Smancs

We have developed the prototype macromolecular anticancer agent SMANCS (Figure 7) at first 197 9 3 4 48-51 as an active principle. SMANCS is more commonly used with LipiodolĀ®, a carrier vehicle, given by arterial injection using catheter via the tumor-feeding arteries 50-51. Lipiodol is an iodinated ethylester of poppyseed oil manufactured by Laboratoire Guerbet in France; it can be administered intraarterially upstream from the tumorfeeding artery, i.e., the hepatic artery for hepatoma, and the bronchial artery for lung cancer for example. In an experimental model of metastatic hepatoma in rabbits, the ratio of the drug (lipid) concentration in the tumor (T) to that in blood plasma (B) (T/B) is more than 2000 27, 29. Furthermore, the drug remains at high concentration without being cleared from the tumor matrix for up to several weeks, because of its slow clearance as a result of EPR effect3-6, 8 14-16, 26, 49-57; this pronounced retention of lipid contrast agent (Lipiodol) given arterially achieve most remarkable EPR effect, partly by first-pass capture and it is of course much effective than proteins.

Figure 7. Chemical structure of SMANCS,

Treatment of primary hepatoma by the SMANCS/Lipiodol method has been approved in Japan for more than 6 years, since 1995. When the drug is delivered by intraarterial administration using catheter, this treatment produces definite tumor size reduction (in >90% of cases), improved survival scores, and especially a good quality of life with very little side effect (Table 4)58. Furthermore, patients can be out of bed within a few days after the procedure (the Seldinger method is used for arterial infusion under the X-ray system). For all cases of primary hepatoma combined (including Child's criteria of A-C cirrhosis), the 5- to 7- year survival rate is about 30% with this method. With other treatments, no survival would be expected during this time frame. Hepatoma patients with milder liver cirrhosis (such

Table 4. Side effects of intraaterial SMANCS/LPD therapy in hepatoma patients J>

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