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Review
Cellular and Molecular Pharmacology of Oxaliplatin1
Department of Medicine, Institute Gustave-Roussy, 94805 Villejuif, cedex, France [E. R., S. F.]; Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7260 [S. C.]; Department of Radiation Oncology, Cancer Therapy and Research Center, Institute for Drug Development, and University of Texas Health Science Center, San Antonio, Texas 78245-3217 [J. W.]; Service des Maladies Sanguines Immunitaires et Tumorales, Hôpital Saint-Louis, Paris 12ème, France [E. C.]
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.
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