Leger-Enreille A, Cure H, Pezet D, Bargnoux P J
Laboratoire de Biochimie et Pharmacocinétique, Centre Jean Perrin, Clermont Fd., France.
Anticancer Res. 1994 Nov-Dec;14(6A):2327-9.
A chemotherapy using carboplatin, cisplatin and 5-fluorouracil in continuous infusion for advanced oesophageal cancer showed a high response rate in a previous feasibility study. The overall CT-scan response rate of 85% was obtained with a haematological dose-limiting toxicity: neutropenia and thrombopenia grade 3-4 of 23% and 30% respectively. In order to correlate myelosuppression with pharmacokinetic parameters, a pharmacological study was undertaken. The area under curve (AUC) of ultrafiltrable platinum and the residual rate of total platinum in 16 patients were tested. The measured creatinine clearance was found to be predictive of the subsequent myelosuppression. Plasma samples were using daily using the atomic absorption spectrometry technique. A strong relationship in individual patients was underlined between the AUC of ultrafiltrable platinum or residual rate of total platinum and the lowest platelet count for the first 3 days of treatment (p < 0.05). Conversely, the threshold value of the AUC at day one and residual rate at days two and three were calculated to prevent a highly probable haematotoxicity. Therefore, an optimal dose of carboplatin is determined in relation to the renal function of each patient.
在一项先前的可行性研究中，使用卡铂、顺铂和5-氟尿嘧啶持续输注治疗晚期食管癌的化疗方案显示出较高的缓解率。总体CT扫描缓解率为85%，血液学剂量限制性毒性为：3-4级中性粒细胞减少症和血小板减少症分别为23%和30%。为了将骨髓抑制与药代动力学参数相关联，开展了一项药理学研究。对16例患者的可超滤铂的曲线下面积（AUC）和总铂的残留率进行了检测。发现测得的肌酐清除率可预测随后的骨髓抑制。每天使用原子吸收光谱技术采集血浆样本。在个体患者中，可超滤铂的AUC或总铂的残留率与治疗前3天的最低血小板计数之间存在密切关系（p<0.05）。相反，计算第1天的AUC阈值以及第2天和第3天的残留率阈值，以预防极有可能发生的血液毒性。因此，根据每位患者的肾功能确定卡铂的最佳剂量。
