Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma

Autores
Taich, Paula Juliana; Ceciliano, Alejandro; Buitrago, Emiliano; Sampor, Claudia; Fandiño, Adriana Cristina; Villasante, Francisco Eduardo; Lucena, Evandro; Romero, Livia; Chantada, Guillermo Luis; Schaiquevich, Paula Susana
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: To assess the antitumor activity, toxicity, and plasma pharmacokinetics of the combination of melphalan and topotecan for superselective ophthalmic artery infusion (SSOAI) treatment of children with retinoblastoma. Design: Single-center, prospective, clinical pharmacokinetic study. Participants: Twenty-six patients (27 eyes) with intraocular retinoblastoma. Methods: Patients with an indication for SSOAI received melphalan (3e6 mg) and topotecan (0.5e1 mg; doses calculated by age and weight). Plasma samples were obtained for pharmacokinetic studies, and a population approach via nonlinear mixed effects modeling was used. Safety and efficacy were assessed and compared with historical cohorts of patients treated with melphalan single-agent SSOAI. Main Outcome Measures: Melphalan and topotecan pharmacokinetic parameters and efficacy and safety parameters. Results: Twenty-seven eyes from 26 consecutive patients received 66 cycles of SSOAI melphalan and topotecan in combination. All 5 eyes treated as primary therapy responded to the combination chemotherapy and were preserved. Sixteen of the 22 eyes with relapsed or resistant tumors responded, but 3 of them ultimately underwent enucleation at a median of 8 months (range, 7.9e9.1 months). The incidence of grade III and IV neutropenia was 10.6% and 1.5%, respectively, which was comparable with historical controls of single-agent SSOAI melphalan. No episode of fever neutropenia was observed, and no patient required transfusion of blood products. The large variability in melphalan pharmacokinetics was explained by body weight (P<0.05). Concomitant topotecan administration did not influence melphalan pharmacokinetic parameters. There was no effect of the sequence of melphalan and topotecan administration in plasma pharmacokinetics. Conclusions: A regimen combining melphalan and topotecan for SSOAI treatment of retinoblastoma is active and well tolerated. This combination chemotherapy previously showed synergistic pharmacologic activity, and we herein provide evidence of not increasing the hematologic toxicity compared with single-agent melphalan.
Fil: Taich, Paula Juliana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; Argentina
Fil: Ceciliano, Alejandro. Clínica y Maternidad Suizo Argentina. Servicio de Cardiología-Intervencionismo; Argentina
Fil: Buitrago, Emiliano. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; Argentina
Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Villasante, Francisco Eduardo. Clínica y Maternidad Suizo Argentina. Servicio de Cardiología-Intervencionismo; Argentina
Fil: Lucena, Evandro. Instituto Nacional de Câncer; Brasil
Fil: Romero, Livia. Hospital Oncológico Luis Razzetti. Unidad de Oncología Ocular; Venezuela
Fil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; Argentina
Materia
Retinoblastoma
Pharmacokinetic
Melphalan
Topotecan
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/33662
Acceder
id CONICETDig_cc803d112d32e2de1392a99c5113429c
oai_identifier_str oai:ri.conicet.gov.ar:11336/33662
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with RetinoblastomaTaich, Paula JulianaCeciliano, AlejandroBuitrago, EmilianoSampor, ClaudiaFandiño, Adriana CristinaVillasante, Francisco EduardoLucena, EvandroRomero, LiviaChantada, Guillermo LuisSchaiquevich, Paula SusanaRetinoblastomaPharmacokineticMelphalanTopotecanhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Purpose: To assess the antitumor activity, toxicity, and plasma pharmacokinetics of the combination of melphalan and topotecan for superselective ophthalmic artery infusion (SSOAI) treatment of children with retinoblastoma. Design: Single-center, prospective, clinical pharmacokinetic study. Participants: Twenty-six patients (27 eyes) with intraocular retinoblastoma. Methods: Patients with an indication for SSOAI received melphalan (3e6 mg) and topotecan (0.5e1 mg; doses calculated by age and weight). Plasma samples were obtained for pharmacokinetic studies, and a population approach via nonlinear mixed effects modeling was used. Safety and efficacy were assessed and compared with historical cohorts of patients treated with melphalan single-agent SSOAI. Main Outcome Measures: Melphalan and topotecan pharmacokinetic parameters and efficacy and safety parameters. Results: Twenty-seven eyes from 26 consecutive patients received 66 cycles of SSOAI melphalan and topotecan in combination. All 5 eyes treated as primary therapy responded to the combination chemotherapy and were preserved. Sixteen of the 22 eyes with relapsed or resistant tumors responded, but 3 of them ultimately underwent enucleation at a median of 8 months (range, 7.9e9.1 months). The incidence of grade III and IV neutropenia was 10.6% and 1.5%, respectively, which was comparable with historical controls of single-agent SSOAI melphalan. No episode of fever neutropenia was observed, and no patient required transfusion of blood products. The large variability in melphalan pharmacokinetics was explained by body weight (P<0.05). Concomitant topotecan administration did not influence melphalan pharmacokinetic parameters. There was no effect of the sequence of melphalan and topotecan administration in plasma pharmacokinetics. Conclusions: A regimen combining melphalan and topotecan for SSOAI treatment of retinoblastoma is active and well tolerated. This combination chemotherapy previously showed synergistic pharmacologic activity, and we herein provide evidence of not increasing the hematologic toxicity compared with single-agent melphalan.Fil: Taich, Paula Juliana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; ArgentinaFil: Ceciliano, Alejandro. Clínica y Maternidad Suizo Argentina. Servicio de Cardiología-Intervencionismo; ArgentinaFil: Buitrago, Emiliano. