Calvert Formula Modification for Optimized Carboplatin Dosing in Breast Cancer with Preserved Renal Function

Background/Objectives: Although the Calvert formula has been widely used to guide carboplatin dosing, it may yield inaccurate dose predictions in certain patient populations. We aimed to evaluate the adequacy of the conventional Calvert formula and to propose structural modifications to enhance dosing accuracy in breast cancer patients with preserved renal function (CrCL ≥ 55 mL/min). Methods: A systematic review and meta-analysis were conducted to integrate published pharmacokinetic models in patients with breast cancer. Two retrospective datasets (n = 154) were combined into a single analysis dataset and used to calculate carboplatin doses based on the conventional formulas using creatinine clearance (CrCL) or estimated glomerular filtration rate (eGFR), as well as a modified formula incorporating an additional constant (α). Performance was assessed by the proportion of subjects achieving target area under the curve (AUC) attainment (4-6 mg·min/mL), underexposure (<4 mg·min/mL), and overexposure (≥7 mg·min/mL). All AUC metrics were derived from model-based predictions rather than measured carboplatin concentrations, and no clinical toxicities or efficacy outcomes were used for validation. Results: Meta-analysis yielded fixed-effect parameter estimates (CL: 131.8 mL/min, V₁: 15.39 L, K₁₂: 0.002 min^-1, and K₂₁: 0.003 min^-1) with a random effect model. The conventional CrCL-based formula yielded 66.0% target attainment, 22.1% underexposure, and 4.5% overexposure. Switching to eGFR improved attainment to 88.3%, reduced underexposure to 5.8%, and lowered overexposure to 0.65%. A modified formula with α = 1 further decreased underexposure (4.5%) while target attainment and overexposure remained unchanged. Conclusions: Replacing CrCL with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-derived eGFR in the Calvert formula markedly improved dosing accuracy, while modest structural modification offered additional benefit. The incremental benefit of α = 1 should be considered hypothesis-generating and requires prospective validation with measured carboplatin concentrations and clinical outcomes before applying it in practice. These findings support adopting eGFR-based dosing in breast cancer and suggest the need for future clinical validation.