Efficacy and Toxicity of Intravitreous Chemotherapy for Retinoblastoma: Four-Year Experience.

Abstract

PURPOSE:

To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan.

PARTICIPANTS:

A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC).

DESIGN:

Retrospective cohort study.

METHODS:

Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest.

MAIN OUTCOME MEASURES:

Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation.

RESULTS:

There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such that on average each intravitreous melphalan injection was associated with a 5.3-μV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P = 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P = 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity.

CONCLUSIONS:

Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes.

• Authors: Jasmine H Francis, Scott E Brodie, Brian Marr, Emily C Zabor, Ijah Mondesire-Crump, David H Abramson
• Journal: Ophthalmology (Ophthalmology) Vol. 124 Issue 4 Pg. 488-495 (04 2017) ISSN: 1549-4713 [Electronic] United States
• PMID: 28089679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Alkylating
• Topoisomerase I Inhibitors
• Topotecan
• Melphalan

Topics

• Antineoplastic Agents, Alkylating (therapeutic use, toxicity)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Child, Preschool
• Cohort Studies
• Disease-Free Survival
• Electroretinography (drug effects)
• Female
• Humans
• Infant
• Injections, Intraocular
• Intravitreal Injections
• Male
• Melphalan (therapeutic use, toxicity)
• Neoplasm Seeding
• Ophthalmic Artery
• Ophthalmoscopy
• Retina (physiopathology)
• Retinal Neoplasms (drug therapy, pathology)
• Retinoblastoma (drug therapy, pathology)
• Retrospective Studies
• Topoisomerase I Inhibitors (therapeutic use)
• Topotecan (therapeutic use)
• Treatment Outcome
• Vitreous Body (drug effects, pathology)