Effects of the synthetic vitamin D analogue EB 1089 and tamoxifen on the growth of experimental rat mammary tumours

The anti-tumour effect of EB 1089, a novel vitamin D analogue with reduced calcaemic activity, was examined in vivo using the N-methyl-nitrosourea-induced rat mammary tumour model. The vitamin D compound was given orally at a dose of 1 mu g/kg body weight alone and in combination with tamoxifen (1 mg/kg). Effects were compared with oral tamoxifen treatment alone. EB 1089 significantly inhibited tumour progression compared with controls with a response rate of 58% and a regression rate of 92%. As expected, tamoxifen at the dose given also caused significant inhibition of tumour progression with a response rate of 73%. Combination of these two compounds did not lead to a marked increase in their effectiveness. Histological examination of tumours from EB 1089-treated rats showed a marked reduction in cellularity and mitotic activity. At the dose given, EB 1089 produced a significant rise in serum calcium concentration and urinary calcium excretion. Tamoxifen treatment alone did not significantly alter serum calcium levels. However, combined treatment with tamoxifen and EB 1089 led to a significant reduction in hypercalcaemia compared with EB 1089 alone. It is suggested that vitamin D analogues with reduced calcaemic activity may provide a new therapeutic strategy for certain malignancies, either alone or in combination with established treatment regimens.