Chemotherapeutic Evaluation of Glucarate and N-(4-Hydroxyphenyl)retinamide Alone and in Combination in the Rat Mammary Tumor Model

Abstract

We evaluated calcium glucarate (CGT) and N-(4-hydroxyphenyl)retinamide (HPR) for their effectiveness as antitumor agents. For this evaluation, we tested the effects of CGT and HPR given alone or combined in the diet on the growth of established 7, 12-dimethylbenz[a]anthracene-induced rat mammary tumors. When given alone, optimal doses of CGT (128.0 mmol/kg in the diet) or HPR (2.0 mmol/kg in the diet) administered daily for 25 days reduced mammary tumor sizes by approximately 15% or 20%, respectively. Suboptimal doses of CGT (64.0 mmol/kg) or HPR (0.75 mmol/kg) administered daily for 25 days only slightly inhibited tumor growth; over the 25-day period, the tumor sizes in rats on the CGT diet and in rats on the HPR diet increased by 55% and 70%, respectively, compared with a 98% increase in tumor sizes in the rats on the control diet. In contrast, the combination of suboptimal doses of CGT (64.0 mmol/kg) and HPR (0.75 mmol/kg) administered daily for 25 days decreased tumor sizes by 33%. These results are statistically significant. They show that CGT and HPR act synergistically. Consequently, lower concentrations of these agents can be used to inhibit mammary tumor development and growth. [J Natl Cancer Inst 81:1820–1823, 1989]