Swistel A J, Bading J R, Raaf J H
Cancer. 1984 Mar 15;53(6):1397-404. doi: 10.1002/1097-0142(19840315)53:6<1397::aid-cncr2820530630>3.0.co;2-e.
Intraarterial (IA) chemotherapy can theoretically result in a high tissue level of the drug with reduced systemic toxicity compared with intravenous (IV) administration. The authors compared these two modes of therapy using Adriamycin (doxorubicin) in the rabbit Vx-2 tumor system. Vx-2 was implanted in hind limb muscle, and silastic catheters were placed in the jugular vein and femoral artery. Nuclear imaging of technetium-99m-labeled autologous erythrocytes in nine animals was used to measure the kinetics of tumor blood flow. Presence of tumor increased flow through the involved limb up to threefold. One minute following injection there was no difference in concentration of 99mTc in tumor whether labeled cells were introduced IA or IV. Twelve rabbits received IA (N = 6) or IV (N = 6) Adriamycin (3 mg/kg), while eight animals received normal saline IA or IV as controls. Tumor progressed in all control rabbits, whereas there was an objective or complete response in 83% of animals receiving Adriamycin. One hundred percent of those treated IA responded compared with 67% for IV (P = 0.04). Median time to initial response in animals treated IA was 7 days versus 21 days for those treated IV (P = 0.02). Thus, IA Adriamycin achieves a more complete and more rapid response than the drug given IV. This occurs despite a large tumor blood flow and rapid equilibration using both methods.
动脉内(IA)化疗理论上可使药物在组织中达到较高水平,与静脉内(IV)给药相比,全身毒性降低。作者在兔VX-2肿瘤系统中比较了使用阿霉素(多柔比星)的这两种治疗方式。将VX-2植入后肢肌肉,并将硅橡胶导管置于颈静脉和股动脉中。对9只动物进行99m锝标记的自体红细胞核成像,以测量肿瘤血流动力学。肿瘤的存在使受累肢体的血流量增加了两倍。注射后1分钟,无论标记细胞是经动脉内还是静脉内注入,肿瘤中99mTc的浓度均无差异。12只兔子接受动脉内(N = 6)或静脉内(N = 6)阿霉素(3mg/kg)治疗,而8只动物接受动脉内或静脉内生理盐水作为对照。所有对照兔的肿瘤均进展,而接受阿霉素治疗的动物中有83%出现客观反应或完全缓解。接受动脉内治疗的动物中有100%有反应,而静脉内治疗的动物为67%(P = 0.04)。接受动脉内治疗的动物初始反应的中位时间为7天,而接受静脉内治疗的动物为21天(P = 0.02)。因此,动脉内给予阿霉素比静脉内给药能实现更完全、更快速的反应。尽管两种方法的肿瘤血流量都很大且平衡迅速,但仍会出现这种情况。