[Targeting cancer chemotherapy using lipiodol as a carrier of anticancer drugs for hepatocellular carcinoma].
We have found that the lipid lymphographic agent, Lipiodol ultrafluid, remains selectively in hepatocellular carcinoma and other malignant solid tumors. Lipiodol administered arterially flows into the normal blood vessels of normal tissues and into the neovasculature of the tumor. Selective retention of Lipiodol in the tumor occurs due to early removal from the normal blood vessels and retention in the neovasculature and extravascular space in the tumor. Using this characteristic nature of Lipiodol, targeting cancer chemotherapy was achieved. It was shown that anticancer drugs had to be dissolved in Lipiodol and diffuse out gradually from the agent in order to achieve targeting cancer chemotherapy. Various kinds of oily anticancer agents which facilitate targeting cancer chemotherapy, such as SMANCS/Lipiodol, mitomycin/Lipiodol, adriamycin/Lipiodol and aclarubicin/Lipiodol were successfully developed. Clinically, these oily anticancer agents were administered to 260 patients with hepatocellular carcinoma. Selective long-lasting retention of Lipiodol in hepatocellular carcinoma was proved on the basis of CT and low-kVp X-ray examination, and persistent high biological activities of anticancer drugs in the tumor were also recognized. The serum AFP level and tumor size showed a decrease in 92% and 90% of cases, respectively. The survival period of these patients with unresectable tumor treated with this protocol was definitely longer than in the comparison group, i.e., the 50% survival period for the comparison group was 1.3 months, while that of the patients who received this protocol was 13 months. In patients administered a SMANCS dose of more than 0.25mg/cm2 of maximum cut-surface area, complete necrosis of the tumor was found, and importantly, non-cancerous liver tissue remained unaffected. Neither hematosuppression nor any severe side effects due to anticancer drugs were observed. Remarkable antitumor effects and reduced side effects could thus be achieved by targeting chemotherapy using Lipiodol as a carrier of anticancer drugs.
Konno
T
T
1st Dept. of Surgery, Kumamoto University Medical School.
Maeda
H
H
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004337:Drug Carriers; D006801:Humans; D007269:Injections, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008299:Maleic Anhydrides / Q000008:administration & dosage; D011137:Polystyrenes / Q000008:administration & dosage; D009353:Zinostatin / Q000008:administration & dosage / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D007459:Iodized Oil; D009353:Zinostatin