Oxaliplatin (CAS: 61825-94-3,63121-00-6)

Oxaliplatin (pronounced ox-ally-plat-in), marketed as Eloxatin by

Sanofi, is a platinum-based antineoplastic agent used in cancer

chemotherapy.

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 inFrance) and approval by the U.S.

Food and Drug Administration in 2002. Generic oxaliplatin was first approved in

theUnited Statesin August 2009. In 2010, Sanofi regained exclusivity protection

for the drug until August 2012.

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.

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 cancer cells. In particular, oxaliplatin forms both inter- and

intra-strand cross links in DNA, 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

fluorouracil 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.

When compared with just 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.

Adjuvant treatment of colorectal cancer

After the curative resection of colorectal cancer, chemotherapy based on fluorouracil and folinic

acid reduces the risk of relapse. The benefit is clinically relevant when cancer has spread to

locoregional lymph nodes (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 (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.[8]

•     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

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

This is more common in women.

Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin.