Oxaliplatin is a platinum-based chemotherapy drug in the same family as cisplatin and carboplatin. Compared to cisplatin the two amine groups are replaced by diamino cyclohexane (DACH) group to provide a greater antitumor effect. However, this leads to poorer water solubility, which was compensated by the addition of the chloride moieties. Due to this chemical moiety, oxaliplatin readily undergoes non-enzymatic biotransformation, thus complicating oxaliplatin's pharmacokinetics. Like most platinum-based compounds, oxaliplatin's mechanism of action is primarily through DNA damage through DNA crosslinking, particularly intrastrand and interstrand crosslinking. However, due to the structure of oxaliplatin, its adducts make the binding of mismatch repair protein to DNA harder compared to cisplatin or carboplatin's adducts, resulting in greater cytotoxic effects. The DACH moiety also prevents cross-resistance with cisplatin and carboplatin.
Although oxaliplatin has been investigated as a monotherapy, it is typically administered in combination with fluorouracil and leucovorin, known as the FOLFOX regimen, for the treatment of colorectal cancer. This is an effective combination treatment both as a first-line treatment and in patients refractory to an initial fluorouracil and leucovorin combination. Ongoing trials have also shown promising results for oxaliplatin use in nonHodgkin’s lymphoma, breast cancer, mesothelioma, and non-small cell lung cancer.
Oxaliplatin was approved by the FDA on January 9, 2004 and is currently marketed by Sanofi-Aventis under the trademark Eloxatin®.
Oxaliplatin, in combination with infusional fluorouracil and leucovorin, is indicated for the treatment of advanced colorectal cancer and adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor.
Inselspital, Bern, Bern, Switzerland
Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, United States
USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles, California, United States
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, Georgia, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood, Illinois, United States
Roswell Park Cancer Institute, Buffalo, New York, United States
Roswell Park Cancer Institute, Buffalo, New York, United States
Case Western Reserve University, Cleveland, Ohio, United States
Hopital Beaujon, Clichy, France
Institut Jules Bordet, Brussels, Belgium
American Hospital of Paris, Neuilly Sur Seine, France
City of Hope, Duarte, California, United States
Case Western Reserve University, Cleveland, Ohio, United States
Kaplan Cancer Center, New York, New York, United States
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