A phase I study of periocular topotecan in children with intraocular

CHANTADA GL, FANDINO AC, CARCABOSO AM, LAGOMARSINO E, DE DAVILA MT, GUITTER MR, ROSE A, MANZITTI J, BRAMUGLIA G, ABRAMSON DH.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

Año: 2008

0146-0404

Purpose: To identify the maximum tolerated dose and dose limiting toxicity ofperiocular topotecan in patients with relapsed or resistant intraocularretinoblastoma facing imminent enucleation. Methods: For this phase I study, astarting dose of 0.5 mg of periocular topotecan administered through a 25G needlewas given with intra-patient escalation at a rate of 0.5 mg/cycle according totoxicity, up to a maximum dose of 2 mg. Two courses separated by 2 weeks werescheduled. Plasma levels of topotecan were measured by High Performance LiquidChromatography in patients with available intravenous catheters. Results: 7 eyes from 5 patients were treated with a total of 14 courses of periocular topotecan. Only mild orbital edema occurred and grade 1 vomiting developed in the firstpatient that was controlled with ondansetron for the following courses. Doselimiting toxicity was not reached and the maximum tolerated dose was set at thetarget dose of 2 mg (n= 5 eyes). Lactone topotecan systemic exposure was lowerthan 55 ng/ml*hr and it was linearly correlated to dose in this small cohort.Even though the study was not designed to assess response, one eye is stillpreserved after a partial response, but the remaining 6 were enucleated, eitherafter a short period of disease stabilization followed by further therapy withother agents in 5 or rapidly progressive disease in one. Conclusions: The doselimiting toxicity was not reached. Up to 2mg of periocular topotecan could begiven safely but further studies are necessary to determine its activity forretinoblastoma.