Wang H Y, Hochwald S, Ng B, Burt M
Thoracic Oncology Laboratory, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Anticancer Res. 1996 Nov-Dec;16(6B):3749-53.
This study is to evaluate low dose doxorubicin pulmonary artery perfusion with blood flow occlusion compared to systemic administration in a model of solitary intrapulmonary sarcoma nodule in the rat. Tumor nodule was developed via injection of methylcholanthrene-induced sarcoma into the left lung. Doxorubicin was perfused into the left pulmonary artery at a rate of 50 microliters/min for 2 min with 20 min blood flow blockage in all experiments. Pharmacokinetics, toxicity, treatment efficacy were compared between lung perfusion groups and intravenous groups. Doxorubicin levels in tumor, left lung, right lung, heart and serum were measured. Animal daily weights were recorded and a right pneumonectomy was performed following treatment to assess toxicity and tolerated perfusion dose. Tumors were weighed following treatment to evaluate treatment efficacy. Doxorubicin delivered via pulmonary artery caused a significant higher drug level in tumor tissue and perfused lung with a low drug level in heart, right lung and serum as compared to intravenous administration. Animals in perfusion groups had normal growth pattern and survived after pneumonectomy when a dose of 0.5 mg/kg doxorubicin was perfused. Tumor weight was significantly decreased after treated with 0.5 mg/kg of doxorubicin lung perfusion as compared to same dose of doxorubicin intravenous treatment. Pulmonary artery perfusion with blood flow occlusion may offer an effective lung chemotherapeutic model. 0.5 mg/kg doxorubicin for lung perfusion has acceptable local lung toxicity and no significant systemic toxicity and is pharmacokinetically and therapeutically superior to systemic administration in this solitary intrapulmonary tumor nodule model in the rat.
本研究旨在评估在大鼠孤立性肺内肉瘤结节模型中，与全身给药相比，低剂量阿霉素肺动脉灌注加血流阻断的效果。通过将甲基胆蒽诱导的肉瘤注射到左肺来形成肿瘤结节。在所有实验中，阿霉素以50微升/分钟的速率灌注到左肺动脉中，持续2分钟，并进行20分钟的血流阻断。比较肺灌注组和静脉注射组的药代动力学、毒性和治疗效果。测量肿瘤、左肺、右肺、心脏和血清中的阿霉素水平。记录动物每日体重，并在治疗后进行右肺切除术以评估毒性和耐受的灌注剂量。治疗后称量肿瘤重量以评估治疗效果。与静脉给药相比，通过肺动脉给药导致肿瘤组织和灌注肺中的药物水平显著更高，而心脏、右肺和血清中的药物水平较低。当灌注0.5毫克/千克阿霉素时，灌注组动物具有正常的生长模式，并且在肺切除术后存活。与相同剂量的阿霉素静脉治疗相比，0.5毫克/千克阿霉素肺灌注治疗后肿瘤重量显著降低。肺动脉灌注加血流阻断可能提供一种有效的肺化疗模型。在大鼠的这个孤立性肺内肿瘤结节模型中，0.5毫克/千克阿霉素用于肺灌注具有可接受的局部肺毒性，无明显全身毒性，并且在药代动力学和治疗方面优于全身给药。
