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oxaliplatin

Sunday 12 March 2006

Oxaliplatin is a platinum-based chemotherapy drug in the same family as cisplatin and carboplatin. It is typically administered in combination with fluorouracil and leucovorin in a combination known as FOLFOX for the treatment of colorectal cancer.

Compared to cisplatin the two amine groups are replaced by cyclohexyldiamine for improved antitumour activity. The chlorine ligands are replaced by the oxalato bidentate derived from oxalic acid in order to improve water solubility.

Oxaliplatin is marketed by Sanofi-Aventis under the trademark Eloxatin®.

Oxaliplatin belongs to a new class of platinum agent. It contains a platinum atom complexed with oxalate and diaminocyclohexane (DACH).

The bulky DACH is thought to contribute greater cytotoxicity than cisplatin and carboplatin. The exact mechanism of action of oxaliplatin is not known. Oxaliplatin forms reactive platinum complexes which are believed to inhibit DNA synthesis by forming interstrand and intrastrand cross-linking of DNA molecules.

Oxaliplatin is not generally cross-resistant to cisplatin or carboplatin, possibly due to the DACH group and resistance to DNA mismatch repair.

Preclinical studies have shown oxaliplatin to be synergistic with fluorouracil and SN-38, the active metabolite of irinotecan.3 Oxaliplatin is a radiation-sensitizing agent. It is cell-cycle-phase nonspecific.