Relevant risk of Carboplatin underdosing in cancer patients with normal renal function using estimated GFR: Lessons from a stage I Seminoma cohort

We conducted a retrospective cohort analysis in order to co mpare the actual GFR measured by radioisotope methods with different formulae for the estimation of GFR (eGFR) and a flat dosing strategy in patients with seminoma stage I and to assess their impact on potential underdosing: 426 patients with stage I seminoma up to the age of 60 ye ars treated with adjuvant carboplatin over a period of 12 years. In comparison to radioisotopic GFR measurement, a relevant proportion of patients would have received ≤ 90% of carboplatin dose through the use of eGFR formulae: 4% using Mayo, 9% Martin, 18% Cockcroft‐Gault, 24% Wright, 63% Jelliffe, 49% MDRD and 41% usi ng CKD‐EPI. The flat dosing strategy, Wright and Cockcroft‐Gault formulae showed the smallest bias with mean percentage error of +1.9, +0.4 and +2.1, respectively. Subgroup analyses showed that if the Cockcroft‐Gault formula was used for Carboplatin dosing, patients aged 40 – 59 years or with BMI 20 – 25 woul d be at the highest risk for underdosing. As a conclusion, using Cockcroft‐Gault or any other formula for GFR estimation leads to underdosing of adjuvant carboplatin in a relevant number of patients with seminoma stage I and should not be regarded as standard of care. Oncologists treating y oung patients with normal renal function with carboplatin must be aware of these limitations of the formulae for GFR estimation. Consequently, radioisotope measurement of GFR is recommended unless improvements of dosing algorithms are achieved for the use in settings and health systems where GFR measurement is impossible."