CYCLOPLATAM - A NOVEL PLATINUM COMPOUND EXHIBITING A DIFFERENT SPECTRUM OF ANTITUMOR-ACTIVITY TO CISPLATIN

Cycloplatam is a novel platinum compound which has shown anti-tumour a ctivity in murine tumour models. In this study, cycloplatam was found to have anti-tumour activity in vitro and in vivo in human tumour mode ls. In 15 cell lines (mainly ovarian), cycloplatam showed similar cyto toxicity as cisplatin, using the sulphorhodamine B assay. Determinatio n of the resistance factor (IC50 of cisplatin-resistant divided by IC5 0 Of parental cell line) clearly showed lower values for cycloplatam t han for cisplatin. In the parental ovarian cell line CH1 and the cispl atin-resistant CH1cisR model, we observed no cross-resistance of cyclo platam and cisplatin. The in vitro anti-tumour activity was confirmed in human tumour xenografts using the clonogenic assay. Mean IC70 value s of cycloplatam were 0.54 mu g/ml (1.25 mu M) and of cisplatin 0.42 m u g/ml (1.4 mu M), respectively. In the murine subcutaneously implante d ADJ/PC6 plasmacytoma in vivo cycloplatam showed less activity than c isplatin, with a 2-fold smaller therapeutic index than cisplatin. In o varian cancer xenografts cycloplatam was less active than cisplatin. H owever, anti-tumour activity of cycloplatam in lung cancer xenografts was quite different from cisplatin. In LXFS 538, a model moderately se nsitive to cisplatin, a partial remission was observed, but in LXFL 52 9, a cisplatin-sensitive model, cycloplatam was inactive, cycloplatam thus demonstrating a different spectrum of anti-tumour activity. Based on these results, further preclinical investigations with other tumou rs, such as cisplatin-sensitive and -resistant gastric cancer models, are warranted with cycloplatam.