Prevention of skeletal metastasis with the vitamin D analog EB1089: comparison with pamidronate therapy

R. Kremer, MD PhD1 K. El Abdaimi,1 N. Dion,2 V. Papavasiliou,1 P.E. Cardinal,2 L. Binderup,3 D. Goltzman,1 L.G. Ste-Marie2

1Department of Medicine, McGill University, Montreal, Quebec, Canada; 2Universite de Montreal, Montreal, Quebec, Canada; 3Leo Pharmaceutical Products, Ballerup, Denmark

Little progress has been made to date to prevent the development of bone metastasis in various types of cancer and especially breast cancer. The vitamin D analog EB1089 is a potent antiproliferative agent with low calcemic activity. Pamidronate is a strong anti-bone resorbing agent approved for the treatment of established bone metastasis in breast cancer. AIM: To study the effect of EB1089 on the development of bone metastasis and compare it to the bisphosphonate, pamidronate. METHODS: Female balbC nude mice received intra-cardiac injection of 105 human breast cancer cells MDA-MB231 and were implanted simultaneously with alzet osmotic minipumps containing either EB1089 (14 pM/day) or vehicle. Another group of animals was treated with daily administration of either 100 micrograms per day of pamidronate or vehicle. Osteolytic metastases were assessed both radiographically and histologically at timed intervals. RESULTS: Development of bone metastasis was reduce by 50% in mice treated with EB1089 and the total number of metastases was significantly lower in this group (35 vs 11, p<0.001). The mean surface area of osteolytic lesions per animal was significantly reduced with EB1089 (1.4±0.3 vs 0.5±0.2, p<0.05) and mice survived significantly longer (54%±15% vs 89%±10% at 35 days, p<0.07). Animals treated with pamidronate showed similar results. CONCLUSION: These results demonstrate that EB1089 is highly effective in reducing bone metastatic lesions similar to the effect of pamidronate and maybe beneficial alone or in combination in the treatment of breast cancer.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prevention.