Morrow Amy, Garland Campbell, Yang Fei, De Luna Mike, Herrington Jon D
1 Baylor Scott & White Medical Center, Temple, TX, USA.
2 The University of Texas at Austin College of Pharmacy, Austin, TX, USA.
J Oncol Pharm Pract. 2019 Oct;25(7):1651-1657. doi: 10.1177/1078155218805136. Epub 2018 Oct 18.
The use of the Calvert formula to calculate carboplatin doses allows clinicians to achieve the appropriate carboplatin area under the concentration (AUC) curve. Thrombocytopenia is the dose limiting toxicity of carboplatin and optimizing AUC minimizes the risk of thrombocytopenia. Carboplatin clearance directly correlates with glomerular filtration rate (GFR) and, therefore, an accurate estimation of the renal function is needed. The Calvert formula was designed using the GFR measured by Cr-EDTA; however, many clinicians substitute estimated creatinine clearance (CrCl) as calculated by the Cockcroft-Gault (C-G) equation. The potential for overestimating AUC occurs when clinicians substitute actual weight in obese patients or use a low serum creatinine when calculating C-G estimated CrCl. In 2010, the National Cancer Institute recommended the GFR value within the Calvert formula should not exceed 125 mL/min, thereby capping the carboplatin dose. However, there are studies demonstrating that certain patients' actual GFR values do exceed 125 mL/min. Therefore, capping the carboplatin dose in these patients may lead to underestimating the carboplatin AUC. A single-center, retrospective study was performed to evaluate the change in platelet count pre- and post-carboplatin exposure in patients with C-G estimated CrCl greater than 125 mL/min receiving capped versus uncapped carboplatin doses. A review of carboplatin dosing strategies is also presented. This study indicated there was a larger mean difference in pre- and post-platelet count in patients receiving uncapped carboplatin compared to patients receiving capped carboplatin with no differences in toxicities. Dose capping this patient population will likely lead to a lower AUC rather than the intended AUC target, which could ultimately lead to substandard outcomes.
使用卡尔弗特公式计算卡铂剂量可使临床医生实现合适的卡铂浓度-时间曲线下面积(AUC)。血小板减少是卡铂的剂量限制性毒性,优化AUC可将血小板减少的风险降至最低。卡铂清除率与肾小球滤过率(GFR)直接相关,因此需要准确估算肾功能。卡尔弗特公式是使用Cr-EDTA测量的GFR设计的;然而,许多临床医生用Cockcroft-Gault(C-G)方程计算的估计肌酐清除率(CrCl)来替代。当临床医生在肥胖患者中使用实际体重或在计算C-G估计CrCl时使用低血清肌酐时,存在高估AUC的可能性。2010年,美国国立癌症研究所建议卡尔弗特公式中的GFR值不应超过125 mL/min,从而限制卡铂剂量。然而,有研究表明某些患者的实际GFR值确实超过125 mL/min。因此,对这些患者限制卡铂剂量可能会导致低估卡铂AUC。进行了一项单中心回顾性研究,以评估C-G估计CrCl大于125 mL/min的患者在接受限制剂量与非限制剂量卡铂前后血小板计数的变化。还介绍了卡铂给药策略的综述。这项研究表明,与接受限制剂量卡铂的患者相比,接受非限制剂量卡铂的患者血小板计数前后的平均差异更大,且毒性无差异。对这一患者群体进行剂量限制可能会导致较低的AUC,而不是预期的AUC目标,这最终可能导致治疗效果不佳。