Ocular pharmacology of topotecan and its activity in retinoblastoma

Authors
Schaiquevich, Paula Susana; Montero Carcaboso, Angel; Buitrago, Emiliano; Taich, Paula Juliana; Opezzo, Javier; Bramuglia, Guillermo Federico; Chantada, Guillermo Luis
Publication Year
2014
Language
English
Format
article
Status
Published version
Description
Purpose: 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. Conclusion: 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.
Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Montero Carcaboso, Angel. Hospital Sant Joan de Déu, Departamento de Oncología; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Buitrago, Emiliano. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Taich, Paula Juliana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Opezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Bramuglia, Guillermo Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Subject
Ocular pharmacokinetics
Retinoblastoma
Topotecan
Vitreous
Medicina Critica y de Emergencia
Medicina Clínica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/36009