J Clin Oncol. 2023 Oct 1;41(28):4453-4454. doi: 10.1200/JCO.22.02768.
A dosage formula has been derived from a retrospective analysis of carboplatin pharmacokinetics in 18 patients with pretreatment glomerular filtration rates (GFR) in the range of 33 to 136 mL/min. Carboplatin plasma clearance was linearly related to GFR (r = 0.85, P less than .00001) and rearrangements of the equation describing the correlation gave the dosage formula dose (mg) = target area under the free carboplatin plasma concentration versus time curve (AUC) x (1.2 x GFR + 20). In a prospective clinical and pharmacokinetic study the formula was used to determine the dose required to treat 31 patients (GFR range, 33 to 135 mL/min) with 40 courses of carboplatin. The target AUC was escalated from 3 to 8 mg carboplatin/mL/min. Over this AUC range the formula accurately predicted the observed AUC (observed/predicted ratio 1.24 +/- 0.11, r = 0.886) and using these additional data, the formula was refined. Dose (mg) = target AUC x (GFR + 25) is now the recommended formula. AUC values of 4 to 6 and 6 to 8 mg/mL. min gave rise to manageable hematological toxicity in previously treated and untreated patients, respectively, and hence target AUC values of 5 and 7 mg/mL min are recommended for single-agent carboplatin in these patient groups. Pharmacokinetic modeling demonstrated that the formula was reasonably accurate regardless of whether a one- or two-compartment model most accurately described carboplatin pharmacokinetics, assuming that body size did not influence nonrenal clearance. The validity of this assumption was demonstrated in 13 patients where no correlation between surface area and nonrenal clearance was found (r = .31, P = .30). Therefore, the formula provides a simple and consistent method of determining carboplatin dose in adults. Since the measure of carboplatin exposure in the formula is AUC, and not toxicity, it will not be influenced by previous or concurrent myelosuppressive therapy or supportive measures. The formula is therefore applicable to combination and high-dose studies as well as conventional single-agent therapy, although the target AUC for carboplatin will need to be redefined for combination chemotherapy.
已经从 18 例预处理肾小球滤过率（GFR）在 33 至 136mL/min 范围内的卡铂药代动力学的回顾性分析中得出剂量公式。卡铂血浆清除率与 GFR 呈线性相关（r = 0.85，P 小于 0.00001），并且对描述相关性的方程进行重新排列给出了剂量公式剂量（mg）=目标游离卡铂血浆浓度-时间曲线下面积（AUC）x（1.2 x GFR + 20）。在一项前瞻性临床和药代动力学研究中，该公式用于确定 31 例（GFR 范围 33 至 135mL/min）患者接受 40 个疗程卡铂治疗所需的剂量。目标 AUC 从 3 至 8mg 卡铂/mL/min 递增。在这个 AUC 范围内，公式准确地预测了观察到的 AUC（观察到的/预测的比值 1.24 +/- 0.11，r = 0.886），并使用这些额外的数据对公式进行了修正。现在推荐的公式为剂量（mg）=目标 AUC x（GFR + 25）。对于先前治疗和未治疗的患者，分别给予 AUC 值为 4 至 6 和 6 至 8mg/mL.min，可引起可管理的血液学毒性，因此，对于这些患者群体中的单药卡铂，建议目标 AUC 值为 5 和 7mg/mL.min。药代动力学模型表明，无论是否最准确地描述了卡铂药代动力学，使用一个或两个隔室模型，公式都具有相当的准确性，假设身体大小不影响非肾清除率。在 13 例患者中证明了这一假设的有效性，这些患者的表面积与非肾清除率之间没有相关性（r =.31，P =.30）。因此，该公式为成人确定卡铂剂量提供了一种简单而一致的方法。由于公式中卡铂暴露的度量是 AUC，而不是毒性，因此它不会受到先前或同时的骨髓抑制治疗或支持措施的影响。因此，该公式适用于联合和高剂量研究以及常规单药治疗，尽管需要为联合化疗重新定义卡铂的目标 AUC。
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