Ratto G B, Civalleri D, Esposito M, Spessa E, Alloisio A, De Cian F, Vannozzi M O
Istituto Anatomia Chirurgica and Istituto Clinica Chirurgica, University of Genoa, Istituto Nazionale per la Ricerca sul Cancro, Servizio di Farmacologia Tossicologica, Genoa, Italy.
J Thorac Cardiovasc Surg. 1999 Apr;117(4):759-65. doi: 10.1016/S0022-5223(99)70297-7.
Malignant pleural mesothelioma is an ideal model for testing new locoregional multimodality approaches because of its aggressive local behavior.
This study was planned to investigate the feasibility, safety, and pharmacokinetics of a multimodality therapy including an operation, pleural space perfusion (60 minutes) with cisplatin (100 mg/m2), hyperthermia (41. 5 degrees C), and postoperative radiotherapy (55 Gy to chest wall incisions). The effects of the extent of resection and perfusion temperature on cisplatin pharmacokinetics were evaluated. Ten patients with epithelial or mixed, stage I or II, malignant pleural mesothelioma underwent the following procedures: group A (3 patients), pleurectomy/decortication and normothermic pleural space antineoplastic perfusion; group B (3 patients), pleurectomy/decortication and hyperthermic perfusion; and group C (4 patients), pleuropneumonectomy and hyperthermic perfusion. Operations were selectively applied depending on tumor extent. Platinum levels were serially measured by atomic absorption in systemic blood, perfusate, lung, and endothoracic fascia.
The overall procedure was completed in every case, without any death or toxicity. No lung damage was demonstrated after treatment. Major complications included 1 wound infection and 1 diaphragmatic prosthesis displacement. The mean peak platinum plasma levels were reached within 45 to 60 minutes after perfusion was started. Systemic drug concentrations were greater after pleurectomy/decortication than after pleuropneumonectomy (P =.006). The local tissue/perfusate ratio of platinum concentrations tended to be higher after hyperthermic perfusion rather than normothermic perfusion.
This multimodality approach is feasible, pharmacokinetically advantageous, and safe enough to undergo further clinical investigations.
恶性胸膜间皮瘤因其具有侵袭性的局部行为，是测试新的局部多模态治疗方法的理想模型。
本研究旨在调查一种多模态治疗的可行性、安全性和药代动力学，该治疗包括手术、顺铂（100mg/m²）胸膜腔灌注（60分钟）、热疗（41.5摄氏度）和术后放疗（胸壁切口处55Gy）。评估切除范围和灌注温度对顺铂药代动力学的影响。10例上皮型或混合型、I期或II期恶性胸膜间皮瘤患者接受了以下手术：A组（3例患者），胸膜剥脱术/去皮质术和常温胸膜腔抗肿瘤灌注；B组（3例患者），胸膜剥脱术/去皮质术和热灌注；C组（4例患者），胸膜肺切除术和热灌注。根据肿瘤范围选择性地进行手术。通过原子吸收法连续测量全身血液、灌注液、肺和胸内筋膜中的铂水平。
每例患者均完成了整个手术过程，无死亡或毒性反应。治疗后未发现肺损伤。主要并发症包括1例伤口感染和1例膈肌假体移位。灌注开始后45至60分钟内达到铂血浆平均峰值水平。胸膜剥脱术/去皮质术后的全身药物浓度高于胸膜肺切除术后（P = 0.006）。热灌注后铂浓度的局部组织/灌注液比值往往高于常温灌注。
这种多模态治疗方法是可行的，在药代动力学方面具有优势，并且足够安全，可以进行进一步的临床研究。
