Preclinical activity of trans-indazolium[tetrachlorobisindazoleruthenate(III)] (NSC 666158; IndCR; KP 1019) against tumour colony-forming units and haematopoietic progenitor cells

Eur J Cancer. 1997 Dec;33(14):2404-10. doi: 10.1016/s0959-8049(97)00277-3.

Abstract

Trans-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 micrograms/ml) on in vitro proliferation of clonogenic cells from freshly explanted human tumours in a capillary soft agar cloning system, and compared the activity of KP 1019 with conventional antineoplastic agents. 53 of 75 specimens (71%) showed adequate growth in controls. KP 1019 inhibited tumour colony formation in a concentration-dependent manner in both short- (1 h) and long-term (21 d) exposure experiments. KP 1019 at 100 micrograms/ml with 1 h exposure was as active as bleomycin, cisplatin, doxorubicin, etoposide, 5-fluorouracil, 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 potential schedule dependency of KP 1019. Activity was observed against non-small cell lung, breast and renal cancer. We conclude that if appropriate plasma levels can be achieved in patients, KP 1019 may have significant clinical activity against a variety of different tumour types.

MeSH terms

  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Indazoles / pharmacology*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Organometallic Compounds / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

Substances

  • Indazoles
  • Organometallic Compounds
  • indazolium-tetrachlorobisindazoleruthenate(III)