PRECLINICAL ACTIVITY OF TRANS-INDAZOLIUM [TETRACHLOROBISINDAZOLERUTHENATE(III)] (NSC-666158, INDCR, KP-1019) AGAINST TUMOR COLONY-FORMING-UNITS AND HEMATOPOIETIC PROGENITOR CELLS

s-indazolium[tetrachlorobisindazoleruthenate(III)] (KP 1019) is a new heavy metal complex with promising activity against tumour cell lines and in animal models. We studied the antineoplastic effects of KP 1019 (final concentrations: 1, 10, 100 mu g/ml) on in vitro proliferation of clonogenic cells from freshly explanted human tumours in a capillar y soft agar cloning system, and compared the activity of KP 1019 with conventional antineoplastic agents. 53 of 75 specimens (71%) showed ad equate growth in controls. KP 1019 inhibited tumour colony formation i n a concentration-dependent manner in both short- (Ih) and long-term ( 21d) exposure experiments. KP 1019 at 100 mu g/ml with Ih exposure was as active as bleomycin, cisplatin, doxorubicin, etoposide, 5-fluorour acil, methotrexate, mitomycin-C and vinblastine, with only paclitaxel more active than KP 1019 (P=0.002). The antitumour activity of KP 1019 was more pronounced after long-term exposure, indicating the potentia l schedule dependency of KP 1019. Activity was observed against non-sm all cell lung, breast and renal cancer. We conclude that if appropriat e plasma levels can be achieved in patients, KP 1019 may have signific ant clinical activity against a variety of different tumour types. (C) 1997 Elsevier Science Ltd.