Purpose
In 2022, The International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) recommended utilising measured glomerular filtration rate (mGFR) or body surface area-adjusted estimated glomerular filtration rate (BSA-adjusted eGFR) instead of creatinine clearance (CrCl) for carboplatin dosing1. This study evaluated the real-world impact of implementing these guidelines.
Methods
A retrospective analysis was conducted on adult patients (n=218) who received carboplatin at a tertiary referral hospital in Sydney, Australia. Doses calculated using CrCl and BSA-adjusted eGFR were compared, with a ≥10% discordance considered clinically significant. After excluding patients with upfront dose reductions, toxicity incidence was assessed in pre-ADDIKD (n=99) and post-ADDIKD (n=108) cohorts. Statistical analyses included chi-square, Fisher's exact, and Mann-Whitney U.
Results
Patients with clinically significant dose discordance was associated with age and body size. Higher BSA-adjusted eGFR-based doses were observed in older, smaller patients (median age 74 vs 65 years, p<0.0001; median BMI 21.4 vs 26.2 kg/m², p<0.0001), while lower doses were seen in younger, larger patients (median age 56 vs 65 years, p=0.0024; median BMI 31.5 vs 26.2 kg/m², p=0.0002). Compared to CrCl, BSA-adjusted eGFR dosing was associated with significantly lower toxicity rates (RR 0.38, 95% CI: 0.18–0.83, p=0.0096). Subgroup analysis, including mGFR, showed significant toxicity differences across dosing methods (Fisher’s exact p=0.018) with lower toxicity using BSA-adjusted eGFR vs CrCl (p=0.015), and mGFR vs BSA-adjusted eGFR (p=0.011). While treatment regimen distributions differed between the two groups (p=0.036), this was determined as not statistically significant in causing toxicity reduction in the post-ADDIKD group.
Conclusion
Toxicity reduction following ADDIKD implementation is most likely attributable to the shift in carboplatin dosing methodology. These findings support adopting BSA-adjusted eGFR as standard, with mGFR offering further benefit in select patients. Larger multi-centre studies are warranted.