Subconjunctival carboplatin in retinoblastoma: Impact of tumor burden and dose schedule

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.