Paclitaxel in the treatment of retinal tumors of LH beta-Tag murine transgenic model of retinoblastoma.
OBJECTIVE
The purpose of this study was to investigate tumor control efficacy of paclitaxel in the treatment of retinal tumors harbored by the LH beta-Tag murine transgenic model of retinoblastoma.


METHODS
LH beta-Tag-positive mice (n = 5) 10 weeks of age received two 20-microL subconjunctival injections delivered with a 72-hour interval to right eyes only. Paclitaxel was dissolved in 100% dimethyl sulfoxide (DMSO) and delivered at doses of 0.5 mg, 0.25 mg, 0.125 mg, 0.0625 mg, 0.0313 mg, and 0.0152 mg in a 20-microL volume. Control mice received two subconjunctival injections of DMSO or of saline solution to right eyes only or they remained untreated. Eyes were analyzed at 16 weeks of age for residual tumor burden, which was measured by gauging the cross-sectional area of largest tumor focus.


RESULTS
Linear regression analysis of tumor burden demonstrates a statistically significant (P < 0.001) dose-response relationship between paclitaxel concentration and tumor size. Transient ocular toxicities were observed after treatment, but most had subsided at the time of analysis, 6 weeks after injection. After histologic assessment, the 0.25-mg paclitaxel dose had effectively reduced tumor burden and was associated with minimal toxicity, including mild conjunctival chemosis and fibrosis, corneal epitheliopathy, and corneal edema.


CONCLUSIONS
Subconjunctival delivery of paclitaxel effectively inhibits intraocular tumor burden in the LH beta-Tag model of retinoblastoma. This treatment modality may represent a novel strategy for the clinical management of retinoblastoma.
Suárez
Fernando
F
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, Florida 33101, USA.
Jockovich
Maria-Elena
ME
Hernandez
Eleut
E
Feuer
William
W
Parel
Jean-Marie
JM
Murray
Timothy G
TG
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D003228:Conjunctiva; D004195:Disease Models, Animal; D015552:Injections, Intralesional; D016014:Linear Models; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D017239:Paclitaxel / Q000494:pharmacology* / Q000633:toxicity; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012175:Retinoblastoma / Q000188:drug therapy* / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D037101:Luteinizing Hormone, beta Subunit; D017239:Paclitaxel