Carboplatin
[CAS# 41575-94-4]

Identification

• Classification: API >> Antineoplastic agents >> Other antineoplastic agents
• Name: Carboplatin
• Synonyms: 1,1-Cyclobutanedicarboxylatodiammineplatinum (II); Paraplatin; cis-Diamine(1,1-cyclobutanedicarboxylato)platinum(II)
• Molecular Formula: C₆H₁₂N₂O₄Pt
• Molecular Weight: 371.25
• CAS Registry Number: 41575-94-4
• EC Number: 255-446-0
• SMILES: C1CC(C1)(C(=O)O)C(=O)O.[NH2-].[NH2-].[Pt+2]

Properties

• Solubility: DMSO $lessThan$ 1mg/ml, Water $lessThan$1 mg/ml (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H302-H302-H302-H312-H317-H319-H332-H334-H340-H350-H360-H360D-H362
• Safety Statements: P203-P233-P260-P261-P263-P264-P264+P265-P270-P271-P272-P280-P284-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P318-P321-P330-P333+P317-P337+P317-P342+P316-P362+P364-P403-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin sensitization	Skin Sens.	1	H317
Respiratory sensitization	Resp. Sens.	1	H334
Germ cell mutagenicity	Muta.	1B	H340
Acute toxicity	Acute Tox.	4	H312
Reproductive toxicity	Repr.	1B	H360
Acute toxicity	Acute Tox.	4	H332
Eye irritation	Eye Irrit.	2	H319
Reproductive toxicity	Lact.	-	H362
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Carcinogenicity	Carc.	2	H351
Specific target organ toxicity - single exposure	STOT SE	3	H335
Reproductive toxicity	Repr.	2	H361
Germ cell mutagenicity	Muta.	2	H341
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Carcinogenicity	Carc.	1B	H350
Specific target organ toxicity - single exposure	STOT SE	1	H370
Carcinogenicity	Carc.	1A	H350

• Transport Information: UN 2811

Discovery and Applications

Carboplatin is a chemotherapy drug used in the treatment of various types of cancer, including ovarian cancer, lung cancer, and other solid tumors. It is a platinum-based compound, similar to cisplatin, but with modifications that make it more effective and less toxic in certain situations.

Carboplatin was first synthesized in the late 1980s as part of efforts to develop less toxic alternatives to cisplatin, which, despite being effective, caused significant side effects such as nephrotoxicity (damage to the kidneys), neurotoxicity (nerve damage), and ototoxicity (hearing loss). Carboplatin contains a platinum center coordinated with two ammine ligands and a cyclobutane diolato group, which differentiates it from cisplatin, which has chloride ligands. This structural modification reduces the overall reactivity of carboplatin, thereby lowering its toxicity while maintaining its anticancer activity.

The mechanism of action of carboplatin involves its interaction with the DNA in cancer cells. Like other platinum-based chemotherapy drugs, carboplatin forms covalent bonds with the DNA, causing cross-links between the DNA strands. These cross-links prevent the cancer cell from replicating its DNA, thereby halting cell division and leading to cell death. The drug is particularly effective against rapidly dividing cells, which is why it is useful in treating cancers where cells proliferate quickly.

Carboplatin is administered intravenously and is typically used in combination with other chemotherapy agents to increase its effectiveness. The drug is often preferred over cisplatin in patients who are at higher risk for kidney damage, as its reduced nephrotoxicity makes it a safer option in these cases. It is also used in patients who have previously been treated with cisplatin and have developed resistance to it, as carboplatin may work in cases where cisplatin is no longer effective.

While carboplatin is generally better tolerated than cisplatin, it still has side effects. The most common adverse effects include myelosuppression (a decrease in bone marrow activity, leading to low blood cell counts), nausea and vomiting, and hair loss. However, carboplatin’s side effects are typically less severe than those of cisplatin, which makes it a preferred option for some patients.

The discovery and development of carboplatin marked a significant step forward in cancer chemotherapy, providing a more tolerable option for patients requiring platinum-based treatment. Its clinical success has led to the approval of several similar platinum compounds, including oxaliplatin, which also aim to provide effective cancer treatment with reduced side effects.

In conclusion, carboplatin is an important chemotherapy drug that provides an effective and less toxic alternative to cisplatin for the treatment of various cancers. Its ability to form DNA cross-links and inhibit cell division makes it a valuable tool in cancer therapy, and its reduced toxicity profile has improved the quality of life for many patients undergoing cancer treatment.

References

2003. Carboplatin dosing accounting for the renal and hematologic status of patients. Clinical Journal of Oncology Nursing, 7(1).
DOI: 10.1188/03.cjon.104-108

2005. Carboplatin hypersensitivity induced by low-dose paclitaxel/carboplatin in multiple platinum-treated patients with recurrent ovarian cancer. International Journal of Gynecological Cancer, 15(2).
DOI: 10.1111/j.1525-1438.2005.15207.x

2005. Combination therapy with gemcitabine and carboplatin in recurrent ovarian cancer. International Journal of Gynecological Cancer, 15(Suppl 1).
DOI: 10.1111/j.1525-1438.2005.15355.x