Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
J Thorac Cardiovasc Surg. 2011 Jan;141(1):65-71. doi: 10.1016/j.jtcvs.2010.09.032.
Our objective was to evaluate whether platinum concentrations in chest wall tissue and in serum are optimized by intracavitary application of cisplatin loaded to a fibrin carrier compared with cisplatin solution in a randomized setting of a pig model.
After left-sided pneumonectomy including parietal pleurectomy, pigs were randomly assigned to receive either 90 mg/m(2) cisplatin intracavitary solution (n = 6) or to receive 5 mg cisplatin-fibrin (n = 5) applied on a predefined area of the chest wall. Platinum concentration in serum as well as in chest wall tissue was determined at several early time points until day 5 after treatment. Platinum levels were measured by inductively coupled plasma sector field mass spectrometric detection with a matrix-matched calibration procedure.
The dose- and surface-corrected (geometric) mean concentration of cisplatin in chest wall tissue 2 hours but also at day 5 after the application was doubled in animals treated with cisplatin-fibrin compared with the animals treated with cisplatin-solution. In serum, the dose- and surface-corrected exposure toward cisplatin (area under the curve(0-5d)) was significantly lower with cisplatin-fibrin than with cisplatin-solution (P < .0005). This is also reflected by significantly reduced serum creatinine and urea values in the cisplatin-fibrin group (P < .0001). Animals treated with cisplatin-fibrin additionally had a significantly better postoperative course as assessed by a well-being score (P < .001).
After cisplatin-fibrin treatment, cisplatin tissue concentration was increased whereas systemic cisplatin concentrations were significantly reduced in comparison with cisplatin-solution treatment. This finding offers a clear advantage inasmuch as rate and severity of systemic adverse events can be reduced while local cytotoxic concentrations are at least maintained.
本研究旨在评估与顺铂溶液相比，应用纤维蛋白载体制备的顺铂腔内给药能否优化胸壁组织和血清中的铂浓度，这是在猪模型中随机进行的一项研究。
在左侧全肺切除（包括壁层胸膜切除术）后，将猪随机分为两组，分别接受 90mg/m2顺铂腔内溶液（n=6）或 5mg 顺铂-纤维蛋白（n=5）应用于胸壁的预定区域。在治疗后直到第 5 天的几个早期时间点，分别测定血清和胸壁组织中的铂浓度。通过电感耦合等离子体质谱扇形场检测，并采用基质匹配校准程序测量铂水平。
与顺铂溶液组相比，接受顺铂纤维蛋白治疗的动物在 2 小时和治疗后第 5 天，胸壁组织中顺铂的剂量和表面积校正（几何）平均浓度增加了一倍。在血清中，顺铂纤维蛋白组的剂量和表面积校正的顺铂暴露（0-5d 时的曲线下面积）明显低于顺铂溶液组（P <.0005）。这也反映在顺铂纤维蛋白组的血清肌酐和尿素值显著降低（P <.0001）。接受顺铂纤维蛋白治疗的动物在术后恢复情况方面也明显更好，表现在舒适度评分方面（P <.001）。
与顺铂溶液治疗相比，顺铂纤维蛋白治疗后，胸壁组织中的顺铂浓度增加，而全身顺铂浓度显著降低。这一发现具有明显的优势，因为可以降低全身不良反应的发生率和严重程度，同时至少维持局部细胞毒性浓度。
