A phase I study of periocular topotecan in children with intraocular retinoblastoma Journal Article
| Authors: | Chantada, G. L.; Fandino, A. C.; Carcaboso, A. M.; Lagomarsino, E.; de Davila, M. T. G.; Guitter, M. R.; Rose, A. B.; Manzitti, J.; Bramuglia, G. F.; Abramson, D. H. |
| Article Title: | A phase I study of periocular topotecan in children with intraocular retinoblastoma |
| Abstract: | Purpose: To identify the maximum tolerated dose and dose-limiting toxicity of periocular topotecan in patients with relapsed or resistant intraocular retinoblastoma who are facing imminent enucleation. Methods: For this phase I study, a starting dose of 0.5 mg of periocular topotecan administered through a 25-gauge needle was given with intrapatient escalation at a rate of 0.5 mg/cycle according to toxicity, up to a maximum dose of 2 mg. Two courses separated by 2 weeks were scheduled. Plasma levels of topotecan were measured by high-performance liquid chromatography in patients with available intravenous catheters. Results: Seven eyes of five patients were treated with a total of 14 courses of periocular topotecan. Only mild orbital edema occurred, and grade 1 vomiting developed in the first patient that was controlled with ondansetron for the following courses. Dose-limiting toxicity was not reached and the maximum tolerated dose was set at the target dose of 2 mg (n = 5 eyes). Lactone topotecan systemic exposure was lower than 55 ng/mL · h and it correlated linearly with dose in this small cohort. Even though the study was not designed to assess response, one eye was preserved after a partial response, but the remaining six were enucleated, either after a short period of disease stabilization followed by further therapy with other agents in five patients or by rapidly progressive disease in one. Conclusions: The dose limiting toxicity was not reached. Up to 2 mg of periocular topotecan could be given safely, but further studies are necessary to determine its effect on retinoblastoma. © Association for Research in Vision and Ophthalmology. |
| Keywords: | clinical article; preschool child; child, preschool; clinical trial; area under the curve; dose response; side effect; antineoplastic agents; topotecan; nuclear magnetic resonance imaging; magnetic resonance imaging; antineoplastic agent; metabolism; carboplatin; computer assisted tomography; multiple cycle treatment; neutrophil count; etoposide; nausea; vomiting; tomography, x-ray computed; creatinine; cyclophosphamide; hemoglobin; vincristine; retinoblastoma; retina tumor; dose-response relationship, drug; retinal neoplasms; drug dose escalation; drug fever; alanine aminotransferase; aspartate aminotransferase; radiation dose fractionation; thrombocyte count; ondansetron; enucleation; area under curve; virus infection; external beam radiotherapy; eye disease; blood cell count; drug blood level; eyelid erythema; high performance liquid chromatography; kidney function test; leukocyte count; liver function test; maximum tolerated dose; orbit edema; phase 1 clinical trial; chromatography, high pressure liquid; eye enucleation |
| Journal Title: | Investigative Ophthalmology & Visual Science (IOVS) |
| Volume: | 50 |
| Issue: | 4 |
| ISSN: | 0146-0404 |
| Publisher: | Association for Research in Vision and Ophthalmology |
| Date Published: | 2009-04-01 |
| Start Page: | 1492 |
| End Page: | 1496 |
| Language: | English |
| DOI: | 10.1167/iovs.08-2737 |
| PUBMED: | 18978345 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: IOVSD" - "Source: Scopus" |
