Lerza R, Esposito M, Vannozzi M, Bottino G B, Bogliolo G, Pannacciulli I
Department of Internal Medicine, University of Genoa, Italy.
Cancer. 1994 Jan 1;73(1):79-84. doi: 10.1002/1097-0142(19940101)73:1<79::aid-cncr2820730115>3.0.co;2-0.
The authors report a feasibility study of intrapleural cisplatin in a patient with inoperable malignant pleural mesothelioma.
Total and filterable platinum in pleural effusion and in plasma were monitored for two intrapleural courses of 120 mg/m2 cisplatin, and a weekly schedule was adopted. Platinum concentrations in pleural effusion, plasma, and urine were determined by flameless atomic absorption spectroscopy.
A lower peak of filterable platinum in plasma, a decrease in systemic filterable platinum exposure (AUC [area under the concentration-time curve]), and a greater pleural exposure to filterable platinum were observed after Course 2 compared with Course 1. After the second cycle of intrapleural treatment, the systemic AUC for filterable platinum was reduced by 40%.
The authors' findings may have some implications for the clinical use of intrapleural chemotherapy with high doses of cisplatin. Both infusions of cisplatin were generally well tolerated by the patient and were associated with the local pharmacologic advantage of sustained exposure to cisplatin of the pleural cavity. No sign of myelosuppression, neuropathy, or ototoxicity was observed, and acute toxicity consisted of mild nausea, vomiting, and prolonged anorexia. A transient presence of granular casts was the only observed nephrotoxic effect of cisplatin. Excellent local control of the disease with absence of recurrence of the effusion was observed.
作者报告了一项关于顺铂胸腔内注射治疗无法手术的恶性胸膜间皮瘤患者的可行性研究。
在两个疗程的120mg/m²顺铂胸腔内注射过程中，监测胸腔积液和血浆中的总铂和可滤过铂，并采用每周一次的给药方案。通过无火焰原子吸收光谱法测定胸腔积液、血浆和尿液中的铂浓度。
与第1疗程相比，第2疗程后血浆中可滤过铂的峰值降低，全身可滤过铂暴露量（浓度-时间曲线下面积[AUC]）减少，胸腔对可滤过铂的暴露增加。胸腔内治疗的第二个周期后，可滤过铂的全身AUC降低了40%。
作者的研究结果可能对高剂量顺铂胸腔内化疗的临床应用有一定启示。患者对两次顺铂输注的耐受性一般良好，且与胸腔持续暴露于顺铂的局部药理学优势有关。未观察到骨髓抑制、神经病变或耳毒性的迹象，急性毒性表现为轻度恶心、呕吐和长期厌食。顺铂唯一观察到的肾毒性作用是短暂出现颗粒管型。观察到疾病得到了良好的局部控制，胸腔积液未复发。
