Subconjunctival carboplatin therapy and cryotherapy in the treatment of transgenic murine retinoblastoma
T. G. Murray, N. Cicciarelli, J. M. O'Brien, E. Hernandez, R. L. Mueller, B. J. Smith and W. Feuer
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Fla, USA.
OBJECTIVES: To determine the efficacy and dose response of subconjunctival
carboplatin with and without cryotherapy in the treatment of murine
transgenic hereditary retinoblastoma. METHODS: Fifty-one 5-week-old
transgenic BLH SV-40 (Charles Rivers Laboratories, Boston, Mass)
T-antigen-positive mice with retinoblastoma were administered 6
subconjunctival injections of carboplatin in 1 eye at drug doses of 10, 15,
20, 25, 62.5, 125, and 250 microg. Six control eyes received 6
subconjunctival injections of balanced salt solution. Fourteen of the 51
subconjunctivally treated eyes received a single application of
transconjunctival cryotherapy immediately prior to each carboplatin
injection. Six control eyes received 6 single applications of
transconjunctival cryotherapy using the above schedule but did not receive
carboplatin. All experimental and control eyes were obtained at 16 weeks of
age for histopathologic examination. RESULTS: A dose-dependent inhibition
of intraocular tumor growth by subconjunctivally delivered carboplatin was
observed in these transgenic retinoblastoma mice. Tumor development was
inhibited in 50% of the mouse eyes at doses of 180 microg. In animals
treated with cryotherapy alone, no tumor control was noted (0 of 6). In
animals treated with subconjunctival carboplatin coupled with cryotherapy,
a tumor control dose of 417 microg was found. No evidence of
histopathologic treatment toxicity was noted. CONCLUSIONS: Subconjunctival
delivery of carboplatin in serial doses effectively inhibits intraocular
tumor growth in a dose-dependent fashion in a transgenic murine
retinoblastoma model. Cryotherapy does not increase tumor control in this
murine retinoblastoma model.
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