Bouligand J, Boland I, Valteau-Couanet D, Deroussent A, Kalifa C, Hartmann O, Vassal G
UPRES EA3535, Pharmacology and New Treatments of Cancers, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif 94800, France.
Bone Marrow Transplant. 2003 Nov;32(10):979-86. doi: 10.1038/sj.bmt.1704275.
A strong relationship has been demonstrated between high systemic exposure to busulfan and the occurrence of hepatic veno-occlusive disease (HVOD) after a busulfan-cyclophosphamide regimen (BU CY). We report a prospective study aimed at exploring the pharmacodynamics of high-dose busulfan combined with either melphalan (BU MEL) or thiotepa (BU TTP) followed by autologous stem cell transplantation in children and adolescents with a malignant solid tumor. Busulfan was given orally at a total dose of 600 mg m(-2). In all, 45 patients with a median age of 6.3 years were included in the study: 25 received BU MEL and 20 received BU TTP. The incidence of HVOD was 44% (CI 95% [23-65%]) in the BU MEL group and 25% (CI95% [9-49%]) in the BU TTP group. In the BU TTP group, patients who developed HVOD had a significantly higher AUC 0-6 h after the 13th dose (6201+/-607 h ng ml(-1)) than those who did not (5024+/-978 h ng ml(-1)) (P<0.05). In the BU MEL group, there was no difference in terms of systemic exposure to busulfan between patients who developed HVOD and those who did not. In conclusion, the guidelines established for monitoring BU CY cannot be extrapolated when busulfan is combined with another drug.
已证明在白消安 - 环磷酰胺方案（BU CY）后，高全身暴露于白消安与肝静脉闭塞性疾病（HVOD）的发生之间存在密切关系。我们报告了一项前瞻性研究，旨在探讨高剂量白消安联合美法仑（BU MEL）或塞替派（BU TTP），随后对患有恶性实体瘤的儿童和青少年进行自体干细胞移植的药效学。白消安口服给药，总剂量为600 mg m(-2)。该研究共纳入45例中位年龄为6.3岁的患者：25例接受BU MEL，20例接受BU TTP。BU MEL组HVOD的发生率为44%（95%置信区间[23 - 65%]），BU TTP组为25%（95%置信区间[9 - 49%]）。在BU TTP组中，发生HVOD的患者在第13剂后0 - 6小时的AUC显著高于未发生HVOD的患者（6201±607 h ng ml(-1)对5024±978 h ng ml(-1)）（P<0.05）。在BU MEL组中，发生HVOD的患者与未发生HVOD的患者在白消安全身暴露方面无差异。总之，当白消安与另一种药物联合使用时，不能外推用于监测BU CY所制定的指南。
