title: Efficacy and Toxicity of Intravitreous Chemotherapy for Retinoblastoma: Four-Year Experience.
abstract: To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan.
  
  
  
  A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC).
  
  
  
  Retrospective cohort study.
  
  
  
  Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest.
  
  
  
  Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation.
  
  
  
  There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such that on average each intravitreous melphalan injection was associated with a 5.3-μV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P = 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P = 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity.
  
  
  
  Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes.
authors.affiliation: Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill-Cornell Medical Center, New York, New York. Electronic address: francij1@mskcc.org.
authors.forename: Jasmine H
authors.initials: JH
authors.lastname: Francis
authors.affiliation: Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Brodie
authors.affiliation: Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill-Cornell Medical Center, New York, New York.
authors.forename: Brian
authors.initials: B
authors.lastname: Marr
authors.affiliation: Department of Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Zabor
authors.affiliation: Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Ijah
authors.initials: I
authors.lastname: Mondesire-Crump
authors.affiliation: Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill-Cornell Medical Center, New York, New York.
authors.forename: David H
authors.initials: DH
authors.lastname: Abramson
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D004596:Electroretinography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007223:Infant; D056965:Injections, Intraocular; D058449:Intravitreal Injections; D008297:Male; D008558:Melphalan / Q000627:therapeutic use / Q000633:toxicity*; D009366:Neoplasm Seeding; D009880:Ophthalmic Artery; D009887:Ophthalmoscopy; D012160:Retina / Q000503:physiopathology; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012175:Retinoblastoma / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D059004:Topoisomerase I Inhibitors / Q000627:therapeutic use; D019772:Topotecan / Q000627:therapeutic use; D016896:Treatment Outcome; D014822:Vitreous Body / Q000187:drug effects* / Q000473:pathology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; D008558:Melphalan