Calvert A H
Cancer Research Unit, University of Newcastle Upon Tyne, UK.
Semin Oncol. 1997 Feb;24(1 Suppl 2):S2-85-S2-90.
The combination of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been found to be highly active, to offer convenience of administration and better potential for dose escalation, and to produce less nonhematologic toxicity than standard therapy with cisplatin plus paclitaxel. Increased myelosuppression was anticipated to be a disadvantage of the carboplatin/paclitaxel combination, although it was expected to affect mainly platelets. Studies to date of the paclitaxel/carboplatin combination suggest the combination has a relatively benign effect on platelets compared with single-agent carboplatin. Previous pharmacokinetic studies have suggested that the measured area under the plasma carboplatin concentration-time curve is significantly less than that predicted by dosing formulas based on glomerular filtration rates. Newer evidence, however, contradicts these findings. This review examines the evidence of both a pharmacodynamic and a pharmacokinetic interaction between carboplatin and paclitaxel that has a sparing effect on platelets. It further assesses methodologic differences in methods used to estimate glomerular filtration. Paclitaxel appears to offer some protective effect for carboplatin-induced thrombocytopenia, although the two drugs do not interact pharmacokinetically. The apparent deviations of the achieved carboplatin area under the plasma concentration-time curve from that predicted by a dosing formula are thought to be due to differences in the methodology used to estimate renal function and measure creatinine. Any interaction between the two drugs most likely occurs at the level of the megakaryocyte.
已发现卡铂与紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）联合使用具有高效活性，给药方便且剂量递增潜力更大，与顺铂加紫杉醇的标准疗法相比，产生的非血液学毒性更小。虽然预计卡铂/紫杉醇联合使用会增加骨髓抑制，且预计主要影响血小板，但迄今为止对紫杉醇/卡铂联合使用的研究表明，与单药卡铂相比，该联合用药对血小板的影响相对较小。先前的药代动力学研究表明，血浆卡铂浓度-时间曲线下的实测面积显著小于基于肾小球滤过率的给药公式所预测的面积。然而，最新证据与这些发现相矛盾。本综述考察了卡铂和紫杉醇之间存在对血小板有保护作用的药效学和药代动力学相互作用的证据。它还进一步评估了用于估计肾小球滤过的方法在方法学上的差异。紫杉醇似乎对卡铂诱导的血小板减少有一定保护作用，尽管这两种药物在药代动力学上不相互作用。血浆浓度-时间曲线下实测的卡铂面积与给药公式预测值之间的明显偏差被认为是由于用于估计肾功能和测量肌酐的方法不同所致。这两种药物之间的任何相互作用很可能发生在巨核细胞水平。
