Background: Studies conducted in recent years have reported promising results regarding the treatment of retinoblastoma with the intra-arterial use of melphalan. In the present study, we intended to report the results of intra-arterial chemotherapy with melphalan (IACT) in the treatment of newly diagnosed or relapsed-refractory retinoblastoma patients at the Department of Pediatric Oncology of Hacettepe University, Ankara, Turkey. Materials and Methods: This was a retrospective study of patients with intraocular retinoblastoma who were treated with IACT from December 2011 to May 2014. A total of 56 eyes of 46 consecutive patients (30 males and 16 females) were included in the study. Forty-four eyes received systemic chemotherapy upon diagnosis (systemic chemotherapy group, SCG), and 12 eyes were those of newly diagnosed patients (primary intra-arterial melphalan group, PIAG). The choice of the IACT dose was based on age. Tumor control and globe salvage with IACT were analyzed. Complete blood counts were examined 7 days after the IACT for systemic toxicity. Ocular toxicities such as proptosis, eyelid edema, ocular motility, and retinal and optic atrophy were assessed by an ocular oncologist with regular ophthalmologic examinations. Results: Enucleation was avoided overall in 66% (37/56) of the eyes, including 75% (9/12) in the PIAG and 64% (28/44) in the SCG patients. The 1-year enucleation-free survival rate was 56.7% at a median follow-up time of 11.9 months (range 0.27-27.6). IACT was administered in a total of 124 cycles (ranging from 1 to 7 cycles, mean 2.3). The responses were as follows: regression of the retinal tumor in 27 eyes and improvements in vitreous seeding in 5 of 15 eyes. The further treatment requirements after IACT were as follows: enucleation in 19 eyes (10 with vitreous seeding), radiotherapy in 3 eyes, systemic chemotherapy in 1 eye, and local therapy in 1 eye. No severe systemic side effects occurred. Transient swelling of the eyelids (22 patients), conjunctival chemosis (12 patients), upper eyelid ptosis (5 patients), redness over the frontal area (3 patients), limitation of ocular motility (3 patients) and mild proptosis (1 patient) were detected. Retinal pigment epithelial alterations (30 patients) and optic atrophy (3 patients) were seen in the late follow-up. Conclusions: Globe salvage and avoidance of radiotherapy may be achieved by IACT with limited toxicity. This treatment is efficient, repeatable and safe.

Kivela T: The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Ophthalmol 2009;93:1129-1131.
Kiss S, Leiderman YI, Mukai S: Diagnosis, classification, and treatment of retinoblastoma. Int Ophthalmol Clin 2008;48:135-147.
Murphree AL: Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin North Am 2005;18:41-53.
Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, Shields JA: The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology 2006;113:2276-2280.
Varan A, Kiratli H, Aydın B, Tarlan B, Poyraz Beyhan Ç, Akyüz C, Büyükpamukçu M: The treatment of retinoblastoma with four-drug regimen including cisplatin, etoposide, vincristine, and cyclophoshamide. Pediatr Hematol Oncol 2012;29:529-537.
Shields CL, De Potter P, Himelstein BP, Shields JA, Meadows AT, Maris JM: Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol 1996;114:1330-1338.
Abramson DH, Dunkel IJ, Brodie SE, Kim JW, Gobin YP: A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology 2008;115:1398-1404.
Gobin YP, Dunkel IJ, Marr BP, Brodie SE, Abramson DH: Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience. Arch Ophthalmol 2011;129:732-737.
Vajzovic LM, Murray TG, Aziz-Sultan MA, Schefler AC, Wolfe SQ, Hess D, Fernandes CE, Dubovy SR: Supraselective intra-arterial chemotherapy: evaluation of treatment-related complications in advanced retinoblastoma. Clin Ophthalmol 2011;5:171-176.
Parareda A, Català J, Carcaboso AM, Sola T, Cruz O, Diaz J, Salvador H, de Torres C, Alvarez-Sampsons A, Sunol M, Vinent J, Guimaraens L, Prat J, Mora J: Intra-arterial chemotherapy for retinoblastoma. Challenges of a prospective study. Acta Ophthalmol 2014;92:209-215.
Shields CL, Manjandavida FP, Lally SE, Pieretti G, Arepalli SA, Caywood EH, Jabbour P, Shields JA: Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma. Ophthalmology 2014;121:1453-1460.
Shields CL, Bianciotto CG, Jabbour P, Ramasubramanian A, Lally SE, Griffin GC, Rosenwasser R, Shields JA: Intra-arterial chemotherapy for retinoblastoma: report No 1, control of retinal tumors, subretinal seeds, and vitreous seeds. Arch Ophthalmol 2011;129:1399-1406.
Suzuki S, Yamane T, Mohri M, Kaneko A: Selective ophthalmic arterial injection therapy for intraocular retinoblastoma: the long-term prognosis. Ophthalmology 2011;118:2081-2087.
Abramson DH, Dunkel IJ, Brodie SE, Marr B, Gobin YP: Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma (chemosurgery). Ophthalmology 2010;117:1623-1629.
Shields CL, Kaliki S, Al-Dahmash S, Rojanaporn D, Leahey A, Griffin G, Jabbour P, Shields JA: Management of advanced retinoblastoma with intravenous chemotherapy then intra-arterial chemotherapy as alternative to enucleation. Retina 2013;33:2103-2109.
Peterson EC, Elhammady MS, Quintero-Wolfe S, Murray TG, Aziz-Sultan MA: Selective ophthalmic artery infusion of chemotherapy for advanced intraocular retinoblastoma: initial experience with 17 tumors. J Neurosurg 2011;114:1603-1608.
Muen WJ, Kingston JE, Robertson F, Brew S, Sagoo MS, Reddy MA: Efficacy and complications of super-selective intra-ophthalmic artery melphalan for the treatment of refractory retinoblastoma. Ophthalmology 2012;119:611-616.
Thampi S, Hetts SW, Cooke DL, Stewart PJ, Robbins E, Banerjee A, Dubois SG, Char D, Halbach V, Matthay K: Superselective intra-arterial melphalan therapy for newly diagnosed and refractory retinoblastoma: results from a single institution. Clin Ophthalmol 2013;7:981-989.
Shields CL, Kaliki S, Shah SU, Bianciotto CG, Liu D, Jabbour P, Griffin GC, Shields JA: Minimal exposure (one or two cycles) of intra-arterial chemotherapy in the management of retinoblastoma. Ophthalmology 2012;119:188-192.
Marr BP, Brodie SE, Dunkel IJ, Gobin YP, Abramson DH: Three-drug intra-arterial chemotherapy using simultaneous carboplatin, topotecan and melphalan for intraocular retinoblastoma: preliminary results. Br J Ophthalmol 2012;96:1300-1303.
Kim J, Do H, Egbert P: Enucleated eyes after failed intra-arterial infusion of chemotherapy for unilateral retinoblastoma: histopathologic evaluation of vitreous seeding. Clin Ophthalmol 2011;5:1655-1658
Abramson DH, Marr BP, Dunkel IJ, Brodie S, Zabor EC, Driscoll SJ, Gobin YP: Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results. Br J Ophthalmol 2012;96:499-502.
Shields CL, Bianciotto CG, Jabbour P, Griffin GC, Ramasubramanian A, Rosenwasser R, Shields JA: Intra-arterial chemotherapy for retinoblastoma: report No 2, treatment complications. Arch Ophthalmol 2011;129:1407-1415.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.