Carboplatin is one of the platinum-based anti-cancer drugs and its parent compound is cisplatin. Carboplatin has gained significant popularity since its introduction in the 1980s because it causes less side effects than cisplatin.
Mechanism of action
Carboplatin undergoes activation inside cells and forms reactive platinum complexes that cause the intra- and inter-strand cross-linkage of DNA molecules within the cell. This modifies the DNA structure and inhibits DNA synthesis. This may affect a cell in all the phases of its cycle.
After a 1 hour infusion of carboplatin, the blood levels of total platinum and free platinum reduce in a biphasic manner. For the free platinum, the first phase of the half life (when the drug achieves half its plasma concentration) is around 90 minutes. In the later phase, the half life is around 6 hours. All free platinum is in the form of carboplatin for the first four hours.
Once administered, the drug binds to plasma proteins. Protein binding is less than with cisplatin. Initially, protein binding is low, with around 29% of the carboplatin bound in the first 4 hours. However, within 24 hours, 85-89% of the platinum in the drug is bound irreversibly to the plasma proteins and is gradually eliminated with a minimum half life of five days.
Carboplatin is excreted via the kidneys. Most of the excretion occurs within the first 6 hours after the drug is administered and around 50% to 60% is excreted within 24 hours. Of all the medication administered, 32% is excreted unchanged in urine.
Dose and administration
Carboplatin is given as an intravenous infusion over half an hour to 1 hour, usually as a day care procedure. The carboplatin is usually administered to a vein in the arm using a cannula or if the site of administration is a large vein in the neck, a central venous catheter is used. Patients may have an implantable venous access port embedded under their skin, which is used in cases where intravenous treatment is used in the long-term.
The recommended dosage for previously untreated adults who have a normal kidney function is 400 mg/m² over 15 to 60 minutes. The dose is determined as per the person’s body surface area rather than weight alone. Each infusion is not repeated for 4 weeks. The dose may need to be reduced by 20% to 25% in patients with low blood counts or poor kidney function.
Among kidney damaged individuals, the dose is determined as per the creatinine clearance. The following acts as an approximate guide:
- Creatinine Clearance > 40 mL/min – Dose of Carboplatin 400 mg/m²
- Creatinine Clearance 20-39 mL/min – Dose of Carboplatin 250 mg/m²
- Creatinine Clearance 0-19 mL/min – Dose of Carboplatin 150 mg/m²
When is carboplatin used?
Carboplatin is mainly used to treat ovarian cancer and lung cancer. Other forms of cancer where carboplatin may be indicated include cancers of the head and neck, breast, cervix, esophagus, breast, bladder and central nervous system. It may also be used to prepare a patient for a stem cell or bone marrow transplant.
Carboplatin should not be used to treat patients with the following conditions:
- Severe kidney disease
- Allergy to carboplatin
- Severe bone marrow depression
- Severe bleeding
- Pregnant and breastfeeding women
Side effects of carboplatin
Some examples of the side effects that occur with carboplatin treatment include:
- Nausea and vomiting
- Mouth ulcers and loss of appetite
- Bone marrow suppression leading to anemia, low platelet counts leading to bleeding tendencies and low white blood cell counts leading to increased susceptibility to infection.
- Kidney and liver function may be affected.
- Hearing loss may be seen, especially in children receiving carboplatin.
- There may be short-term vision loss. Improvement and/or total recovery of vision usually occurs within weeks after the drug is discontinued.
- Hearing loss, especially in children receiving the therapy.
- Hair loss (this is usually regained after completion of therapy).
- Rarely, allergic reactions occur such as skin rashes, itching, fever and shivering. If any of these symptoms occur, medical attention should be sought immediately.