[Liver tumor targeting of drugs: Spherex, a vascular occlusive agent].
Embolizing chemotherapeutic methods are presently used primarily for nonresectable metastatic hepatic carcinoma. Because this kind of carcinoma is generally ischemic, little is expected from embolizing chemotherapeutic methods aimed at tumor necrosis by blood flow obstruction using gelatin sponges. On the other hand, since the arrival rate of Lipiodol is not very good, embolizing chemotherapeutic therapy employing Lipiodol is not expected to be very effective. Consequently, therapies against metastatic hepatic carcinoma have mainly been intraarterial chemotherapies without embolization. Spherex is a transient embolization agent prepared by suspending 60 mg/ml of degradable starch microspheres (hereinafter, DSM) in physiological saline. It was developed by Pharmacia AB, Sweden, as an arterial embolizing agent for embolizing chemotherapy, and it was the first agent approved for use in Japan as an embolization material. DSM is composed of spherical particles approx. 45 microns in diameter prepared by crosslinking partially hydrolyzed potato starch using epichlorohydrin as a crosslinking agent, and it is characterized by gradual decomposition by blood amylase, having a half-life of 20-35 minutes in vitro. Clinically, when Spherex is administered via the arteries, embolization has been found to occur in the arterioles. Furthermore, administration of Spherex via the hepatic artery in combination with an anticancer drug results in the formation of transient reduction of bloodflow, thus making it possible to extend the period of retention of the anticancer drug at a high concentration in the tumorous region. As a result, the local antitumor effect of the anticancer drug may be reinforced, with alleviation of systemic side effects. In clinical tests involving its administration to metastatic hepatic tumors in combination with mitomycin C (hereinafter, MMC), the efficacy is 54.5% with arterial injection therapy with Spherex, which is significantly superior to the 20.0% obtained with arterial injection of MMC alone. Although the rate of side effects exhibited, including pain, digestive symptoms and fever, has been significantly higher in combination with Spherex, myelosuppression indicated by abnormal fluctuations in leukocyte and platelet counts was found to be greater with administration of MMC alone, suggesting its value as an effective future therapy for metastatic hepatic carcinoma. These data indicate that Spherex is not expected to yield an antitumor effect due to long-term blood flow obstruction in the hepatic artery, an effect associated with gelatin sponges heretofore used for embolizing chemotherapy. Instead, it causes a transient occlusion upon one-shot intraarterial injection therapy with MMC, thus extending the retention time of MMC at high concentration in tumorous sections, thereby yielding a high local antitumor effect with MMC.(ABSTRACT TRUNCATED AT 400 WORDS)
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Osaka University.
D016461:Chemoembolization, Therapeutic; D004317:Doxorubicin / Q000008:administration & dosage; D006499:Hepatic Artery; D006801:Humans; D007269:Injections, Intra-Arterial; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008863:Microspheres; D016685:Mitomycin / Q000008:administration & dosage; D013213:Starch / Q000008:administration & dosage*
D016685:Mitomycin; D004317:Doxorubicin; C044817:Spherex; D013213:Starch