Pharmacokinetics and safety profile of oxaliplatin.
In early clinical trials, oxaliplatin has demonstrated significant activity against colorectal cancer, both as a single agent and in combination with 5-fluorouracil (5-FU) and folinic acid (FA). Oxaliplatin differs from cisplatin in its lack of nephrotoxicity and from carboplatin in its hematologic toxicity being mild. The most constant acute side effect of oxaliplatin observed in clinical trials was a transient peripheral neuropathy manifesting as paresthesia and dysesthesia in the extremities, triggered or enhanced by exposure to cold. The neurosensory phenomena, dependent on the cumulative dose of oxaliplatin, affect all patients who receive doses > or = 540 mg/m2 over four cycles or more of therapy. This neurologic toxicity is also highly reversible, with 82% of patients having their neuropathy regress within 4 to 6 months and 41% experiencing complete recovery within 6 to 8 months. With these considerations in mind, the currently recommended dosing schedules for oxaliplatin are 130 mg/m2/d as a 2- to 6-hour infusion or 175 mg/m2/d as a chronomodulated infusion over 5 days, both of which are administered every 3 weeks. Oxaliplatin rapidly disappears from the plasma and is rapidly transformed into putative active species. 5-Fluorouracil and folinic acid, often used in combination with oxaliplatin, do not affect its pharmacokinetics. The favorable pharmacokinetics and safety profile of oxaliplatin contribute to its tolerability, particularly in pretreated cancer patients with reduced renal function. The reversible nature of its dose-limiting neurotoxicity and its synergistic action with 5-FU/FA make oxaliplatin an interesting agent for the treatment of colorectal cancer and for other potential indications.
Extra
J M
JM
Institut Curie, Paris, France.
Marty
M
M
Brienza
S
S
Misset
J L
JL
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001711:Biotransformation; D017321:Clinical Trials, Phase I as Topic; D004357:Drug Synergism; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin