title: Preclinical activity of a new platinum analogue, lobaplatin, in cisplatin-sensitive and -resistant human testicular, ovarian, and gastric carcinoma cell lines.
abstract: Lobaplatin [1,2-diamminomethylcyclobutane-platinum(II) lactate] is a new platinum compound with interesting preclinical activity and apparently no nephro- or neurotoxicity that is currently undergoing clinical phase II studies. Little is known about the cross-resistance between cisplatin and lobaplatin. The activity of this new compound in comparison with cisplatin and carboplatin was evaluated in cisplatin-sensitive and cisplatin-resistant human testicular, gastric, and ovarian carcinoma cell lines using 96 h continuous drug exposure in a sulforhodamine-B assay. In three cisplatin-sensitive testicular carcinoma cell lines, lobaplatin and cisplatin showed comparable antitumor activity. The 50% growth-inhibitory concentrations (IC50 values) determined for cisplatin ranged from 0.1 to 0.4 microM, and those found for lobaplatin ranged from 0.25 to 0.5 microM. Carboplatin showed markedly lower cytotoxicity in all cell lines tested. Lobaplatin was not cross-resistant to cisplatin in a 10-fold cisplatin-resistant testicular carcinoma cell line and showed only weak cross-resistance in a 20-fold cisplatin-resistant ovarian carcinoma cell line. In contrast, complete cross-resistance between cisplatin and lobaplatin occurred in two cisplatin-resistant human gastric carcinoma cell lines, which were 3.3- and 9-fold resistant to cisplatin and 3.1- and 6.5-fold resistant to lobaplatin, respectively. Furthermore, lobaplatin showed significant activity against cisplatin-resistant human ovarian and testicular carcinoma xenografts in vivo. These data indicate a high level of activity for lobaplatin at clinically achievable concentrations in ug-sensitive testicular, ovarian, and gastric carcinoma cell lines and a lack of complete cross-resistance to cisplatin. Further clinical development of lobaplatin is clearly warranted.
authors.affiliation: West German Cancer Center, Essen.
authors.forename: A
authors.initials: A
authors.lastname: Harstrick
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: M
authors.initials: M
authors.lastname: Scharnofkse
authors.forename: G
authors.initials: G
authors.lastname: Hapke
authors.forename: D
authors.initials: D
authors.lastname: Reile
authors.forename: H J
authors.initials: HJ
authors.lastname: Schmoll
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D003503:Cyclobutanes / Q000494:pharmacology*; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D013274:Stomach Neoplasms / Q000473:pathology*; D013736:Testicular Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003503:Cyclobutanes; D009944:Organoplatinum Compounds; D016190:Carboplatin; C066228:lobaplatin; D002945:Cisplatin