Chemotherapy and Inhibition for Metastatic Live Cancer of Liposome-Entrapped Adriamycin Experimetal and Clinical Studies of Portal Vein Administration

我们研究了冻干脂质体包载阿霉素（Lipo-ADM）经门静脉给药对兔VX 2肿瘤的组织分布和抗肿瘤作用。以卵磷脂（胆固醇50mol%）组成的脂质体作为药物载体。与游离药物治疗相比，阿霉素给药后肝脏浓度增加，心脏摄取减少。采用兔VX 2肿瘤模型，观察Lipo-ADM的体内抗肿瘤作用。经门静脉重复注射，可延长荷瘤兔的寿命。Lipo-ADM治疗组与对照组和游离ADM组相比，上述时间进一步延长。组织学检查显示，经门静脉给予Lipo-ADM引起的损伤与用游离ADM治疗的动物中观察到的损伤没有差异。这些结果表明，门静脉给予Lipo-ADM可能比游离ADM治疗更有效地处理肝转移，并且可能 ...更多信息 在治疗上是有用的而没有毒副作用。考虑到这些结果，我们研究了经门静脉给药的Lipo-ADM的效果以及这种治疗在治疗和抑制肝转移中的临床应用。在临床评价中，使用皮下植入的储药器通过门静脉进行化疗。10例患者经门静脉给予Lipo-ADM（20-30 mg/2周）治疗并评价临床疗效。门静脉给药未见肝功能损害、骨狭窄抑制等不良反应。9例既往接受游离ADM和MTX-5 FU治疗的患者术后平均生存时间为141天。而Lipo-ADM治疗组10例，平均生存期为439 d，其中3例胃癌和1例子宫癌术后生存468 d，2例生存600 d以上。这项研究表明，使用Lipo-ADM经门静脉化疗不能手术的转移性肝癌显着提高生存时间。少

We examined the tissue distributions and antitumor effect of freeze-dried liposome-entrapped adriamycin (Lipo-ADM) administered via the portal vein to rabbits bearing VX2 tumors. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. Liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The in vivo antitumor effect of Lipo-ADM was determined in rabbits inoculated VX2 tumor. Repeated injections via the portal vein, prolonged the life-spans of tumor-bearing rabbits. Lipo-ADM treatment further prolonged those compared with the control group and the free ADM group. Histological examination revealed that the damage caused by Lipo-ADM administered via the portal vein did not differ from that observed in animals treated with free ADM. These results indicate that portal vein administration of Lipo-ADM may be more effective in dealing with liver metastases than treatment with free ADM and may … More be therapeutically useful without toxic side effects. Considering these results we have studied the effect of Lipo-ADM administered via the portal vein and the clinical application of this treatment in the therapy and inhibition of the liver metastases. In clinical evaluations, chemotherapy via the portal vein was performed using a subcutaneously implanted reservoir. 10 patients were treated via the portal vein with Lipo-ADM (20-30 mg/2 weeks) and the clinical effects evaluated. No liver dysfunction, bone narrow suppression or other side effects were noted when Lipo-ADM was administered via the portal vein. The postoperative mean survival time was 141 days for 9 patients treated previously with free ADM and MTX-5FU therapy. In contrast, the mean survival time was 439 days for 10 patients treated with Lipo-ADM therapy ; moreover, 3 cases of gastric cancer and one case of uterine cancer survived for 468 days postoperatively, and 2 cases have survived for more 600 days. This study demonstrates that chemotherapy using Lipo-ADM via the portal vein in inoperable metastatic liver cancer markedly improves the survival time. Less