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Impact of Tumor Burden and Dose Schedule

Brandy H. Hayden, BS; Timothy G. Murray, MD; Ingrid U. Scott, MD, MPH; Nicole Cicciarelli; Eleut Hernandez; William Feuer, MS; Lilia Fulton, BS; Joan M. O'Brien, MD

Arch Ophthalmol. 2000;118:1549-1554.

Objective  To evaluate the impact of tumor burden and chemotherapy dose scheduling on the response to subconjunctival carboplatin treatment in a murine transgenic retinoblastoma model.

Methods  Eighty simian virus 40 T antigen–positive mice were treated at age 5 or 10 weeks. Six control animals received placebo treatment. Twenty-four 5-week-old mice received 6 subconjunctival carboplatin injections at doses of 30 to 300 µg delivered at 72-hour intervals. Fifty 10-week-old mice received either 6 or 12 subconjunctival carboplatin injections at doses of 30 to 300 µg delivered at 72-hour intervals. All eyes were obtained at age 16 weeks for histopathologic examination. Eyes were graded as positive if any tumor was present.

Results  All simian virus 40 T antigen–positive control eyes contained large tumor foci throughout the retina. Subconjunctival carboplatin injections controlled tumors in a dose-dependent manner. Tumor control was observed in 50% of treated eyes at 138.3 µg for the 10-week-old 6-injection group, 94.3 µg for the 5-week-old 6-injection group, and 85.9 µg for the 10-week-old 12-injection group.

Conclusion  Increased tumor burden requires an increase in subconjunctival carboplatin dose scheduling to maintain local tumor control in this murine model of retinoblastoma.

Clinical Relevance  This study documents the efficacy of subconjunctival carboplatin in the treatment of an animal model of retinoblastoma. These data establish a framework for further human clinical trials.

From the Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, Fla (Mss Hayden and Cicciarelli; Drs Murray and Scott; and Messrs Hernandez and Feuer), and the Department of Ophthalmology, University of California, San Francisco (Ms Fulton and Dr O'Brien).

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