Dosage of carboplatin

Initially, a dosage of carboplatin based on body-surface area resulted in a variable degree of thrombocytopenia with a number of patients requiring platelet transfusion. Pharmacokinetically-based dosing is now the adopted standard.

With simple pharmacokinetics, about 65% of an administered dose of carboplatin is excreted in the urine within 24 hours and renal clear ance is virtually the same as the glomerular filtration rate (GFR). The remaining drug remains covalently bound to tissues for long periods (months to years) and is biologically inert.

Antiproliferative toxicities of carboplatin are related to drug concentration and time, which is given by the area under the plasma concentration time curve (AUC). The simple pharmacokinetics of carboplatin allow a dosing formula to be derived from which the dose required to achieve a specific AUC can be calculated for an individual patient. The most widely used formula is:

Where:

Dose is the total dose in mg to be given to the patient.

H is the desired AUC in mg/ml.mm. Typical AUCs are between 4 and 7, depending on frequency of administration, previous treatment, and the drugs being used in combination.

GFR is glomerular filtration rate of patient (ml/min), unadjusted for surface area (should ideally be measured by an isotope method such as 51CrEDTA clearance, but a carefully performed 24-hour urinary creatinine clearance is also acceptable).

AUC-based dosing results in a predictable toxicity and the administration of a larger average dose. AUC has largely superseded surface area-based dosing. When high-dose carboplatin is used with stem-cell rescue regimens there appears to be a relationship between AUC and non-haematological toxicities.

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