Purpose Carboplatin administered systemically or periocularly can result in dramatic and prompt regression of retinoblastoma. However, both routes are rarely curative alone and have undesirable side effects. We aimed to assess the efficacy and toxicity of carboplatin +/？ topotecan delivered by ophthalmic artery chemosurgery whereby chemotherapy is infused into the eye via the ophthalmic artery. Methods This retrospective, IRB-approved study investigated retinoblastoma patients whom received carboplatin +/？ topotecan ophthalmic artery chemosurgery. Patient survival, ocular survival, hematologic toxicity, ocular toxicity, second cancer development and electroretinogram response were all evaluated. Results 57 carboplatin +/？ topotecan infusions (of 111 total) were performed in 31 eyes of 24 patients. The remaining infusions were melphalan-containing. All patients were alive and no patient developed a second malignancy at a median follow up of 25 months. The Kaplan-Meier estimate of ocular survival at two years was 89.9% (95% confidence interval [CI], 82.1–97.9%) for all eyes. Grade 3 or 4 neutropenia developed in two patients and one patient developed metastatic disease. By univariate analysis, neither increasing maximum carboplatin/topotecan dose nor cumulative carboplatin/topotecan dose was associated with statistically significant reduction in the electroretinogram responses. Conclusion Carboplatin +/？ topotecan infusions are effective for ophthalmic artery chemosurgery in retinoblastoma: they demonstrate low hematologic and ocular toxicity and no statistically significant influence on electroretinogram responses, and used in conjunction with melphalan-containing OAC, demonstrate excellent patient survival and satisfactory ocular survival.
Doz F, Neuenschwander S, Plantaz D, Courbon B, Gentet JC, et al. (1995) Etoposide and carboplatin in extraocular retinoblastoma: a study by the Société Fran？aise d’Oncologie Pédiatrique. J Clin Oncol 13 902–9.
Abramson DH, Dunkel IJ, Brodie SE, Kim JW, Gobin YP (2008) A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology 115: 1398–1404.
Gobin YP, Dunkel IJ, Marr BP, Francis JH, Brodie SE, et al. (2012) Combined, sequential intravenous and intra-arterial chemotherapy (bridge chemotherapy) for young infants with retinoblastoma. PLoS ONE 7: e44322.
Klufas MA, Gobin YP, Marr B, Brodie SE, Dunkel IJ, et al.. (2012) Intra-Arterial Chemotherapy as a Treatment for Intraocular Retinoblastoma: Alternatives to Direct Ophthalmic Artery Catheterization. AJNR Am J Neuroradiol.
Palioura S, Gobin YP, Brodie SE, Marr BP, Dunkel IJ, et al.. (2012) Ophthalmic artery chemosurgery for the management of retinoblastoma in eyes with extensive (>50%) retinal detachment. Pediatr Blood Cancer.
Calvaruso G, Carabillò M, Giuliano M, Lauricella M, D’Anneo A, et al. (2001) Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: the effect of combined treatment with the topoisomerase I-inhibitor topotecan. Int. J. Oncol. 18: 1233–7.
Pecora Liberman PH, Schultz C, Schmidt Goffi-Gómez MV, Antoneli CBG, Motoro Chojniak M, et al. (2011) Evaluation of ototoxicity in children treated for retinoblastoma: preliminary results of a systematic audiological evaluation. Clin Transl Oncol 13: 348–52.
Schmack I, Hubbard GB, Kang SJ, Aaberg TM Jr, Grossniklaus HE (2006) Ischemic necrosis and atrophy of the optic nerve after periocular carboplatin injection for intraocular retinoblastoma. Am J Ophthalmol 142: 310–315.
Schaiquevich P, Buitrago E, Taich P, Torbidoni A, Ceciliano A, et al. (2012) Pharmacokinetic analysis of melphalan after superselective ophthalmic artery infusion in preclinical models and retinoblastoma patients. Invest Ophthalmol Vis Sci 53: 4205–12.
Van Quill KR, Dioguardi PK, Tong CT, Gilbert JA, Aaberg TM, et al. (2005) Subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma. Ophthalmology 112: 1151–1158.