Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer.[ This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma.][ It is administered by intravenous sometimes via a port.]
Side effects generally occur.[ Common side effects include cytopenia, nausea, and electrolyte problems.][ Other serious side effects include allergic reactions and mutagenesis. It may be carcinogenic, but further research is needed to confirm this.]
Carboplatin was developed as a less toxic analogue of cisplatin.
Medical uses
Carboplatin is used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It may be used for some types of testicular cancer but cisplatin is generally more effective.[ It has also been used to treat triple-negative breast cancer. Carboplatin has also been used for adjuvant therapy of stage 1 seminoma. Research has indicated that it is not less effective than adjuvant radiotherapy for this treatment, while having fewer side effects.]
Side effects
Relative to cisplatin, the greatest benefit of carboplatin is its reduced side effects, particularly the elimination of nephrotoxicity effects. Nausea and vomiting are less severe and more easily controlled.
The main drawback of carboplatin is its myelosuppressive effect. This causes the blood cell and platelet output of bone marrow in the body to decrease quite dramatically, sometimes as low as 10% of its usual production levels. The nadir of this myelosuppression usually occurs 21–28 days after the first treatment, after which the blood cell and platelet levels in the blood begin to stabilize, often coming close to its pre-carboplatin levels. This decrease in white blood cells (neutropenia) can cause complications, and is sometimes treated with drugs like filgrastim. The most notable complication of neutropenia is increased probability of infection by opportunistic organisms, which necessitates hospital readmission and treatment with .
Mechanism of action
Carboplatin differs from cisplatin in that it has a bidentate dicarboxylate (the ligand is cyclobutane dicarboxylate, CBDCA) in place of the two chloride . Both drugs are in the platinum-based antineoplastic family of medications. CBDCA and chloride are the labile ligands in these respective drugs. Carboplatin exhibits slower aquation (replacement of CBDCA by water) and thus slower DNA binding kinetics, although it forms the same reaction products in vitro at equivalent doses with cisplatin. Unlike cisplatin, carboplatin may be susceptible to alternative mechanisms. Some results show that cisplatin and carboplatin cause different morphological changes in MCF-7 cell lines while exerting their cytotoxic behaviour.
Like cisplatin, carboplatin binds to and cross-links DNA, interfering with the replication and suppressing growth of the cancer cell.
Dose calculation using Calvert's equation
Prior to 1989, most carboplatin dosing used body surface area dosing as with other chemotherapy. However, toxicity from treatment was variable, and therefore Professor Hillary Calvert (University of Newcastle) developed a formula to dose carboplatin based on renal function.
Calvert's formula considers the creatinine clearance and the desired area under curve.
Calvert formula:
The typical area under the curve (AUC) for carboplatin ranges from 3-7 (mg/ml)*min.
The Calvert formula was developed in 18 patients with GFR measurements up to 133ml/min.
Synthesis
Cisplatin reacts with silver nitrate and then cyclobutane-1,1-dicarboxylic acid to form carboplatin.
History
Carboplatin, a cisplatin analogue, was developed by Bristol Myers Squibb and the Institute of Cancer Research in order to reduce the toxicity of cisplatin.
Further reading
