Cellular and molecular pharmacology of oxaliplatin.
Oxaliplatin, a diaminocyclohexane-containing platinum, has a spectrum of activity and mechanisms of action and resistance that appear to be different from those of other platinum-containing compounds, notably cisplatin. The first part of this review describes the differences between oxaliplatin and cisplatin in terms of their spectrum of activity and adduct formation and then goes on to discuss molecular and cellular experimental data that potentially explain them. Particular emphasis is placed on the differential role of DNA repair mechanisms. In addition, the anticancer effects of oxaliplatin are optimized when it is administered in combination with other anticancer agents, such as 5-fluorouracil, gemcitabine, cisplatin, or carboplatin; topoisomerase I inhibitors; and taxanes. In vitro and preclinical combination data that could optimize oxaliplatin-based chemotherapy are also reviewed.
Raymond
Eric
E
Department of Medicine, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. raymond@igr.fr
Faivre
Sandrine
S
Chaney
Stephen
S
Woynarowski
Jan
J
Cvitkovic
Esteban
E
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001711:Biotransformation; D018736:DNA Adducts; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin