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 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®.

Mechanism of action and efficacy

In vivo studies showed oxaliplatin has anti-tumour 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)
  • Fatigue
  • Nausea, vomiting, and/or diarrhoea
  • Neutropaenia
  • Hearing loss

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

    History

    Oxaliplatin was discovered in 1976 at Nagoya 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). 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 tumour-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.

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