Evaluation of intravitreal topotecan dose levels, toxicity and efficacy for retinoblastoma vitreous seeds: a preclinical and clinical study.
animal models
efficacy
intravitreal chemotherapy
pharmacokinetics
retinoblastoma
topotecan
toxicity
vitreous seeds
Journal
The British journal of ophthalmology
ISSN: 1468-2079
Titre abrégé: Br J Ophthalmol
Pays: England
ID NLM: 0421041
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
03
12
2020
revised:
09
04
2021
accepted:
13
04
2021
pubmed:
12
5
2021
medline:
23
4
2022
entrez:
11
5
2021
Statut:
ppublish
Résumé
Current melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in our rabbit model and patient cohort. Rabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction. retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan. Intravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC Taken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.
Sections du résumé
BACKGROUND
Current melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in our rabbit model and patient cohort.
METHODS
Rabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction.
PATIENTS
retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan.
RESULTS
Intravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC
CONCLUSIONS
Taken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.
Identifiants
pubmed: 33972235
pii: bjophthalmol-2020-318529
doi: 10.1136/bjophthalmol-2020-318529
pmc: PMC8788260
doi:
Substances chimiques
Antineoplastic Agents, Alkylating
0
Topotecan
7M7YKX2N15
Melphalan
Q41OR9510P
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
288-296Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Organisme : BLRD VA
ID : IK6 BX005225
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : NEI NIH HHS
ID : K08 EY027464
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103391
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: ABD and DLF have a patent with Vanderbilt University Medical Center. ABD has received research funding from Spectrum Pharmaceuticals (now Acrotech Biopharma) through an investigator-initiated study separate from the data presented in this manuscript. None of the other authors has any conflicts of interest or financial disclosures.
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