Oxaliplatin
[CAS# 61825-94-3]

Identification

• Classification: API >> Antineoplastic agents >> Other antineoplastic agents
• Name: Oxaliplatin
• Synonyms: trans-L-Diaminocyclohexane oxalatoplatinum
• Molecular Formula: C₈H₁₂N₂O₄Pt
• Molecular Weight: 395.27
• CAS Registry Number: 61825-94-3
• EC Number: 621-248-1
• SMILES: C1CC[C@H]([C@@H](C1)N)N.C(=O)(C(=O)[O-])[O-].[Pt+2]

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H302-H315-H317-H319-H334-H335-H340-H350-H351-H360-H360
• Safety Statements: P203-P233-P260-P261-P264-P264+P265-P270-P271-P272-P280-P284-P301+P317-P302+P352-P304+P340-P305+P351+P338-P318-P319-P321-P330-P332+P317-P333+P317-P337+P317-P342+P316-P362+P364-P403-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin sensitization	Skin Sens.	1	H317
Eye irritation	Eye Irrit.	2	H319
Carcinogenicity	Carc.	2	H351
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Respiratory sensitization	Resp. Sens.	1	H334
Reproductive toxicity	Repr.	1B	H360
Germ cell mutagenicity	Muta.	1B	H340
Germ cell mutagenicity	Muta.	2	H341
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Acute toxicity	Acute Tox.	3	H301
Carcinogenicity	Carc.	1B	H350
Reproductive toxicity	Lact.	-	H362
Acute toxicity	Acute Tox.	2	H300
Specific target organ toxicity - single exposure	STOT SE	3	H336
Acute toxicity	Acute Tox.	4	H302
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H331
Reproductive toxicity	Repr.	1A	H360

Discovery and Applications

Oxaliplatin is a platinum-based chemotherapy drug used primarily in the treatment of colorectal cancer. It is a third-generation platinum compound, which functions similarly to other platinum drugs such as cisplatin and carboplatin but with a distinct structure that contributes to its unique properties. Oxaliplatin is an organoplatinum complex, consisting of a platinum ion coordinated to two ammonia molecules and a bulky oxalate ligand. The drug was developed to overcome the limitations of earlier platinum-based agents, particularly in terms of their side effect profiles and resistance mechanisms.

Oxaliplatin was discovered in the late 1980s by a group of researchers led by Alain B. M. in the field of medicinal chemistry. The initial goal was to develop platinum compounds that could circumvent the common side effects associated with cisplatin, such as nephrotoxicity, ototoxicity, and peripheral neuropathy. Cisplatin, despite being one of the most effective anticancer drugs, often caused severe kidney damage, leading researchers to explore new platinum complexes with reduced toxicity. Oxaliplatin emerged as a promising candidate due to its ability to bind to DNA in a similar manner to cisplatin but with a reduced tendency to cause kidney damage.

The primary mechanism of action of oxaliplatin involves the formation of platinum-DNA adducts, which disrupt the normal structure of DNA. These adducts inhibit DNA replication and transcription, leading to apoptosis or programmed cell death in rapidly dividing cancer cells. The presence of the oxalate ligand, which is a bidentate ligand, distinguishes oxaliplatin from other platinum drugs, contributing to its ability to form more stable DNA adducts and to overcome certain resistance mechanisms that affect cisplatin.

Oxaliplatin is commonly used in combination with other chemotherapy drugs as part of a treatment regimen for colorectal cancer, particularly in the FOLFOX regimen, which combines oxaliplatin with 5-fluorouracil (5-FU) and leucovorin. This combination has proven to be highly effective in the treatment of advanced colorectal cancer and is often used as a first-line therapy. In addition to colorectal cancer, oxaliplatin is also being investigated for its potential efficacy in treating other cancers, including pancreatic cancer, gastric cancer, and ovarian cancer.

Despite its improved side effect profile compared to cisplatin, oxaliplatin is not without adverse effects. One of the most significant side effects is peripheral neuropathy, which can range from mild tingling or numbness to more severe pain or loss of motor function. This side effect is dose-dependent and can be exacerbated by repeated cycles of treatment. While the neuropathy is often reversible after discontinuation of the drug, it can significantly impact a patient's quality of life during treatment. Other common side effects include nausea, vomiting, diarrhea, and hematologic toxicity, such as neutropenia, which can increase the risk of infection.

Oxaliplatin is administered intravenously, and its dosage is typically based on body surface area. The drug is usually given as part of a chemotherapy regimen that may involve multiple cycles, depending on the type and stage of cancer being treated. The use of oxaliplatin in combination with other agents, such as 5-FU, helps to enhance its efficacy and improve treatment outcomes.

The development of resistance to oxaliplatin is a significant challenge in clinical oncology. Resistance mechanisms may involve alterations in drug uptake, efflux, or DNA repair processes that allow cancer cells to survive despite the presence of the drug. Research into overcoming oxaliplatin resistance is ongoing, with strategies being developed to modify the drug's structure, enhance its delivery, or combine it with other agents that can overcome resistance.

In addition to its role in chemotherapy, oxaliplatin has been studied for its potential use in combination with targeted therapies and immunotherapies. These combinations aim to improve the overall efficacy of cancer treatment by targeting multiple pathways involved in cancer cell survival and proliferation. The continued exploration of oxaliplatin in combination therapies offers hope for more effective and personalized treatments for cancer patients.

In conclusion, oxaliplatin is a crucial drug in the treatment of colorectal cancer and other malignancies. Its unique properties, including its ability to circumvent certain resistance mechanisms and reduce nephrotoxicity, make it an important part of modern chemotherapy regimens. While side effects, particularly peripheral neuropathy, remain a challenge, the ongoing research into combination therapies and mechanisms of resistance may further improve the efficacy and safety of oxaliplatin in the future.

References

1998. Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: A phase II multicentric study. Annals of Oncology, 9(1).
DOI: 10.1023/a:1008200825886

2005. Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I-II study. Annals of Oncology, 16(5).
DOI: 10.1093/annonc/mdi154

2025. Oxaliplatin-loaded amphiphilic hyaluronic acid nanohydrogel formed via interfacial reactions enhances the therapeutic effect of targeted tumor. International Journal of Biological Macromolecules, 287.
DOI: 10.1016/j.ijbiomac.2024.138118