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; ArgentinaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; ArgentinaFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Villasante, Francisco Eduardo. Clínica y Maternidad Suizo Argentina. Servicio de Cardiología-Intervencionismo; ArgentinaFil: Lucena, Evandro. Instituto Nacional de Câncer; BrasilFil: Romero, Livia. Hospital Oncológico Luis Razzetti. Unidad de Oncología Ocular; VenezuelaFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; ArgentinaElsevier2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/33662Taich, Paula Juliana; Ceciliano, Alejandro; Buitrago, Emiliano; Sampor, Claudia; Fandiño, Adriana Cristina; et al.; Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma; Elsevier; Ophthalmology; 121; 4-2014; 889-8970161-6420CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S016164201301052Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ophtha.2013.10.045info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:01Zoai:ri.conicet.gov.ar:11336/33662instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:01.335CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
title Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
spellingShingle Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
Taich, Paula Juliana
Retinoblastoma
Pharmacokinetic
Melphalan
Topotecan
title_short Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
title_full Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
title_fullStr Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
title_full_unstemmed Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
title_sort Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
dc.creator.none.fl_str_mv Taich, Paula Juliana
Ceciliano, Alejandro
Buitrago, Emiliano
Sampor, Claudia
Fandiño, Adriana Cristina
Villasante, Francisco Eduardo
Lucena, Evandro
Romero, Livia
Chantada, Guillermo Luis
Schaiquevich, Paula Susana
author Taich, Paula Juliana
author_facet Taich, Paula Juliana
Ceciliano, Alejandro
Buitrago, Emiliano
Sampor, Claudia
Fandiño, Adriana Cristina
Villasante, Francisco Eduardo
Lucena, Evandro
Romero, Livia
Chantada, Guillermo Luis
Schaiquevich, Paula Susana
author_role author
author2 Ceciliano, Alejandro
Buitrago, Emiliano
Sampor, Claudia
Fandiño, Adriana Cristina
Villasante, Francisco Eduardo
Lucena, Evandro
Romero, Livia
Chantada, Guillermo Luis
Schaiquevich, Paula Susana
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Retinoblastoma
Pharmacokinetic
Melphalan
Topotecan
topic Retinoblastoma
Pharmacokinetic
Melphalan
Topotecan
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose: To assess the antitumor activity, toxicity, and plasma pharmacokinetics of the combination of melphalan and topotecan for superselective ophthalmic artery infusion (SSOAI) treatment of children with retinoblastoma. Design: Single-center, prospective, clinical pharmacokinetic study. Participants: Twenty-six patients (27 eyes) with intraocular retinoblastoma. Methods: Patients with an indication for SSOAI received melphalan (3e6 mg) and topotecan (0.5e1 mg; doses calculated by age and weight). Plasma samples were obtained for pharmacokinetic studies, and a population approach via nonlinear mixed effects modeling was used. Safety and efficacy were assessed and compared with historical cohorts of patients treated with melphalan single-agent SSOAI. Main Outcome Measures: Melphalan and topotecan pharmacokinetic parameters and efficacy and safety parameters. Results: Twenty-seven eyes from 26 consecutive patients received 66 cycles of SSOAI melphalan and topotecan in combination. All 5 eyes treated as primary therapy responded to the combination chemotherapy and were preserved. Sixteen of the 22 eyes with relapsed or resistant tumors responded, but 3 of them ultimately underwent enucleation at a median of 8 months (range, 7.9e9.1 months). The incidence of grade III and IV neutropenia was 10.6% and 1.5%, respectively, which was comparable with historical controls of single-agent SSOAI melphalan. No episode of fever neutropenia was observed, and no patient required transfusion of blood products. The large variability in melphalan pharmacokinetics was explained by body weight (P<0.05). Concomitant topotecan administration did not influence melphalan pharmacokinetic parameters. There was no effect of the sequence of melphalan and topotecan administration in plasma pharmacokinetics. Conclusions: A regimen combining melphalan and topotecan for SSOAI treatment of retinoblastoma is active and well tolerated. This combination chemotherapy previously showed synergistic pharmacologic activity, and we herein provide evidence of not increasing the hematologic toxicity compared with single-agent melphalan.
