卡铂剂量在卵巢癌治疗中的应用：NRG 肿瘤学组研究。
Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study.
机构信息
Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America.
NRG Oncology Statistics and Data Center, Roswell Park Cancer Institute, Buffalo, NY, United States of America.
出版信息
Gynecol Oncol. 2023 Jul;174:213-223. doi: 10.1016/j.ygyno.2023.05.013. Epub 2023 May 23.
OBJECTIVE
To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl).
METHODS
Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event.
RESULTS
AUC statistics (range, 0.52-0.64) showed log(CrCl) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl <60 mL/min. Positive predictive values for adverse events ranged from 1.8%-15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively.
CONCLUSION
The formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl <60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl <60 mL/min as an exclusion criterion from clinical trials.
目的
确定使用美国国家综合癌症网络（NCCN）指南来估计肾功能对卡铂剂量的影响，并探讨更准确估计较低肌酐清除率（CrCl）相关的不良影响。
方法
我们回顾性分析了 GOG182 试验（NCT00011986）中的 3830 例患者（4312 例患者的 3830 例）的数据，该试验是一项铂类化疗治疗晚期卵巢癌的 III 期临床试验。GOG182 中的每位患者的卡铂剂量使用杰弗里公式确定。我们重新计算了 CrCl，以使用肾脏病膳食改良试验（MDRD）和 Cockcroft-Gault（有/无 NCCN 推荐的修改）公式来确定剂量。使用受试者工作特征曲线（ROC）下面积（AUC）描述了基线 CrCl 与毒性之间的关系。敏感性和阳性预测值描述了该模型在区分有无不良事件的受试者方面的能力。
结果
AUC 统计数据（范围 0.52-0.64）表明，CrCl 对数不是预测 3 级以上不良事件（贫血、血小板减少症、发热性中性粒细胞减少症、听觉、肾脏、代谢、神经病）的良好指标。在 3830 例患者中，有 628 例（16%）的 CrCl<60 mL/min。不良事件的阳性预测值范围为 1.8%-15%。使用 Cockcroft-Gault、Cockcroft-Gault 联合 NCCN 修正公式和 MDRD（而不是杰弗里公式）来估计肾功能，导致分别有 16%、32%和 5.2%的患者的卡铂剂量减少 10%以上，分别有 41%、9.6%和 12%的患者的卡铂剂量增加 10%以上。
结论
用于估计 CrCl 的公式会影响卡铂的剂量。（根据杰弗里公式）估计的 CrCl<60 mL/min 并不能准确预测不良事件。目前正在努力更好地预测肾功能。我们的数据不支持将 NCCN 倡议扩大研究资格作为临床试验的排除标准，因此不支持将 CrCl<60 mL/min 作为排除标准。
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