Therapeutic effect of the arotinoid Ro 15-0778 on chemically induced rat mammary carcinoma

The arotinoid Ro 15-0778 (temarotene) is a third generation retinoid without a polar end-group. Established, palpable and measurable rat mammary tumours, chemically induced by oral administration of 12 mg/animal 7,12-dimethylbenz[a]anthracene, were treated with Ro 15-0778 as a feed-admix in daily doses of 100 mg/kg for 6 weeks and 200 and 400 mg/kg for 9 weeks. For comparison, tamoxifen (anti-oestrogen) was administered as a feed-admix in doses of 10 and 30 mg/kg/day for 9 weeks. Treatment with Ro 15-0778 resulted in a marked retardation of tumour growth in the groups treated with 100 and 200 mg/kg/day and in partial or even complete tumour regression in the group receiving 400 mg/kg/day. Tamoxifen treatment caused a transient tumour growth inhibition during weeks 1-5 with subsequent re-growth of mammary tumours. Both compounds were generally well tolerated. No signs or symptoms of hypervitaminosis A were noted with Ro 15-0778. One single convulsive attack occurred with 200 mg/kg/day of Ro 15-0778 and 400 mg/kg/day caused occasional convulsions in five out of 11 rats. The present investigation underlines the fact that the arotinoid Ro 15-0778 is not only a chemopreventive agent but also exerts a chemotherapeutic effect on established, chemically induced, mammary carcinomas of the rat.