Ichida T, Kato M, Hayakawa A, Ito S, Mori S, Sato T, Sugitani S, Sato H, Watanabe M, Asakura H
Third Department of Internal Medicine, Niigata University School of Medicine, Japan.
Cancer Chemother Pharmacol. 1994;33 Suppl:S74-8. doi: 10.1007/BF00686672.
Prior injection of an anticancer agent and Lipiodol mixture is a key point for the treatment of hepatocellular carcinoma (HCC). We therefore prepared a new, improved emulsion of Lipiodol containing a high dose of cis-diamminedichloroplatinum (CDDP) and epirubicin by replacing the ionic contrast medium (Urografin 67) with a nonionic contrast medium (Iopamidol; Iopamiron 300) and adding phosphatidyl choline. This CDDP-epirubicin-Lipiodol emulsion (CELE) was examined pharmacologically and chemically with the following results. The size of these particles is less than 10 microns (diameter) for up to 24 h; the release of 28%-34% of the CDDP and 80%-90% of the epirubicin was estimated in the dissolution test, and 85% of the CDDP and 35% of the epirubicin was retained in the organs in the moment calculation. CELE was injected into 58 HCC patients via a celiac angiographic catheter. In 36 of these patients, the CELE injection was followed by transcatheter arterial embolization (TAE) therapy. Following the administration of CELE as one-shot injection therapy for stage IV HCC, the 1-year survival rate was 59% and the 2-year survival rate was 27%. Moreover, in patients (stage II, 12; stage III, 8; stage IV, 16) who received CELE and subsequently underwent TAE therapy, the 1-year survival rate was 90% and the 2-year survival rate was 67%. The nonionic contrast medium with Lipiodol forms finer emulsified particles, and these particles are more capable of penetrating into the tumor. In addition, the greater pharmacological stability of these particles provides a slow-release effect and prolonged stability of their shape. Finally, theoretically, the use of two major anticancer agents such as CDDP and epirubicin showed a greater clinical effect in the treatment of HCC than either our earlier suspension or a single anticancer agent.
预先注射抗癌剂与碘油混合物是肝细胞癌（HCC）治疗的关键环节。因此，我们制备了一种新的改良型碘油乳剂，通过用非离子型造影剂（碘帕醇；碘必乐300）替代离子型造影剂（泛影葡胺67）并添加磷脂酰胆碱，使其含有高剂量的顺二氯二氨铂（CDDP）和表柔比星。对这种CDDP - 表柔比星 - 碘油乳剂（CELE）进行了药理和化学检测，结果如下。这些颗粒的大小在长达24小时内小于10微米（直径）；在溶出试验中估计CDDP的释放率为28% - 34%，表柔比星的释放率为80% - 90%，即时计算中85%的CDDP和35%的表柔比星保留在器官中。通过腹腔血管造影导管将CELE注入58例HCC患者体内。其中36例患者在注入CELE后接受了经导管动脉栓塞（TAE）治疗。将CELE作为IV期HCC的一次性注射治疗给药后，1年生存率为59%，2年生存率为27%。此外，在接受CELE并随后接受TAE治疗的患者（II期12例；III期8例；IV期16例）中，1年生存率为90%，2年生存率为67%。含碘油的非离子型造影剂形成更细小的乳化颗粒，这些颗粒更能渗透到肿瘤中。此外，这些颗粒更强的药理稳定性提供了缓释效果并延长了其形状的稳定性。最后，从理论上讲，使用CDDP和表柔比星这两种主要抗癌剂在HCC治疗中比我们早期的混悬液或单一抗癌剂显示出更大的临床效果。
