Oxaliplatin 63121-00-6
61825-94-3
Oxaliplatin is a coordination complex that is used in cancer chemotherapy. These platinum-based drugs are usually classified as alkylating agents, although they are actually alkylating groups (they function by a similar mechanism).
Preparation and structure
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. Eloxatin gained European approval in 1996 (firstly in France) and approval by the U. S. Food and Drug Administration (FDA) in 2002. 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.
Mechanism of action
The cytotoxicity of platinum compounds is thought to result from inhibition of DNA synthesis in cancer cells. In vivo studies showed that Oxaliplatin has anti-tumor activity against colon carcinoma through its (non-targeted) cytotoxic effects.
Clinical use
Oxaliplatin is typically administered with fluorouracil and leucovorin in a combination known as FOLFOX for the treatment of colorectal cancer. Oxaliplatin is marketed by Sanofi-Aventis under the trademark Eloxatin or by Medac GmbH under the trademark Oxaliplatin Medac. There are generic equivalents on the market now Oxaliplatin has been compared with other platinum compounds (Cisplatin, Carboplatin) in advanced cancers (gastric, ovarian).
Advanced colorectal cancer
In clinical studies, Oxaliplatin by itself has modest activity against advanced colorectal cancer. It has been extensively studied in combination with Fluorouracil and Folinic Acid (a combination known as FOLFOX). When compared with Fluorouracil and Folinic Acid administered according to the "De Gramont regimen" there was no significant increase in overall survival with the FOLFOX regimen (specifically, FOLFOX4), but progression-free survival, the primary end-point of the phase III randomized trial, was improved with FOLFOX.
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:
- 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 diarrhea
- Neutropenia
- Ototoxicity (hearing loss)
- Extravasation if Oxaliplatin leaks from the infusion vein it may cause severe damage to the connective tissues.
In addition, some patients may experience an allergic reaction to platinum-containing drugs. Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin. 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.
| Systematic (IUPAC) name: | [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O)platinum(II) |
|---|---|
| Oxaliplatin CAS number: | 63121-00-6 61825-94-3 |
| ATC code: | L01XA03 |
| PubChem: | 77994 |
| DrugBank: | APRD00186 |
| Formula: | C8H14N2O4 |
| Molecular mass: | 397.2858 g/mol |
| Oxaliplatin Assay/Purity: | Typically NLT 98% |
