Abstract C063: Discrepancies Between Calculated and Actual Creatinine Clearance: A Phase 1 Trial Unit Experience

Abstract Background: Cockcroft-Gault formula (CGF) is the most frequently used formula for calculating creatinine clearance (CrCl) as part of evaluating patients’ eligibility for clinical trial enrollment. However, CGF was originally developed in a different patient population with the main purpose of predicting CrCl measured through 24-hour urine collection. Despite further modifications adjusting for the impact of sex, its ability to accurately predict CrCl in patients with advanced cancers remains controversial. Herein, we looked into the correlations between CrCl calculated using CGF and that estimated using 24-hour urine collection in a cancer patient population that was being evaluated for enrollment in phase 1 clinical trials. Methods: We included patients who were seen in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center (Houston, TX) and had 24-hour urine collection for estimation of CrCl. We defined CrClactual as that estimated through the 24-hour urine collection and CrClcalculated as that estimated using CGF [(140–age)×(weight in kg)×(0.85 if female)/(72×serum creatinine in mg/dL)]. Underestimation of CrCl was defined as more than 10 mL/minute difference between CrClactual and CrClcalculated. Results: We included 107 patients with advanced cancers who had 24-hour urine creatinine assessments. The concordance correlation coefficient between CrClactual and CrClcalculated was 0.423 (95% CI: 0.271–0.555). The CGF underestimated CrCl in 33% of patients (n=35). In 21 patients who had CrClcalculated of less than 60 mL/minute, the CrClactual was more than 60 mL/minute in 7 patients (33%). In 7 patients who had CrClcalculated of less than 45 mL/minute, the CrClactual was more than 45 mL/minute in 2 patients (29%). Conclusions: The low concordance between CrClactual and CrClcalculated suggests a weak agreement and notable variability. Restricting clinical trial enrollment to patients with CrClcalculated above certain cutoffs would disqualify nearly one third of patients with normal CrCl. Clinical trial eligibility criteria should allow for estimation of CrCl using 24-hour urine collection especially in patients not meeting inclusion criteria based on CGF or other equations alone. Citation Format: Mohamed A. Gouda, Lei Kang, Tin-Yun Tang, Ecaterina E. Dumbrava, Stephane Champiat, Sarina A. Piha-Paul, Paula R. Pohlmann, Aung Naing, Siqing Fu, Apostolia M. Tsimberidou, Jordi Rodon, Timothy A. Yap, Funda Meric-Bernstam, David S. Hong. Discrepancies Between Calculated and Actual Creatinine Clearance: A Phase 1 Trial Unit Experience [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C063.