title: Preclinical activity of trans-indazolium[tetrachlorobisindazoleruthenate(III)] (NSC 666158; IndCR; KP 1019) against tumour colony-forming units and haematopoietic progenitor cells.
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.
authors.affiliation: Technische Universität München, Klinikum rechts der Isar, Abteilung Hämatologie und Onkologie, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Depenbrock
authors.forename: S
authors.initials: S
authors.lastname: Schmelcher
authors.forename: R
authors.initials: R
authors.lastname: Peter
authors.forename: B K
authors.initials: BK
authors.lastname: Keppler
authors.forename: G
authors.initials: G
authors.lastname: Weirich
authors.forename: T
authors.initials: T
authors.lastname: Block
authors.forename: J
authors.initials: J
authors.lastname: Rastetter
authors.forename: A R
authors.initials: AR
authors.lastname: Hanauske
mesh_terms: D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D009942:Organometallic Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D007191:Indazoles; D009942:Organometallic Compounds; C068847:indazolium-tetrachlorobisindazoleruthenate(III)