Carboplatin dose calculations for patients with lung cancer: significant dose differences found depending on dosing equation choice

Abstract

Abstract Background Carboplatin is the backbone cytotoxic agent for many chemotherapy regimens for lung cancer. Dosing of carboplatin is complicated due to its relationship to renal function and narrow therapeutic index. Overestimation of renal function may lead to supratherapeutic dosing and toxicity, while underestimation may lead to underdosing and therapeutic failure. Although the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have higher accuracy in estimating glomerular filtration rate (eGFR), the Cockcroft Gault (CG) formula has been historically used for carboplatin dosing internationally. Methods We compared these formulae to identify patient profiles that were associated with significant carboplatin dose variation by retrospectively analysing the carboplatin dosing of 96 patients with lung cancer. Carboplatin doses were calculated using eGFR generated by MDRD, CKD-EPI 2009 and CKD-EPI 2021 equations. These three hypothetical doses were compared to actual CG-based doses prescribed. Results MDRD and CKD-EPI equations resulted in comparable carboplatin doses; however, CG doses diverged markedly with up to 17% of the patients receiving a carboplatin dose that was at least 20% higher than a non-CG formula would have predicted, and 20% received a dose that was at least 20% lower than a non-CG formula would have predicted. Our data suggest CG use overestimates kidney function in patients with a higher bodyweight and body surface area (BSA) while underestimating it in patients with a lower bodyweight and BSA. Importantly, we demonstrate potential real-world benefit as CKD-EPI predicted lower doses for patients whose (CG-derived) carboplatin dose was later reduced following clinical assessment prior to infusion. Conclusions We have therefore confirmed significant differences in carboplatin dosing depending on the equation used in our modern patient population and suggest that use of CKD-EPI provides the most clinically appropriate carboplatin dosing and should be implemented as the new standard of care internationally.

Keywords

• Lung cancer
• Carboplatin
• Drug toxicity
• Kidney function
• eGFR
• Cockcroft-Gault