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Low retinal toxicity of intravitreal carboplatin associated with good retinal tumour control in transgenic murine retinoblastoma.

Abstract

BACKGROUND

Retinoblastoma is a rare intraocular malignancy in children. Current treatments have many adverse effects. New therapeutic approaches like intravitreal injections of chemotherapies are currently being developed but their toxicities need to be evaluated on animal models. This study compares the efficacy and toxicity of intravitreal melphalan, topotecan and carboplatin, alone or in combination (sequential administration), in the LHBetaTag retinoblastoma mice.

METHODS

Mice were divided into nine groups: control, carboplatin 1.5 and 4 μg, melphalan 0.1 and 1 μg, topotecan 0.1 and 1 μg, carboplatin 4 μg/topotecan 0.1 μg and melphalan 1 μg/topotecan 0.1 μg. The follow-up was performed using fundus imaging and optical coherence tomography combined with histopathological analysis. Absence of tumour and presence of calcified tumours were the criteria for therapeutic response assessment. Ocular complications were assessed after four weekly injections. Retinal toxicity was defined by the decrease of retinal thickness and of the number of retinal layers.

RESULTS

Topotecan was inactive on retinal tumours. Melphalan (1 μg) led to a complete tumour control in 91.7% of eyes. Carboplatin strongly decreased the tumour burden (85.7-93.8% of eyes without retinal tumour). The intravitreal injection itself led to ocular complications (25% of media opacities and 45.7% of retinal detachment). Only melphalan at 1 μg showed a strong retinal toxicity. The two combinations showed a good efficacy in reducing the number of eyes with retinal tumours with a reduced retinal toxicity.

CONCLUSIONS

This preclinical study suggests that intravitreal injection of carboplatin has a low toxicity and could be evaluated in clinical practice to treat patients suffering from retinoblastoma.

Authors+Show Affiliations

Institut Curie, Research Center, PSL Research University, Chemistry, Modeling and Imaging for Biology (CMIB), University Centre, Orsay, France. INSERM U 1196, CNRS UMR 9187, Paris-Saclay University, Paris-Sud University, University Centre, Orsay, France. Surgical Oncology Department, Ophthalmology Unit, Institut Curie, Hospital Group, Paris, France. Sorbonne Paris Cité, Paris Descartes University, Paris, France.Institut Curie, Research Center, PSL Research University, Chemistry, Modeling and Imaging for Biology (CMIB), University Centre, Orsay, France. INSERM U 1196, CNRS UMR 9187, Paris-Saclay University, Paris-Sud University, University Centre, Orsay, France.Biopathology Department, Institut Curie, Hospital Group, Paris, France.Histology Platform, Institut Curie, Research Center, PSL Research University, Orsay, France.Sorbonne Paris Cité, Paris Descartes University, Paris, France. SIREDO Center (Care, Research and Innovation in Pediatric, Adolescent and Young Adults Oncology), Institut Curie, Hospital Group, Paris, France.Surgical Oncology Department, Ophthalmology Unit, Institut Curie, Hospital Group, Paris, France. Sorbonne Paris Cité, Paris Descartes University, Paris, France.Institut Curie, Research Center, PSL Research University, Chemistry, Modeling and Imaging for Biology (CMIB), University Centre, Orsay, France. INSERM U 1196, CNRS UMR 9187, Paris-Saclay University, Paris-Sud University, University Centre, Orsay, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31872542

Citation

Lemaître, Stéphanie, et al. "Low Retinal Toxicity of Intravitreal Carboplatin Associated With Good Retinal Tumour Control in Transgenic Murine Retinoblastoma." Clinical & Experimental Ophthalmology, 2019.
Lemaître S, Poyer F, Fréneaux P, et al. Low retinal toxicity of intravitreal carboplatin associated with good retinal tumour control in transgenic murine retinoblastoma. Clin Experiment Ophthalmol. 2019.
Lemaître, S., Poyer, F., Fréneaux, P., Leboucher, S., Doz, F., Cassoux, N., & Thomas, C. D. (2019). Low retinal toxicity of intravitreal carboplatin associated with good retinal tumour control in transgenic murine retinoblastoma. Clinical & Experimental Ophthalmology, doi:10.1111/ceo.13711.
Lemaître S, et al. Low Retinal Toxicity of Intravitreal Carboplatin Associated With Good Retinal Tumour Control in Transgenic Murine Retinoblastoma. Clin Experiment Ophthalmol. 2019 Dec 24; PubMed PMID: 31872542.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low retinal toxicity of intravitreal carboplatin associated with good retinal tumour control in transgenic murine retinoblastoma. AU - Lemaître,Stéphanie, AU - Poyer,Florent, AU - Fréneaux,Paul, AU - Leboucher,Sophie, AU - Doz,François, AU - Cassoux,Nathalie, AU - Thomas,Carole D, Y1 - 2019/12/24/ PY - 2019/08/26/received PY - 2019/12/05/revised PY - 2019/12/18/accepted PY - 2019/12/25/pubmed PY - 2019/12/25/medline PY - 2019/12/25/entrez KW - carboplatin KW - fundus imaging and optical coherence tomography KW - intravitreal injection KW - melphalan KW - retinoblastoma KW - topotecan JF - Clinical & experimental ophthalmology JO - Clin. Experiment. Ophthalmol. N2 - BACKGROUND: Retinoblastoma is a rare intraocular malignancy in children. Current treatments have many adverse effects. New therapeutic approaches like intravitreal injections of chemotherapies are currently being developed but their toxicities need to be evaluated on animal models. This study compares the efficacy and toxicity of intravitreal melphalan, topotecan and carboplatin, alone or in combination (sequential administration), in the LHBetaTag retinoblastoma mice. METHODS: Mice were divided into nine groups: control, carboplatin 1.5 and 4 μg, melphalan 0.1 and 1 μg, topotecan 0.1 and 1 μg, carboplatin 4 μg/topotecan 0.1 μg and melphalan 1 μg/topotecan 0.1 μg. The follow-up was performed using fundus imaging and optical coherence tomography combined with histopathological analysis. Absence of tumour and presence of calcified tumours were the criteria for therapeutic response assessment. Ocular complications were assessed after four weekly injections. Retinal toxicity was defined by the decrease of retinal thickness and of the number of retinal layers. RESULTS: Topotecan was inactive on retinal tumours. Melphalan (1 μg) led to a complete tumour control in 91.7% of eyes. Carboplatin strongly decreased the tumour burden (85.7-93.8% of eyes without retinal tumour). The intravitreal injection itself led to ocular complications (25% of media opacities and 45.7% of retinal detachment). Only melphalan at 1 μg showed a strong retinal toxicity. The two combinations showed a good efficacy in reducing the number of eyes with retinal tumours with a reduced retinal toxicity. CONCLUSIONS: This preclinical study suggests that intravitreal injection of carboplatin has a low toxicity and could be evaluated in clinical practice to treat patients suffering from retinoblastoma. SN - 1442-9071 UR - https://www.unboundmedicine.com/medline/citation/31872542/Low_retinal_toxicity_of_intravitreal_carboplatin_associated_with_good_retinal_tumour_control_in_transgenic_murine_retinoblastoma L2 - https://doi.org/10.1111/ceo.13711 DB - PRIME DP - Unbound Medicine ER -