Abstract
Carboplatin clearance is correlated with glomerular filtration rate (GFR) and usually estimated with creatinine clearance using Cockcroft-Gault (CG) formula. Because plasma creatinine level is highly correlated with muscle mass, we hypothesized that an abnormal body composition with a low lean body mass (LBM) percentage [(LBM/weight)×100]may result in inadequate carboplatin dosing. Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We aimed to investigate the influence of total LBM and LBM percentage on GFR calculation, using creatinine (CrCl) or cystatin C (GFRcysC-creat) in cancer patients. Pretreatment serum creatinine and cystatin C were prospectively measured in consecutive patients. CrCl (CG formula), GFRcysC-creat (CKD-EPI creatinine-cystatin equation), and LBM (CT scan) were calculated. Severe thrombocytopenia post-carboplatin were analyzed. In 131 patients without renal insufficiency, LBM was correlated with creatinine (r=0.30, p<0.005) but not with cystatin C (r=-0.07, p=0.43). In patients with the lowest LBM percentage, the CrCl was significantly higher than GFRcysC-creat indicating an overestimation of GFR with creatinine (p=0.0004). In 24 patients treated with carboplatin AUC 5 (mg/mlmin)±paclitaxel, the risk of severe thrombocytopenia was associated with lower LBM percentage (p=0.0002) and higher CrCl/GFRcysC-creat ratio (p=0.006). By ROC analysis, the CrCl/GFRcysC-creat ratio threshold predicting severe thrombocytopenia was 1.23. A low LBM percentage increases the risk of inadequate GFR calculation by CG formula, and carboplatin overdosage with severe thrombocytopenia. High CrCl/GFRcysC-creat ratio allows the identification of these patients.
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