title: Lobaplatin: a new antitumour platinum drug.
abstract: Lobaplatin (D-19466) is a diastereometric mixture of platinum(II) complexes containing a 1,2-bis(aminomethyl)cyclobutane stable ligand and lactic acid as the leaving group. Its antitumour activity results from the formation of DNA-drug adducts, mainly as GG and AG intra-strand cross-links. Lobaplatin influences the expression of the c-myc gene, which is involved in oncogenesis, apoptosis and cell proliferation. Lobaplatin has activity in a wide range of preclinical tumour models and appears to overcome tumour resistance to cisplatin and carboplatin in some of these models. In the body, lobaplatin remains largely intact until removed by glomerular filtration. Exposure of the body to lobaplatin (AUC) correlates with dose, creatinine clearance and the degree of thrombocytopoenia. Phase I clinical trials of three quite different administration schedules found the same dose-limiting toxicity (thrombocytopoenia) and similar maximum tolerated doses (60 mg/m(2) per 3 - 4 weeks). In Phase II trials, lobaplatin showed activity in patients with a variety of tumour types. Many of the patients who responded to lobaplatin may also have responded to cisplatin and carboplatin because they had had no prior chemotherapy or had a prolonged remission after earlier treatment. In conclusion, lobaplatin is a new platinum drug, which overcomes some forms of cisplatin resistance in preclinical tumour models. Several potential clinical applications remain unexplored, such as its use in relapsed testicular cancer and in combination with other cancer chemotherapeutic agents and ionising radiation.
authors: Division of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand. m.mckeage@auckland.ac.nz
authors: M J
authors: MJ
authors: McKeage
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003503:Cyclobutanes / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D003503:Cyclobutanes; D009944:Organoplatinum Compounds; C066228:lobaplatin