Lobaplatin: a new antitumour platinum drug

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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/m2 per 3 - 4 weeks). In Phase II trials, lobaplatin showe...