Anecortave acetate as single and adjuvant therapy in the treatment of retinal tumors of LH(BETA)T(AG) mice.
OBJECTIVE
To evaluate the tumor control efficacy of the antiangiogenic agent anecortave acetate as single and combined therapy, in retinal tumor reduction using the LH(BETA)T(AG) mouse model of retinoblastoma.


METHODS
Group A: Ten-week-old, LH(BETA)T(AG) mice received a single subconjunctival injection of anecortave acetate (1200, 600, 300, and 150 microg) delivered to right eyes only. Group B: Ten-week-old, LH(BETA)T(AG) mice received a single subconjunctival injection of anecortave acetate (600, 300, and 150 microg) 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 microg. 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 microg) 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.
Jockovich
Maria-Elena
ME
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, Florida 33101, USA.
Murray
Timothy G
TG
Escalona-Benz
Erika
E
Hernandez
Eleut
E
Feuer
William
W
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007267:Injections; D051379:Mice; D008822:Mice, Transgenic; D011244:Pregnadienediols / Q000627:therapeutic use*; D019572:Retinal Neoplasms / Q000188:drug therapy*; D012175:Retinoblastoma / Q000188:drug therapy*
D000970:Antineoplastic Agents; D011244:Pregnadienediols; D016190:Carboplatin; C418047:anecortave acetate