New developments and approaches in the platinum arena.
Following the introduction of cisplatin and the demonstration of its importance in the treatment of testicular and ovarian cancer, there was a need to develop less toxic analogues. Compared with cisplatin, carboplatin proved markedly less toxic to the kidneys and nervous system and caused less nausea and vomiting, while generally (and certainly for ovarian cancer) retaining equivalent antitumour activity. In many situations, carboplatin is now the drug of choice in view of the improved quality of life it offers patients. Many drug combinations involving platinum complexes have been explored, but those with taxanes are particularly noteworthy. Paclitaxel in combination with a platinum agent is now accepted as a standard component of first-line treatment for ovarian cancer, and produces improved survival. Preclinical studies suggested that drugs containing the diaminocyclohexane ligand would be capable of overcoming intrinsic or acquired resistance. However, this outcome was not realised in the clinic until the development of oxaliplatin, which appears to have a different spectrum of activity compared with cisplatin and carboplatin. Oxaliplatin improves the response rate and progression-free survival when given with fluorouracil for the treatment of advanced colorectal cancer, and its activity in other tumour types is under investigation. ZD0473 is a platinum analogue that relies on steric hindrance to overcome thiol-mediated detoxification. It has a good tolerability profile, is currently undergoing phase II testing, and its activity in combination with other agents is being explored. The trinuclear platinum complex BBR3464 also looks promising in preclinical studies and will shortly be evaluated in phase II trials. Although much research remains to be done, these new developments in platinum-based chemotherapy should translate into significant improvements in treatment for patients with a broad range of tumour types.
Judson
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CRC Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, England.
Kelland
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LR
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000627:therapeutic use*; D016190:Carboplatin / Q000737:chemistry / Q000627:therapeutic use; D002945:Cisplatin / Q000737:chemistry / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013736:Testicular Neoplasms / Q000188:drug therapy*
D009944:Organoplatinum Compounds; C110525:amminedichloro(2-methylpyridine)platinum(II); D016190:Carboplatin; C114062:BBR 3464; D002945:Cisplatin