Effect of Dosing Equation for Carboplatin on Related Adverse Events

The cancer drug carboplatin is known to cause adverse events (AEs). Excess dosing of carboplatin may occur because the Calvert equation for dosing usually uses Cockcroft-Gault creatinine clearance (CG), and this may lead to an overestimation of measured glomerular filtration rate (GFR).

A prospective study being presented at the National Kidney Foundation Spring Clinical Meetings 2025 compared carboplatin dosing using Chronic Kidney Disease Epidemiology Collaboration creatinine and cystatin C (eGFR-CR-CYS) and evaluated the association between excess dosing and AEs.

Study participants comprised 292 adults with cancer (lung, n=106 [36%]; gynecologic, n=94 [32%]; intestinal, n=35 [12%]; breast, n=31 [11%]) who began receiving carboplatin between 2023 and 2025 and whose creatinine and cystatin C were measured before the first dose. Mean (±SD) participant age was 66±11.7 years, and 193 participants (66%) were women.

The researchers compared the dose administered based on CG with the dose calculated using eGFR-CR-CYS. They defined an excess dose of carboplatin as a dose more than 15% higher than the dose calculated using eGFR-CR-CYS and underdosed as a dose less than 15% lower than the dose calculated using eGFR-CR-CYS. They used a Fine-Gray model to determine the association between excess dose and cytopenia, acute kidney injury (AKI), and hospitalizations and a Cox model to determine mortality.

Calculating dosing with eGFR-CR-CYS resulted in clinically significant dose adjustments for 76 study participants (26%). Of those, 35 (12%) received an excess dose and 41 (14%) were underdosed. Receiving an excess dose was associated with a higher risk of anemia, thrombocytopenia, acute kidney injury of grade 3 or higher, and death within 90 days.

The results highlight the discrepancies between dosing calculations made using CG and eGFR-CR-CYS. Using the latter might help identify patients for whom a dose reduction could result in fewer AEs.

Source: Khor SY, Lye J, Mejia S, et al. Re-defining carboplatin dosage using eGFR-creatinine-cystatin C compared to Cockcroft Gault and impact on platinum-associated adverse events. Abstract #LB-02. Presented at the National Kidney Foundation Spring Clinical Meetings 2025; April 10-13, 2025; Boston, MA.