High-dose carboplatin and regimen-related toxicity following autologous bone marrow transplant
High-dose carboplatin and regimen-related toxicity following autologous bone marrow transplant
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DOI：
10.1038/sj.bmt.1703417
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发表时间：
2002-03-01
影响因子：
4.8
通讯作者：
Spitzer, TR
中科院分区：
文献类型：
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作者：
Colby, C;Koziol, S;Spitzer, TR
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）而不是体表面积（BSA）时，毒性预测更准确。我们回顾性计算了117例接受自体干细胞移植的患者的卡铂AUC，这些患者接受了由卡铂1800 mg/m2和环磷酰胺6000 mg/m2组成的预处理方案，以确定较高的卡铂暴露是否导致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。20例（17%）患者发生了额外的大于或等于2级的毒性，特别是肾毒性，与较高的中位AUC 10.2 mg/ml（-1）min显著相关（P = 0.001）。既往铂类药物治疗也与毒性显著相关（P = 0.052）。虽然基于BSA的卡铂剂量变化极小（中位数990（范围450-1340）mg），但计算的AUC显示接近4倍的暴露范围（中位数7.8（范围3.6 - 13.8）mg/ml（-1）min）。这些数据表明非血液学不良事件与AUC估计值之间存在相关性。前瞻性试验将是必要的，以确定目标卡铂AUC，优化结果和最大限度地减少毒性，在自体移植设置。
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 greater than or equal tograde 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 nonhematologic 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.