Oncology/Haematology, Kantonsspital Graubünden, Chur
SAKK (Swiss Group for Clinical Cancer Research) Coordinating Centre, Berne, Switzerland.
Ann Oncol. 2014 Aug;25(8):1591-7. doi: 10.1093/annonc/mdu129. Epub 2014 Mar 25.
Seminoma stage I is the most frequent testis cancer and single-dose carboplatin (AUC7) is an effective and widely used adjuvant treatment. Underdosing of carboplatin by 10% has been shown to almost double the rate of relapse and hence correct dosing based on accurate GFR measurement is crucial. The gold standard of GFR measurement with a radiolabelled isotope is expensive and not readily available. In many institutions, it is replaced by GFR estimation with the Cockcroft-Gault formula, which might lead to significant carboplatin underdosing and potentially inferior clinical outcome.
Retrospective analysis of all patients with stage I seminoma treated with adjuvant carboplatin between 1999 and 2012. All patients had serum creatinine measured and underwent GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI, Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy. Bias, precision, rates of under- and overdosing of GFR estimates were compared with measured GFR. Bland-Altman plots were done.
A total of 426 consecutive Caucasian male patients were included: median age 39 years (range 19-60 years), median measured GFR 118 ml/min (51-209), median administered carboplatin dose 1000 mg (532-1638). In comparison to isotopic GFR measurement, a relevant proportion of patients would have received ≤ 90% of carboplatin dose through the use of GFR estimation formulae: 4% using Mayo, 9% Martin, 18% Cockcroft-Gault, 24% Wright, 63% Jelliffe, 49% MDRD and 41% using 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.
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.
精原细胞瘤 I 期是最常见的睾丸癌，单次剂量卡铂（AUC7）是一种有效且广泛使用的辅助治疗方法。已有研究表明，卡铂剂量减少 10%会使复发率几乎翻倍，因此基于准确的肾小球滤过率（GFR）测量进行正确的剂量给药至关重要。使用放射性标记同位素进行 GFR 测量是金标准，但该方法既昂贵又不易获得。在许多机构中，它被 Cockcroft-Gault 公式进行 GFR 估计所取代，这可能导致卡铂剂量显著不足，并可能导致临床结局不佳。
对 1999 年至 2012 年间接受辅助性卡铂治疗的 I 期精原细胞瘤患者进行回顾性分析。所有患者均测量血清肌酐，并进行放射性同位素（51Cr-EDTA 或 99mTc-DTPA）GFR 测量，同时与 7 种标准 GFR 估算公式（Cockcroft-Gault、CKD-EPI、Jelliffe、Martin、Mayo、MDRD 和 Wright）和一种固定剂量策略进行比较。比较 GFR 估计值的偏倚、精密度、低估和高估率与实测 GFR。进行 Bland-Altman 图分析。
共纳入 426 例连续的白种男性患者：中位年龄 39 岁（19-60 岁），中位实测 GFR 为 118ml/min（51-209），中位卡铂给药剂量为 1000mg（532-1638）。与同位素 GFR 测量相比，通过使用 GFR 估算公式，相当一部分患者的卡铂剂量将减少至≤90%：Mayo 为 4%、Martin 为 9%、Cockcroft-Gault 为 18%、Wright 为 24%、Jelliffe 为 63%、MDRD 为 49%和 CKD-EPI 为 41%。固定剂量策略、Wright 和 Cockcroft-Gault 公式的平均百分比误差最小，分别为+1.9%、+0.4%和+2.1%。
使用 Cockcroft-Gault 或任何其他公式进行 GFR 估计会导致相当一部分 I 期精原细胞瘤患者的辅助性卡铂剂量不足，不应将其视为标准治疗方法。
