oxaliplatin

oxaliplatin, platinum-based chemotherapy drug used primarily to treat colorectal cancer. Oxaliplatin often is used in combination with other anticancer drugs, especially 5-fluorouracil (5-FU) and leucovorin. It was discovered in 1976 by Japanese chemist Kidani Yoshinori at Nagoya City University, as part of efforts to develop platinum-based chemotherapy drugs with improved safety and efficacy compared to earlier compounds such as cisplatin. Its introduction in Europe in 1996 and the United States in the early 2000s contributed to significant improvements in survival rates of advanced colorectal cancer patients.

Oxaliplatin is structurally different from earlier platinum compounds, such as cisplatin and carboplatin, and has a distinct mechanism of action; it also is known for containing a unique bulky diaminocyclohexane (DACH) ring in its structure, which affects its cytotoxicity. In particular, the platinum atom of oxaliplatin reacts with molecules in DNA to form disruptive covalent bonds known as cross-links, which result in conformational distortions in DNA strands. Oxaliplatin typically forms these bonds at specific sites on guanine or adenine bases. Intrastrand cross-links (between adjacent guanine or guanine-adenine pairs on the same DNA strand) are the most common and biologically significant. Interstrand cross-links (between guanines on opposite DNA strands) may also occur, though less frequently. Oxaliplatin-induced cross-links distort the DNA helix, causing kinks and thereby preventing the helical structure from properly unwinding, which interferes with cell replication and can lead to cell death.

Oxaliplatin is administered intravenously, commonly as part of a treatment regimen known as FOLFOX, which includes 5-FU and leucovorin. In such combination regimens, oxaliplatin can help to significantly improve overall survival and disease-free survival in colorectal cancer patients, particularly those with stage III (advanced) cancer. Clinical trials indicate that when used together with other agents, the drug can be effective against additional cancers, including gastric, pancreatic, and ovarian cancers, as well as cancers that are resistant to cisplatin and carboplatin.

A significant challenge associated with oxaliplatin is dose-limiting toxicity, especially peripheral sensory neuropathy. This condition can present acutely with transient cold-induced tingling or pain shortly after infusion; it also can develop into a chronic form that persists for months or even becomes permanent. Other side effects can include nausea, vomiting, diarrhea, fatigue, and low blood cell counts.