Nawata S, Abecasis N, Ross H M, Abolhoda A, Cheng H, Sachar K S, Burt M E
Thoracic Oncology Laboratory/Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021, USA.
J Thorac Cardiovasc Surg. 1996 Dec;112(6):1542-7; discussion 1547-8. doi: 10.1016/S0022-5223(96)70013-2.
Isolated lung perfusion allows the delivery of high-dose chemotherapy to the perfused lung and is an efficacious modality in the treatment of pulmonary metastases in the rat. Melphalan activity in this model was investigated.
TOXICITY STUDY: Maximum tolerated dose of melphalan delivered by means of isolated lung perfusion was determined by survival after contralateral pneumonectomy. PHARMACOKINETICS STUDY: Nineteen rats were treated with melphalan administered either by isolated lung perfusion (2 mg) or intravenously (2 mg or 1 mg). Lung, pulmonary effluent, and serum melphalan were analyzed by high-pressure liquid chromatography. EFFICACY STUDY: On day 0, 41 rats received an intravenous injection of 5 x 10(6) methylcholanthrene induced sarcoma cells. On day 7, rats either received intravenous melphalan (2 mg [n = 10]; 1 mg [n = 8]) or underwent left isolated lung perfusion with 2 mg of melphalan (n = 12). Isolated lung perfusion with buffered hetastarch in sodium chloride (Hespan, n = 11) was used as control. On day 14, pulmonary nodules were counted.
Maximum tolerated dose of melphalan delivered buy means of isolated lung perfusion was 2 mg.
Left lung melphalan level was significantly higher in the isolated lung perfusion group (62.2 +/- 34.3 microg/gm lung) than in the intravenous treatment groups (6.9 +/- 1.9 microg/gm lung and 3.3 +/- 0.9 microg/gm lung, respectively) (p = 0.0002).
Significantly fewer left lung nodules were found in animals receiving melphalan by means of isolated lung perfusion (7 +/- 10) than in the groups receiving intravenous melphalan (60 +/- 21) or buffered hetastarch by isolated lung perfusion (84 +/- 52) (p = 0.01 and p = 0.0001, respectively).
Isolated lung perfusion with melphalan is safe and effective in the treatment of pulmonary sarcoma metastases in the rat.
孤立肺灌注可将高剂量化疗药物输送至灌注肺，是治疗大鼠肺转移瘤的一种有效方式。本研究对美法仑在该模型中的活性进行了探究。
毒性研究：通过对侧肺切除术后的存活率来确定经孤立肺灌注给予美法仑的最大耐受剂量。药代动力学研究：19只大鼠接受美法仑治疗，给药方式为孤立肺灌注（2mg）或静脉注射（2mg或1mg）。采用高压液相色谱法分析肺组织、肺流出液及血清中的美法仑。疗效研究：第0天，41只大鼠静脉注射5×10⁶甲基胆蒽诱导的肉瘤细胞。第7天，大鼠要么接受静脉注射美法仑（2mg[n = 10]；1mg[n = 8]），要么用2mg美法仑进行左肺孤立灌注（n = 12）。用氯化钠缓冲羟乙基淀粉（贺斯，n = 11）进行孤立肺灌注作为对照。第14天，计数肺结节。
经孤立肺灌注给予美法仑的最大耐受剂量为2mg。
孤立肺灌注组左肺美法仑水平（62.2±34.3μg/g肺）显著高于静脉治疗组（分别为6.9±1.9μg/g肺和3.3±0.9μg/g肺）（p = 0.0002）。
经孤立肺灌注接受美法仑治疗的动物左肺结节数（7±10）显著少于接受静脉注射美法仑的组（60±21）或经孤立肺灌注接受缓冲羟乙基淀粉的组（84±52）（分别为p = 0.01和p = 0.0001）。
美法仑孤立肺灌注治疗大鼠肺肉瘤转移安全有效。
