Colby C, Koziol S, McAfee S L, Yeap B, Spitzer T R
Bone Marrow Transplantation Program/Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Bone Marrow Transplant. 2002 Mar;29(6):467-72. doi: 10.1038/sj.bmt.1703417.
Pharmacokinetic analysis of carboplatin dosing suggests a more accurate prediction of toxicity when the dose is based on the area under the plasma concentration vs time curve (AUC) instead of body surface area (BSA). We retrospectively calculated the carboplatin AUC of 117 patients who received an autologous stem cell transplant following a conditioning regimen consisting of carboplatin 1800 mg/m(2) and cyclophosphamide 6000 mg/m(2) to identify whether higher carboplatin exposure resulted in an increase in regimen-related non-hematologic toxicities. The most common non-hematologic toxicities were gastrointestinal and hepatic. Twenty (17%) patients experienced additional > or =grade 2 toxicity, specifically, renal toxicity significantly associated with a higher median AUC of 10.2 mg/ml(-1) min (P = 0.001). Prior platinum therapy was also significantly associated with toxicity (P = 0.052). While carboplatin dose based on BSA varied minimally (median 990 (range 450-1340) mg, the calculated AUC showed a near four-fold range of exposure (median 7.8 (range 3.6 to 13.8) mg/ml(-1) min). These data suggest a relationship between non-hematologic adverse events and the estimated AUC. Prospective trials will be necessary to identify the target carboplatin AUC which optimizes outcome and minimizes toxicity in the autologous transplant setting.
卡铂给药的药代动力学分析表明，当剂量基于血浆浓度-时间曲线下面积（AUC）而非体表面积（BSA）时，对毒性的预测更准确。我们回顾性计算了117例接受自体干细胞移植患者的卡铂AUC，这些患者在预处理方案中接受了1800mg/m²卡铂和6000mg/m²环磷酰胺，以确定更高的卡铂暴露量是否会导致与方案相关的非血液学毒性增加。最常见的非血液学毒性是胃肠道和肝脏毒性。20例（17%）患者出现额外的≥2级毒性，具体而言，肾毒性与更高的中位AUC 10.2mg/ml⁻¹min显著相关（P = 0.001）。既往铂类治疗也与毒性显著相关（P = 0.052）。虽然基于BSA的卡铂剂量变化最小（中位值990（范围450 - 1340）mg），但计算出的AUC显示暴露范围接近四倍（中位值7.8（范围3.6至13.8）mg/ml⁻¹min）。这些数据表明非血液学不良事件与估计的AUC之间存在关联。有必要进行前瞻性试验，以确定在自体移植环境中优化结局并使毒性最小化的目标卡铂AUC。
