Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer.
Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer.
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DOI：
10.1248/bpb.29.1441
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发表时间：
2006-07
影响因子：
2
通讯作者：
Eriko Sato;I. Yano;Mari Jiko;Kazushige Takahashi;Hideyuki Motohashi;S. Masuda;T. Katsura;H. Nishiyama;T. Segawa;N. Ito;T. Kamoto;O. Ogawa;K. Inui
中科院分区：
文献类型：
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作者：
Eriko Sato;I. Yano;Mari Jiko;Kazushige Takahashi;Hideyuki Motohashi;S. Masuda;T. Katsura;H. Nishiyama;T. Segawa;N. Ito;T. Kamoto;O. Ogawa;K. Inui
对于激素难治性前列腺癌，紫杉醇和卡铂的联合治疗有望延长生命。我们研究了卡铂在日本前列腺癌患者(n=10，55-72岁)中的药代动力学，并评价了卡尔弗特公式在个体化剂量调整中的作用。在静脉注射紫杉醇(175 mg/m(2))后，静注卡铂(自由血药浓度-时间曲线下面积=5 mg·min/ml)。每名患者的卡铂剂量根据Calvert公式使用个人肌酐清除值来确定。连续测定每例患者的血浆总铂浓度，测定卡铂的药代动力学参数。静脉滴注总卡铂后的血药浓度符合二室模型。卡铂清除量为62.0+/-12.7ml/min(平均+/-S.D.)，且与个体肌酐清除量呈线性相关(r(2)=0.64，p<；0.01)。卡铂的实际AUC为8.20+/-1.11mg.min/ml，其个体间变异降至卡铂清除量的65%，表明Calvert公式用于卡铂剂量调整是有效的。根据国家癌症研究所的共同毒性标准，在一名患者中发现了4级白细胞减少，但没有患者表现出血小板减少。总之，根据卡尔弗特公式确定卡铂剂量，与卡铂清除相比，实际AUC中的个体间变异性降低，对于日本前列腺癌患者来说，卡铂5毫克·分/毫升的目标AUC是相对安全的。
For hormone refractory prostate carcinoma, a combination therapy of paclitaxel and carboplatin is used to expect life extension. We investigated the pharmacokinetics of carboplatin in Japanese prostate cancer patients (n=10, 55-72 years), and evaluated the usefulness of Calvert's formula in the individualized dosing adjustment. They were intravenously administered carboplatin (area under the free plasma concentration versus time curve (AUC)=5 mg.min/ml), following the intravenous administration of paclitaxel (175 mg/m(2)). The dosage of carboplatin for each patient was determined with Calvert's formula using individual creatinine clearance values. Plasma concentration of total platinum was measured sequentially and the pharmacokinetic parameters of carboplatin were determined in each patient. Plasma concentration of total carboplatin after intravenous infusion well fitted the two-compartment model. Carboplatin clearance was 62.0+/-12.7 ml/min (mean+/-S.D.), and linearly related to the individual creatinine clearance (r(2)=0.64, p<0.01). The actual AUC for total carboplatin was 8.20+/-1.11 mg.min/ml, and its inter-individual variability was decreased to 65% of that in carboplatin clearance, indicating the effectiveness of Calvert's formula for dosage adjustment of carboplatin. Leucopenia of grade 4 according to the National Cancer Institute's Common Toxicity Criteria was found in one patient, but no patient demonstrated thrombocytopenia. In conclusion, determining carboplatin dosage based on Calvert's formula decreased the inter-individual variability in the actual AUC compared with that in the carboplatin clearance, and a target AUC of 5 mg.min/ml of carboplatin was comparatively safe for Japanese patients with prostate cancer.