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Anecortave Acetate as Single and Adjuvant Therapy in the Treatment of Retinal Tumors of LH_BETAT_AG Mice

From the Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, Florida.

PURPOSE. To evaluate the tumor control efficacy of the antiangiogenic agent anecortave acetate as single and combined therapy, in retinal tumor reduction using the LH_BETAT_AG mouse model of retinoblastoma.

METHODS. Group A: Ten-week-old, LH_BETAT_AG mice received a single subconjunctival injection of anecortave acetate (1200, 600, 300, and 150 µg) delivered to right eyes only. Group B: Ten-week-old, LH_BETAT_AG mice received a single subconjunctival injection of anecortave acetate (600, 300, and 150 µg) delivered to right eyes only, either during a cycle of carboplatin (six subconjunctival deliveries) or after the completed cycle. Carboplatin was delivered at the subtherapeutic concentration of 62.5 µg. All animals were euthanatized at 16 weeks of age, and the eyes were examined histopathologically.

RESULTS. A statistically significant reduction in tumor burden was detected after a single periocular injection of anecortave acetate. The reduction of tumor burden followed a U-shaped dose–response curve. Tumor burden was significantly decreased when anecortave acetate and carboplatin were combined. However, varying doses and delivery schedule of these agents had significant impact on the effectiveness of the combined treatment. The most effective scheme was delivering a low dose (150–300 µg) of anecortave acetate after a complete cycle of carboplatin. Histopathological evaluation showed no signs of retinal toxicity to anecortave acetate delivery alone or in combination with carboplatin.

CONCLUSIONS. Anecortave acetate, as monotherapy or as adjuvant therapy, significantly controlled tumor burden in a murine model of retinoblastoma. Moreover, adjuvant therapy enabled the use of typically subtherapeutic carboplatin doses without decreasing efficacy of the therapy.

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