Antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-vitamin D₃ analogue in transgenic mice with retinoblastoma

Objective: To evaluate the in vivo efficacy and clinical toxic effects of the 1,25-dihydroxy-16-ene-23-yne-vitamin D₃ analogue in β-luteinizing hormone-Tag (LHβ-Tag) transgenic mice with heritable retinoblastoma. Methods: Forty-two mice (8-10 weeks old), randomly assigned to experimental (n=21) or control (n=21) groups, received intraperitoneal injections of 0.05 μg of 1,25-dihydroxy-16-ene-23-yne-D₃ in 0.5-mL mineral oil vehicle (experimental group) or 0.5 mL of mineral oil vehicle (control group) for 5 weeks. One experimental and 3 control animals died of injection-related trauma. Eyes were enucleated 1 week after treatment and were examined histologically in a masked fashion. Results: All experimental and control animals showed evidence of tumor. The tumors in the experimental mice showed a significantly smaller cross-sectional area (0.88±0.08 mm²) compared with that in the control mice (1.12±0.12 mm²) (P=.02). All mice completed the treatment and showed no clinical evidence of toxic effects. Conclusions: Tumors in transgenic mice with retinoblastoma treated with 1,25(OH)₂-16- ene-23-yne-D₃ showed a 21% smaller cross sectional area compared with that in the control mice, without producing clinically apparent toxic effects. This compound may be useful as adjunctive therapy in the treatment of retinoblastoma.