title: Ocular pharmacology of topotecan and its activity in retinoblastoma.
abstract: OBJECTIVE
  To review the ocular pharmacology and antitumor activity of topotecan for the treatment of retinoblastoma by an evaluation of different routes of administration.
  
  
  METHODS
  Systematic review of studies available at PubMed using the keywords retinoblastoma, topotecan, and camptothecins, including preclinical data such as cell lines and animal models, as well as clinical studies in patients with retinoblastoma.
  
  
  RESULTS
  Forty-two available studies were reviewed. Evidence of antitumor activity against retinoblastoma as a single agent is based on data on cell lines and a limited number of affected patients with intraocular and extraocular disease when given in a protracted schedule. Evidence of additive or synergistic activity in combination with other agents such as carboplatin, melphalan, and vincristine was reported in preclinical and clinical models. In animal models, pharmacokinetic evaluation of topotecan administered by the periocular route shows that most of the drug reaches the vitreous through the systemic circulation. Topotecan administered by intravitreal injection shows high and sustained vitreal concentrations with limited systemic exposure and lack of retinal toxicity at a dose of up to 5 μg. Topotecan administered intraophthalmic artery shows higher passage to the vitreous compared with periocular administration in a swine model.
  
  
  CONCLUSIONS
  Topotecan alone or in combination is active against retinoblastoma. It shows a favorable passage to the vitreous when given intravenously and intraarterially, and ocular toxicity is minimal by all routes of administration. However, its clinical role, optimal dose, and route of administration for the treatment of retinoblastoma are to be determined.
authors.affiliation: *CONICET-Clinical Pharmacokinetics Unit, Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina; †Department of Oncology, Hospital Sant Joan de Deu, Barcelona, Spain; ‡Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina; and §Service of Hematology-Oncology, Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina.
authors.forename: Paula
authors.initials: P
authors.lastname: Schaiquevich
authors.forename: Angel M
authors.initials: AM
authors.lastname: Carcaboso
authors.forename: Emiliano
authors.initials: E
authors.lastname: Buitrago
authors.forename: Paula
authors.initials: P
authors.lastname: Taich
authors.forename: Javier
authors.initials: J
authors.lastname: Opezzo
authors.forename: Guillermo
authors.initials: G
authors.lastname: Bramuglia
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Chantada
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004333:Drug Administration Routes; D006801:Humans; D058449:Intravitreal Injections; D019572:Retinal Neoplasms / Q000188:drug therapy*; D012175:Retinoblastoma / Q000188:drug therapy*; D014018:Tissue Distribution; D059004:Topoisomerase I Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D019772:Topotecan / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D059004:Topoisomerase I Inhibitors; D019772:Topotecan