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P Chevez-Barrios, M Chintagumpala, M Boniuk, MY Hurwitz, RL Hurwitz; Gene Therapy for Retinoblastoma: Report of a Pilot Clinical Study . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2895.
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Purpose: To test the safety and possible efficacy of using intravitreal and intratumoral injections of adenoviral vectors to deliver the herpes thymidine kinase gene (AdV/TK) followed by ganciclovir to treat refractory retinoblastoma in children. Methods: A RAC, IRB, and FDA approved phase I intra-patient dose-escalation clinical trial was established. Patient eligibility was restricted to children with bilateral retinoblastoma who had lost one eye to advanced disease and had failed all standard attempts to save the remaining eye. The first patient received a single injection of 108 v.p. AdV/TK and the next 3 patients received an initial injection of 109 v.p. followed by either one or 2 injections of 1010 v.p. Each injection was followed by 7 days of intravenous ganciclovir. Results: None of the patients experienced dose-limiting toxicity. The three patients who received 1010 v.p. experienced mild intraocular inflammatory responses that were well controlled with steroid administration. Three patients were enucleated because of advancing disease. One patient has had a complete response and is tumor free with excellent vision 7 months following the completion of therapy. The patients who were enucleated all exhibited tumor necrosis around the injection sites and no viable tumor cells were observed anywhere along the needle track. The patients all had marked decrease in the number of vitreal seeds. Two patients received intratumoral injections of AdV/TK and both exhibited tumor necrosis. All of the patients are currently in excellent health with no toxicity from their therapy. Conclusion: AdV/TK followed by ganciclovir can be safely administered to children with retinoblastoma. Early experience suggests that this form of therapy may have a role in the treatment of retinoblastoma. Based on these early results, permission from the RAC, IRB, and FDA has been received to expand the trial to all retinoblastoma patients who are facing enucleation regardless of previous therapy.
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