Artículo
Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
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
Fecha de publicación:
04/2014
Editorial:
Elsevier
Revista:
Ophthalmology
ISSN:
0161-6420
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Retinoblastoma
,
Pharmacokinetic
,
Melphalan
,
Topotecan
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Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
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
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