Hijiya Nobuko, Panetta John C, Zhou Yinmei, Kyzer Emily P, Howard Scott C, Jeha Sima, Razzouk Bassem I, Ribeiro Raul C, Rubnitz Jeffrey E, Hudson Melissa M, Sandlund John T, Pui Ching-Hon, Relling Mary V
Department of Oncology, St Jude Children's Research Hospital, 332 North Lauderdale St, Memphis, TN 38105-2794, USA.
Blood. 2006 Dec 15;108(13):3997-4002. doi: 10.1182/blood-2006-05-024414. Epub 2006 Aug 17.
There is conflicting information about the influence of body mass index (BMI) on the pharmacokinetics, toxicity, and outcome of chemotherapy. We compared pharmacokinetics, outcome, and toxicity data across 4 BMI groups (underweight, BMI < or = 10th percentile; normal; at risk of overweight, BMI > or = 85th and < 95th percentile; overweight, BMI > or = 95th percentile) in 621 children with acute lymphoblastic leukemia (ALL) treated on 4 consecutive St Jude Total Therapy studies. Chemotherapy doses were not adjusted to ideal BMI. Estimates of overall survival (86.1% +/- 3.4%, 86.0% +/- 1.7%, 85.9% +/- 4.3%, and 78.2% +/- 5.5%, respectively; P = .533), event-free survival (76.2% +/- 4.2%, 78.7% +/- 2.1%, 73.4% +/- 5.5%, and 72.7% +/- 5.9%, respectively; P = .722), and cumulative incidence of relapse (16.0% +/- 3.7%, 14.4% +/- 1.8%, 20.6% +/- 5.1%, and 16.7% +/- 5.1%, respectively; P = .862) did not differ across the 4 groups. In addition, the intracellular levels of thioguanine nucleotides and methotrexate polyglutamates did not differ between the 4 BMI groups (P = .73 and P = .74, respectively). The 4 groups also did not differ in the overall incidence of grade 3 or 4 toxicity during the induction or postinduction periods. Further, the systemic clearance of methotrexate, teniposide, etoposide, and cytarabine did not differ with BMI (P > .3). We conclude that BMI does not affect the outcome or toxicity of chemotherapy in this patient population with ALL.
关于体重指数(BMI)对化疗的药代动力学、毒性及疗效的影响,存在相互矛盾的信息。我们比较了连续4项圣裘德全疗程治疗研究中接受治疗的621例急性淋巴细胞白血病(ALL)儿童患者的药代动力学、疗效及毒性数据,这些患者分属4个BMI组(体重过轻,BMI≤第10百分位数;正常;超重风险,BMI≥第85百分位数且<第95百分位数;超重,BMI≥第95百分位数)。化疗剂量未根据理想BMI进行调整。总生存率估计值(分别为86.1%±3.4%、86.0%±1.7%、85.9%±4.3%和78.2%±5.5%;P = 0.533)、无事件生存率(分别为76.2%±4.2%、78.7%±2.1%、73.4%±5.5%和72.7%±5.9%;P = 0.722)及累积复发率(分别为16.0%±3.7%、14.4%±1.8%、20.6%±5.1%和16.7%±5.1%;P = 0.862)在4组间无差异。此外,4个BMI组间硫鸟嘌呤核苷酸和甲氨蝶呤多聚谷氨酸的细胞内水平无差异(分别为P = 0.73和P = 0.74)。4组在诱导期或诱导后期3级或4级毒性的总发生率上也无差异。此外,甲氨蝶呤、替尼泊苷、依托泊苷和阿糖胞苷的全身清除率与BMI无关(P>0.3)。我们得出结论,在该ALL患者群体中,BMI不影响化疗的疗效或毒性。