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Carboplatin is dosed by kidney function rather than body size, using a formula from 1989 that aims at a set drug exposure. The formula is only as good as the kidney measurement fed into it: in a study of 2,471 people with cancer, the usual blood-test estimates missed the intended dose by more than a fifth in about one person in five to one in four.
The formula. Carboplatin leaves the body almost entirely through the kidneys. Calvert and colleagues found that its clearance rose in a straight line with glomerular filtration rate, and after testing the first version prospectively in 31 patients they recommended dose in milligrams equals the target exposure multiplied by the filtration rate plus 25. Exposure is expressed as an area under the curve in milligrams per millilitre per minute; they recommended targets of 5 for previously treated and 7 for untreated patients on carboplatin alone, and noted that the target would have to be set again for combinations. Because the formula aims at exposure rather than toxicity, it carries over to combination and high-dose treatment.
Where the error enters. Filtration rate can be measured directly, by clearance of an injected tracer such as chromium-51 EDTA, or estimated from a blood creatinine level with an equation. A Cambridge study of 2,471 patients with cancer compared seven published equations with measured clearance. The best published equation, CKD-EPI adjusted for body surface area, still gave a carboplatin dose more than 20 per cent away from the dose measured clearance would give in 18.6 per cent of patients, and the Cockcroft-Gault equation did so in 25.5 per cent; a new equation built on the same data brought that to 14.2 per cent. The study included white patients only. Creatinine comes from muscle, so it misleads most in people with little muscle: in 545 patients with cancer measured on CT, sarcopenia and high body fat each roughly doubled the odds that creatinine and cystatin C estimates disagreed by more than 30 per cent, and 48 per cent of the whole group had a disagreement that large.
The next step. Cystatin C is less affected by muscle mass, though the 2024 study notes it may underestimate kidney function in obesity. A multicentre study of 357 patients built a carboplatin clearance equation from creatinine, cystatin C, weight, age and sex, with a bias of 1 per cent and an imprecision of 15 per cent, similar in underweight, normal-weight and obese patients. OnCo found no trial showing that more precise filtration measurement changes survival or toxicity; the evidence is about hitting the intended exposure.
Carboplatin clearance is approximately glomerular filtration rate plus a small non-renal component, so dose (mg) = target AUC (mg/mL·min) × (GFR in mL/min + 25).
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