Five TNO platinum compounds were evaluated for antitumor activities in two human ovarian carcinoma tumor lines grown in nude mice. The most active drug, TNO-38, was investigated in five additional lines with a known range of sensitivity to cisplatin. None of the new compounds showed superior activity to cisplatin. The slightly lower activity of TNO-38 as compared to the parent compound was reproducible in all tumor lines. Besides the similarity in the antitumor activity, a remarkable correspondence in platinum distribution and retention at 24 hr of TNO-38 and cisplatin could be observed. Chromatographic analysis of the compounds in their injection fluids showed single peaks for TNO-26 and TNO-38. The degradation products of the latter drugs may have affected their activity and toxicity. These human ovarian cancer xenografts may offer a reliable screening model for selection of a cisplatin analog with a higher therapeutic index or without cross-resistance for treatment in ovarian cancer.
A series of eight human ovarian cancer lines grown in nude mice were used to compare the activity of hexamethylmelamine (HMM) and N2,N4,N6-trihydroxy methyl-N2,N4,N6-trimethylmelamine (trimelamol). The tumor lines differed in histological subtype and growth rate. The drugs were administered i.p. at the maximum tolerated dose at alternate days. Differences in volume of treated and control tumors were endpoints of the study. The tumor lines varied widely in sensitivity to HMM and in four lines a T/C% below 25% was achieved. Trimelamol appeared to be more active than HMM and achieved a T/C below 25% in seven tumor lines. Thus far, the drug has demonstrated significant activity in a phase I trial in ovarian cancer patients. Comparative clinical studies of HMM vs trimelamol have not yet been performed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.