Fil: Taich, Paula Juliana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; Argentina
Fil: Ceciliano, Alejandro. Clínica y Maternidad Suizo Argentina. Servicio de Cardiología-Intervencionismo; Argentina
Fil: Buitrago, Emiliano. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; Argentina
Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Villasante, Francisco Eduardo. Clínica y Maternidad Suizo Argentina. Servicio de Cardiología-Intervencionismo; Argentina
Fil: Lucena, Evandro. Instituto Nacional de Câncer; Brasil
Fil: Romero, Livia. Hospital Oncológico Luis Razzetti. Unidad de Oncología Ocular; Venezuela
Fil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; Argentina
description Purpose: To assess the antitumor activity, toxicity, and plasma pharmacokinetics of the combination of melphalan and topotecan for superselective ophthalmic artery infusion (SSOAI) treatment of children with retinoblastoma. Design: Single-center, prospective, clinical pharmacokinetic study. Participants: Twenty-six patients (27 eyes) with intraocular retinoblastoma. Methods: Patients with an indication for SSOAI received melphalan (3e6 mg) and topotecan (0.5e1 mg; doses calculated by age and weight). Plasma samples were obtained for pharmacokinetic studies, and a population approach via nonlinear mixed effects modeling was used. Safety and efficacy were assessed and compared with historical cohorts of patients treated with melphalan single-agent SSOAI. Main Outcome Measures: Melphalan and topotecan pharmacokinetic parameters and efficacy and safety parameters. Results: Twenty-seven eyes from 26 consecutive patients received 66 cycles of SSOAI melphalan and topotecan in combination. All 5 eyes treated as primary therapy responded to the combination chemotherapy and were preserved. Sixteen of the 22 eyes with relapsed or resistant tumors responded, but 3 of them ultimately underwent enucleation at a median of 8 months (range, 7.9e9.1 months). The incidence of grade III and IV neutropenia was 10.6% and 1.5%, respectively, which was comparable with historical controls of single-agent SSOAI melphalan. No episode of fever neutropenia was observed, and no patient required transfusion of blood products. The large variability in melphalan pharmacokinetics was explained by body weight (P<0.05). Concomitant topotecan administration did not influence melphalan pharmacokinetic parameters. There was no effect of the sequence of melphalan and topotecan administration in plasma pharmacokinetics. Conclusions: A regimen combining melphalan and topotecan for SSOAI treatment of retinoblastoma is active and well tolerated. This combination chemotherapy previously showed synergistic pharmacologic activity, and we herein provide evidence of not increasing the hematologic toxicity compared with single-agent melphalan.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/33662
Taich, Paula Juliana; Ceciliano, Alejandro; Buitrago, Emiliano; Sampor, Claudia; Fandiño, Adriana Cristina; et al.; Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma; Elsevier; Ophthalmology; 121; 4-2014; 889-897
0161-6420
CONICET Digital
CONICET
url http://hdl.handle.net/11336/33662
identifier_str_mv Taich, Paula Juliana; Ceciliano, Alejandro; Buitrago, Emiliano; Sampor, Claudia; Fandiño, Adriana Cristina; et al.; Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma; Elsevier; Ophthalmology; 121; 4-2014; 889-897
0161-6420
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S016164201301052X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ophtha.2013.10.045
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269067305549824
score 13.13397

Publicaciones similares