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 x 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 (ClinicalTrials.gov number, NCT00460876).

• Authors: Guillermo L Chantada, Adriana C Fandino, Angel M Carcaboso, Eduardo Lagomarsino, Maria T G de Davila, Myriam R Guitter, Adriana B Rose, Julio Manzitti, Guillermo F Bramuglia, David H Abramson
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 50 Issue 4 Pg. 1492-6 (Apr 2009) ISSN: 1552-5783 [Electronic] United States
• PMID: 18978345 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Topotecan

Topics

• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Area Under Curve
• Child, Preschool
• Chromatography, High Pressure Liquid
• Dose-Response Relationship, Drug
• Eye Enucleation
• Humans
• Magnetic Resonance Imaging
• Maximum Tolerated Dose
• Retinal Neoplasms (diagnosis, drug therapy, metabolism)
• Retinoblastoma (diagnosis, drug therapy, metabolism)
• Tomography, X-Ray Computed
• Topotecan (administration & dosage, adverse effects, pharmacokinetics)