Introduction
Carboplatin is an organoplatinum antineoplastic alkylating agent used in the treatment of advanced ovarian carcinoma. Early clinical studies of carboplatin were performed in 1982. Carboplatin was developed as an analog of cisplatin with reduced nephrotoxicity and vomiting.
Uses
Carboplatin is a alkylating agent used to treat advanced ovarian cancer.
Carboplatin is indicated in combination with an established combination of chemotherapeutic agents for the initial treatment of advanced ovarian carcinoma. Carboplatin is also indicated for the palliative treatment of ovarian carcinoma, recurrent after prior chemotherapy.
Associated Conditions
Pharmacodynamics
Carboplatin is an organoplatinum antineoplastic alkylating agent used in the treatment of advanced ovarian carcinoma. Carboplatin has a long duration of action as it is given every 4 weeks, and a narrow therapeutic index. Patients should be counselled regarding bone marrow suppression and anemia.
Mechanism of Action
Carboplatin predominantly acts by attaching alkyl groups to the nucleotides, leading to the formation of monoadducts, and DNA fragmenting when repair enzymes attempt to correct the error. 2% of carboplatin's activity comes from DNA cross-linking from a base on one strand to a base on another, preventing DNA strands from separating for synthesis or transcription. Finally, carboplatin can induce a number of different mutations.
Absorption
The Cmax and AUC of carboplatin increase proportionally with increasing doses. A 75 mg/m2 A 450 mg/m2
Volume of Distribution
The apparent volume of distribution after a 30 minute intravenous infusion of 300-500 mg/m2 was 16 L.
Protein Binding
Carboplatin is not bound to plasma protein. However, the free platinum is 40% irreversibly bound to plasma proteins.
Route of Elimination
Carboplatin is 65% eliminated in the urine within 12 hours, and 71% eliminated within 24 hours. An additional 3-5% is eliminated in urine from 24 hours to 96 hours. Biliary elimination has not been determined. Carboplatin is predominantly eliminated as the unchanged parent compound.
Half Life
The distribution half life of carboplatin is 1.1-2 hours, and the elimination half life was2.6-5.9 hours.
Clearance
The total body clearance after a 30 minute intravenous infusion of 300-500 mg/m2 was 4.4 L/h.
Toxicity
Patients experiencing an overdose of carboplatin may present with pronounced neutropenia and hepatotoxicity. Treat patients with symptomatic and supportive measures, which may include delaying their next treatment.
Food Interactions
- Avoid echinacea. Co-administration may decrease effectiveness of immunosuppressants.
Dosage
After dilution, Carboplatin should be used by the intravenous route only. The recommended dosage of Carboplatin in previously untreated adult patients with normal kidney function is 400 mg/m2 as a single I.V. dose administered by a 15 to 60 minute infusion. Therapy should not be repeated until four weeks after the previous Carboplatin course and/or until the neutrophil count is at least 2000 cells/mm3 and the platelet count is at least 100,000 cells/mm3 . Reduction of the initial dosage by 20-25% (i.e, 300-320 mg/m2) is recommended for those patients who present with risk factors such as prior myelosuppressive treatment and low performance status (ECOG-Zubrod 2-4 or Karnofsky below 80). For patients age 65 and over, dosage adjustment, initially or subsequently, may be necessary, dependent on the physical condition of
the patient.
Determination of the hematologic nadir by weekly blood count during the initial courses of treatment with Carboplatin is recommended for dosage adjustment for subsequent courses of therapy.
