1 INTRODUCTION Preclinical studies demonstrate anti-tumor activity by cardiac glycosides in vitro and in vivo, includ- ing in retinoblastoma. 1 While retrospective studies demonstrate decreased deaths and less tumor pro- liferation in cancer patients on digoxin for cardiac indications, 2,3 there are no reports showing the efi- cacy of digoxin for cancer. Here, we report a case of intra-arterial and systemic digoxin therapy for retinoblastoma. CASE REPORT A 4-year old boy with stage Vb retinoblastoma (inter- national classiication group E) of the right eye pre- sented after incomplete response to three cycles of intra-arterial melphalan chemotherapy administered elsewhere 7 weeks, 4 weeks, and 3 days prior to pre- sentation. Fundus examination revealed a solitary, cream-colored, 12x6mm tumor with type III regres- sion, a retinal detachment, and extensive, non-calciied vitreous seeds (Figure 1A). Given the administration of intra-arterial melphalan just days before, the decision was made to wait 3 weeks to assess for a response. Three weeks later, there was no regression on the main tumor or vitreous seeds, and after consideration Ophthalmic Genetics, 1–4, Early Online, 2011 Copyright © 2011 Informa Healthcare USA, Inc. ISSN: 1381-6810 print/ 1744-5094 online DOI: 10.3109/13816810.2010.544530 ORIGINAL ARTICLE Intra-arterial and Oral Digoxin Therapy for Retinoblastoma Mrinali Patel 1 , Yannis M. Paulus 1 , Y. Pierre Gobin 2 , Hakim Djaballah 3 , Brian Marr 1 , Ira J. Dunkel 4 , Scott Brodie 5 , Christophe Antczak 3 , Robert Folberg 6 , and David H. Abramson 1 1 Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, USA 2 Divisions of Interventional Neuroradiology, Department of Radiology, Neurosurgery, and Neurology, Weill Cornell Medical College, New York, USA 3 Molecular Pharmacology & Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, USA 4 Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, USA 5 Department of Ophthalmology, Mt. Sinai School of Medicine, New York, USA 6 Departments of Biomedical Sciences, Ophthalmology, and Pathology, Oakland University William Beaumont School of Medicine, Rochester, Minnesota, USA ABSTRACT Purpose: Preclinical studies demonstrate that cardiac glycosides such as ouabain and digoxin have antitumor effects on retinoblastoma cells in vitro and in a xenograft murine model of retinoblastoma. Methods: Based on these indings, we report a case of intra-arterial followed by systemic oral digoxin therapy in a patient with unilateral retinoblastoma that had failed prior intra-arterial chemotherapy. Results: Oral administration of digoxin produced no effect, while intra-arterial digoxin therapy produced a modest but measurable response that was likely limited by the inability to achieve sustained drug concentration in the eye. Conclusions: This case highlights both the potential promise and limitations of cardiac glycoside therapy in retinoblastoma. KEYWORDS: intra-arterial; digoxin; cardiac glycosides; retinoblastoma Received 16 June 2010; revised 25 November 2010; accepted 27 November 2010 Correspondence: David H. Abramson, M.D. 70 East 66 th Street, New York, NY 10065. E-mail: abramsod@mskcc.org Ophthalmic Genet Downloaded from informahealthcare.com by Memorial Sloan-Kettering Cancer Center on 03/29/11 For personal use only.