Broadening the clinical use of platinum drug–based chemotherapy with new analogues

Abstract

The three platinum-containing drugs that have been thus far approved by the FDA – cisplatin, carboplatin and oxaliplatin – have had a significant effect in the treatment of patients with some malignancies such as testicular, ovarian and colorectal cancer. However, much more remains to be achieved to widen the therapeutic use of this important class of drug, either via further analogue development or by judicious use of combining the existing drugs with new molecularly targeted agents. Two analogues arising from an academic (Institute of Cancer Research)/pharmaceutical (Johnson Matthey/AnorMed) collaboration – satraplatin (JM-216) and picoplatin (JM-/AMD-473) – have recently shown promising clinical activity; satraplatin (an orally available drug) in hormone-refractory prostate cancer and picoplatin in small-cell lung cancer. There have also been advances in delivery vehicles for platinum drugs (e.g., the diaminocyclohexane [DACH]-based AP-5346 and aroplatin/liposomal cis-bis-neodecanoato-trans-(R,R)-1,2-diaminocyclohexane platinum (II) [L-NDDP] are in early clinical development). Platinum-based drugs have also been successfully combined with molecularly targeted drugs (e.g., the recent approval of the vascular endothelial growth factor monoclonal antibody bevacizumab with carboplatin and paclitaxel in patients with NSCLC).

Keywords::

• AP-5346
• aroplatin
• bevacizumab
• carboplatin
• cisplatin
• drug combinations
• oxaliplatin
• picoplatin
• platinum
• satraplatin