Oxaliplatin, marketed as Eloxatin by Sanofi, is a platinum-based antineoplastic agent used

in cancer chemotherapy.[2]
It is on the World Health Organization's List of Essential Medicines, a list of the most
important medications needed in a basic health system.[3]

Contents

1 History
2 Structure and mechanism

3 Clinical use
o

3.1 Advanced colorectal cancer

3.2 Adjuvant treatment of colorectal cancer

4 Adverse effects

5 Patent information

6 References

7 External links

8 Additional sources

History
Oxaliplatin was discovered in 1976 at Nagoya City University by Professor Yoshinori Kidani,
who was granted U.S. Patent 4,169,846 in 1979. Oxaliplatin was subsequently in-licensed by
Debiopharm and developed as an advanced colorectal cancer treatment. Debio licensed the
drug to Sanofi-Aventis in 1994. It gained European approval in 1996 (initially in France) and
approval by the U.S. Food and Drug Administration in 2002. Generic oxaliplatin was first
approved in the United States in August 2009.[4] In 2010, Sanofi regained exclusivity
protection for the drug until August 2012.[5]

Structure and mechanism

The compound features a square planar platinum(II) center. In contrast to cisplatin and
carboplatin, oxaliplatin features the bidentate ligand 1,2-diaminocyclohexane in place of the
two monodentate ammine ligands. It also features a bidentate oxalate group.[6]
According to in vivo studies, oxaliplatin fights carcinoma of the colon through non-targeted
cytotoxic effects. Like other platinum compounds, its cytotoxicity is thought to result from
inhibition of DNA synthesis in cells. In particular, oxaliplatin forms both inter- and intrastrand cross links in DNA,[7] which prevent DNA replication and transcription, causing cell
death.

Clinical use

Oxaliplatin is used for treatment of colorectal cancer, typically along with folinic acid and 5fluorouracil in a combination known as FOLFOX. Oxaliplatin has been compared with other
platinum compounds used for advanced cancers, such as cisplatin and carboplatin.

Advanced colorectal cancer

In clinical studies, oxaliplatin by itself has modest activity against advanced colorectal
cancer.[8] When compared with just 5-fluorouracil and folinic acid administered according to
the de Gramont regimen, a FOLFOX4 regime produced no significant increase in overall
survival, but did produce an improvement in progression-free survival, the primary end-point
of the phase III randomized trial.[9]

Adjuvant treatment of colorectal cancer

After and/or before[10] the curative resection of colorectal cancer, chemotherapy based on 5fluorouracil and folinic acid reduces the risk of relapse. The benefit is clinically relevant
when cancer has spread to locoregional lymph nodes or penetrated through the wall of the
rectum or colon (stage III, Dukes C). The addition of oxaliplatin improves relapse-free
survival, but data on overall survival have not yet been published in extenso.
When cancer has not spread to the locoregional lymph nodes, nor penetrated through the wall
of the rectum or colon (stage II, Dukes B) the benefit of chemotherapy is marginal and the
decision on whether to give adjuvant chemotherapy should be carefully evaluated by
discussing with the patient the realistic benefits and the possible toxic side effects of
treatment. This is even more relevant when the oncologist proposes treatment with
oxaliplatin.

Adverse effects
Side-effects of oxaliplatin treatment can potentially include:

Neurotoxicity leading to chemotherapy-induced peripheral neuropathy, a progressive,

enduring and often irreversible tingling numbness, intense pain and hypersensitivity
to cold, beginning in the hands and feet and sometimes involving the arms and legs,
often with deficits in proprioception.[11]
Fatigue

Nausea, vomiting, or diarrhea

Neutropenia (low number of a type of white blood cells)

Ototoxicity (hearing loss)

Extravasation if oxaliplatin leaks from the infusion vein it may cause severe damage
to the connective tissues.

Hypokalemia (low blood potassium), which is more common in women than men[12]

Persistent hiccups[13]

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

This is more common in women.[12]

Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin.[11]

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).[14] Exclusivity code I-441, which expired 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, expired on Aug 09, 2007.[14]