title: Intra-arterial chemotherapy is more effective than sequential periocular and intravenous chemotherapy as salvage treatment for relapsed retinoblastoma.
abstract: BACKGROUND
  Treatment of eyes with retinoblastoma failing systemic chemoreduction and external beam radiotherapy is seldom efficacious. This study compares the efficacy and toxicity of intra-arterial ophthalmic artery chemotherapy (IAO) to our historical cohort of sequential periocular and systemic chemotherapy in such patients.
  
  
  METHODS
  Eighteen eyes (15 consecutive patients) were retrospectively evaluated. Eight eyes received IAO for a median of four cycles (range: 2-9) including melphalan alone (n = 3) or after topotecan and carboplatin (n = 4) or topotecan and carboplatin without melphalan (n = 1). Ten eyes received a median of two cycles (range: 1-3) of periocular topotecan (n = 9) or carboplatin (n = 1) followed by intravenous topotecan and cyclophosphamide in three patients if at least stable disease was achieved. Both groups were comparable for disease extension and prior therapy.
  
  
  RESULTS
  No extraocular dissemination or second malignancy occurred and all patients are alive. The probability of enucleation-free eye survival at 12 months was 0.87 (95% CI: 0.42-0.97) for the IAO group, compared to 0.1 (95% CI: 0.06-0.35) for the periocular group (P < 0.01). Ocular toxicity was mild and similar in both groups (mostly mild orbital edema). Systemic toxicity was low for IAO and periocular injection, but children who received sequentially intravenous chemotherapy (n = 12 cycles) had five episodes of grade 4 neutropenia, three of which resulted in hospitalizations. No case in the IAO group presented these complications.
  
  
  CONCLUSIONS
  IAO is significantly superior to sequential periocular-intravenous topotecan-containing regimens in eyes with relapsed intraocular retinoblastoma with a more favorable toxicity profile.
authors.affiliation: CONICET-Clinical Pharmacokinetics Unit, Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina.
authors.forename: Paula
authors.initials: P
authors.lastname: Schaiquevich
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ceciliano
authors.forename: Natalia
authors.initials: N
authors.lastname: Millan
authors.forename: Paula
authors.initials: P
authors.lastname: Taich
authors.forename: Francisco
authors.initials: F
authors.lastname: Villasante
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Fandino
authors.forename: Julieta
authors.initials: J
authors.lastname: Dominguez
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Chantada
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial; D056965:Injections, Intraocular; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009880:Ophthalmic Artery; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012175:Retinoblastoma / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D016879:Salvage Therapy; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014750:Vincristine; D005047:Etoposide; D019772:Topotecan; D008558:Melphalan