Oxaliplatin

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 ammine 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®.

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Mechanism of action and efficacy

The exact mechanism of action of oxaliplatin is not known.^{[citation needed]} In vivo studies showed oxaliplatin has anti-tumor activity against colon carcinoma through its (non-targeted) cytotoxic effects. Median patient survival is approximately 5 months greater compared to the previous standard treatment.

Side-effects

Side-effects of oxaliplatin treatment can potentially include:

• Neuropathy, (both an acute, reversible sensitivity to cold and numbness in the hands and feet and a chronic, possibly irreversible foot/leg, hand/arm numbness, often with deficits in proprioception)^[2]
• Fatigue
• Nausea, vomiting, and/or diarrhea
• Neutropenia
• Ototoxicity (hearing loss)

In addition, some patients may experience an allergic reaction to platinum-containing drugs.

Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin.^[2]

History

Oxaliplatin was discovered in 1976 at Nagoya City University in Japan by Professor Yoshinori Kidani, who was granted U.S. Patent 4,169,846 over the drug in 1979. Oxaliplatin was subsequently in-licensed by Debiopharm, a Swiss drug company headquartered in Lausanne and developed as an advanced colorectal cancer treatment. Debio licensed the drug to Sanofi-Aventis in 1994. Eloxatin gained European approval in 1999 and FDA approval in 2004.

Patent information

Eloxatin is covered by patent numbers 5338874 (Expiry Apr 07,2013), 5420319 (Expiry Aug 08,2016), 5716988 (Expiry Aug 07,2015) and 5290961 (Expiry Jan 12, 2013) (see Electronic Orange Book patent info for Eloxatin).^[3] Exclusivity code I-441, which expires on Nov 04, 2007, is for use combination with infusional 5-FU/LV for adjuvant treatment stage III colon cancer patients who have undergone complete resection primary tumor-based on improvement in disease free survival with no demonstrated benefit overall survival after 4 years. Exclusivity code NCE, New Chemical Entity, expires on Aug 09, 2007.^[3]

References

1. ^ Ehrsson H, Wallin I, Yachnin J. Medical Oncology. 2002; 19:251-265.
2. ^ ^{a b} Pasetto LM, D'Andrea MR, Rossi E, Monfardini S. Oxaliplatin-related neurotoxicity: how and why? Crit Rev Oncol Hematol. 2006 Aug;59(2):159-68. Epub 2006 Jun 27. PMID 16806962.
3. ^ ^{a b} Orange Book. accessdata.fda.gov. URL: http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021759&Product_No=001&table1=OB_Rx. Accessed on: July 22, 2007.

Additional sources

• Graham J, Mushin M, Kirkpatrick P (2004). "Oxaliplatin." (PDF). Nat Rev Drug Discov 3 (1): 11-2. PMID 14756144.