Clinical pharmacokinetics and administration of established platinum drugs.
We review the pharmacology and clinical administration of the commonly used platinum-based anticancer drugs cisplatin and carboplatin, and the more recently approved diamminocyclohexane-based oxaliplatin. The development of analogues of cisplatin has been focused upon identifying compounds with less toxicity and with a different spectrum of activity. Carboplatin exemplifies the former, while the initial data with oxaliplatin support its activity in cisplatin-resistant tumours. The clinical pharmacokinetics of the drugs are reviewed. Incorporation of these data into the design of clinical regimens has permitted individualised therapy with carboplatin, and has enhanced safety. Additional investigation of the pharmacodynamics of all of these agents is expected to result in their selective application. The clinical effects of these analogues are discussed.
O'Dwyer
P J
PJ
University of Pennsylvania Cancer Center, Philadelphia, USA.
Stevenson
J P
JP
Johnson
S W
SW
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin