Efficacy of new ruthenium complexes against chemically induced autochthonous colorectal carcinoma in rats.

SD rats bearing acetoxymethylmethylnitrosamine-induced colorectal carcinomas were treated by i.v. administration of trans-imidazolium-bisimidazoletetrachlororuthenate (III) ImH(RuIm2Cl4), bisbenzimidazolium-benzimidazolepentachlororuthenate (III) (BzImH)2(RuBzImCl5) and trans-indazolium-bisindazoletetrachlororuthenate (III) In-dH(ruInd2Cl4). The dose levels used were 0.022 mmol/kg body weight administered twice weekly over ten weeks for all compounds and, additionally, 0.015 mmol/kg for ImH(RuIm2Cl4). All compounds caused a tumor growth inhibition exceeding 90%; differences were found with regard to toxicity: ImH(RuIm2Cl4 and (BzImH)2(RuBzImCl5) caused dose-related decreases in body weight and increases in mortality as shown by 21% and 29% body weight loss compared to controls as well as 10% and 45% mortality for the two dosages of the first compound, and 9% body weight loss compared to controls as well as 7% mortality for the latter compound. In contrast, equimolar administration of IndH(RuInd2Cl4) was not related to any symptoms of toxicity as evidenced by 2% body weight gain compared to controls as well as 0% mortality. Since this latter drug obviously showed remarkable activity in a highly resistant type of tumor at negligible toxicity, it certainly deserves special attention.