous seeding in retinoblastoma: Recent advances and perspectives. Saudi Journal of Ophthalmology. 2013; 27:147–150.

Munier FL, Gaillard MC, Soliman S et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications. Br J Ophthalmol. 2012;96(8):1078–1083. 

Munier FL, Soliman S, Moulin A et al. Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilization of the needle track. Br J Ophthalmol. 2012; 96(8):1084–1086. 

Murphree A, Villablanca J, Deegan W et al. Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Arch Ophthalmol. 1996;114:1348–56. 

Rizzuti A, Dunkel I, Abramson D. The adverse events of chemotherapy for retinoblastoma: what are they? Do we know? Arch Ophthalmol 2008;126:862–5. 

Rodriguez-Galindo C, Chantada GL, Haik BG, Wilson MW. Treatment of retinoblastoma: current status and future perspectives. Curr Treat Options Neurol. 2007 Jul;9(4):294–307.

Rodriguez-Galindo C, Wilson M, Haik B et al. Treatment of intraocular retinoblastoma with vincristine and carboplatin. J Clin Oncol 2003;21:2019–25.

Seregard S, Kock B, Trampe E. Intravitreal chemotherapy for recurrent retinoblastoma in an only eye. Br J Ophthalmol. 1995;79:194–195.

Shah N, Pham D, Murray Tet al. Intravitreal and Subconjunctival Melphalan for Retinoblastoma in Transgenic Mice. Journal of Ophthalmology. 2014;1–9. 

Shields C, De Potter P, Himelstein B et al. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol 1996;114:1330–8.

Shields C, Fulco E, Arias J et al. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Eye. 2013; 27(2): 253–264.

Shields C, Mashayekhi A, Cater J et al. Macular Retinoblastoma Managed With Chemoreduction. Analysis of Tumor Control With or Without Adjuvant Thermotherapy in 68 Tumors. Arch Ophthalmol. 2005;123:765–773

Smith MA, Rubinstein L, Anderson JR, et al. Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxins. J Clin Oncol 1999;17:569–77

Smith SJ, Pulido JS, Salom?o DR et al. Combined intravitreal and subconjunctival carboplatin for retinoblastoma with vitreous seeds // Br J Ophthalmol. 2012;96(8):1073–1077.

Smith SJ, Smith BD. Evaluating the risk of extraocular tumour spread following intravitreal injection therapy for retinoblastoma: a systematic review. Br J Ophthalmol. 2013 Oct;97(10):1231–6. 

Smith SJ, Smith BD, Mohney BG. Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review. Br J Ophthalmol. 2014 Mar; 98(3):292–7.

Suzuki S, Kaneko A. Management of intraocular retinoblastoma and ocular prognosis. Int J Clin Oncol. 2004 Feb;9(1):1–6.

Ueda M, Tanabe J, Inomata M et al. Study on conservative treatment of retinoblastoma — effect of intravitreal injection of melphalan on the rabbit retina. Nihon Ganka Gakkai Zasshi. 1995; 99(11):1230–1235.

Wilson MW, Rodriguez-Galindo C, Haik BG, et al: Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma. Ophthalmology 108:2106–2115, 2001

Yamane T, Kaneko A, Mohri M. The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma. //Int J Clin Oncol. 2004 Apr;9(2):69–73.