zinostatin and Liver-Cirrhosis

Four patients with advanced hepatocellular carcinoma were treated by repeated arterial infusion of zinostatin stimalamer (SMANCS). Every 4 weeks, 4 mg of SMANCS and 4 ml of Lipiodol were administered via the proper hepatic artery using an implantable arterial port. Three patients with advanced liver cirrhosis (Child B or C) could no longer be treated after 2 or 3 courses of SMANCS infusion because of hepatic failure. In the remaining patient also with compensated liver cirrhosis (Child A), a partial response was observed after 5 courses of chemo-infusion, but we discontinued infusion of SMANCS because of hepatic failure. To assess the usefulness of SMANCS for repeated arterial chemo-infusion by the port, we evaluated 103 patients with advanced HCC treated by Lipiodol emulsion mixed with 70 mg of epirubicin (EPI) using a port. An average course was 11 arterial infusions, and the overall response rate was 40%. One-year survival rates were 62% in Child A, 59% in Child B, and 53% in Child C. Compared with Child A and B patients, both elevation of serum total bilirubin levels and decrease of serum albumin levels were observed after 9 months in Child C patients. In conclusion, SMANCS may have more severe hepatic toxicity in comparison with Lipiodol emulsion mixed with EPI.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Hepatocellular; Drug Administration Schedule; Epirubicin; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Iodized Oil; Liver Cirrhosis; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Polystyrenes; Zinostatin

We report on two patients who developed hepatic infarction after undergoing percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC). In both cases, liver function parameters deteriorated immediately after the ethanol injection, and enhanced computed tomography images showed a wedge-shaped avascular low-density area due to hepatic infarction. In one patient, PEIT was performed for a nodule treated with transcatheter arterial infusion (TAI) using a suspension of styrene maleic acid neocarzinostatin (SMANCS) 4 weeks before. In the other patient, TAI with SMANCS had been carried out 14 months previously for a different nodule in the same segment where the nodule treated with PEIT was located. When PEIT is used for patients with HCC who have previously undergone TAI, especially with SMANCS, PEIT may induce hepatic infarction.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Catheterization, Peripheral; Ethanol; Humans; Infarction; Injections, Intralesional; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Polystyrenes; Tomography, X-Ray Computed; Zinostatin

A 47-year-old man with hepatocellular carcinoma (HCC) at anterior and medical segment in the liver was treated with hepatic arterial infusion of Zinostatin Stimalamer-lipiodol suspension (SMANCS). After the 2nd infusion of SMANCS, the accumulation of lipiodol in the tumor was not good (Grade II), so additional administration was undertaken at five-weeks intervals. His systolic blood pressure immediately decreased from 120 to 60 mmHg, and he had numbness of hands, shaking chills, sweating, chest pain and numerous urticaria-like red exanthema. In spite of treatment by anti-shock agents such as steroid and catecholamines, these symptoms did not disappear, but antihistaminics greatly improved them without any serious side effects. Because of the remarkable effects of the antihistaminics and possibility of antibody production (IgE) after repeated infusions of high molecular SMANCS, this patient may have suffered anaphylactic shock caused by massive histamine release from mast cells.

Topics: Anaphylaxis; Carcinoma, Hepatocellular; Hepatic Artery; Histamine H1 Antagonists; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver Cirrhosis; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Polystyrenes; Zinostatin

For targeted chemotherapy using Lipiodol as a carrier, it was found that anticancer agents had to be dissolved in Lipiodol and diffused gradually from it. Dose forms having properties for targeted chemotherapy were named "oily anticancer agents". Oily anticancer agents are completely different from simple mixture of Lipiodol and anticancer agents by pumping methods in antitumor activities and adverse effects. Up to 1,601 arterial injections of oily anticancer agents were given to 400 patients with unresectable hepatocellular carcinoma. Decrease in serum AFP levels was observed in 209 (94%) of 222 AFP-positive patients, and reduction of tumor size was observed in 308 (96%) of 322 patients who had evaluable tumors. Reduction in size to less than 50% was observed in 50% of patients 5 to 6 months after initial administration, and all tumors reduced to less than 50% one year after. In 45 of 60 patients whose tumors shrank to less than 10% of initial size, follow-up 1 year or more after tumor shrinkage could be done (range 1-9 years, average 3 years). These tumors did not regrow, so they were considered to be cured. Survival was prolonged, especially in 251 patients who were good candidates for therapy (excluding those with Child C liver cirrhosis, tumor occupying all four segments of the liver, and/or extrahepatic spread at initial arterial injection of the drug), the 1-, 2-, and 5-year survival rates were 83, 58, and 34%, respectively.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Hepatocellular; Drug Carriers; Female; Humans; Iodized Oil; Liver Cirrhosis; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Polystyrenes; Zinostatin

I evaluated use of the fluorescence polarization technique to measure neocarzinostatin, a proteinaceous antitumor antibiotic, and its antibody, in serum. The antigen (neocarzinostatin), labeled with fluorescein isothiocyanate, was allowed to interact with its antibody in a cuvet, in the instrument, yielding an increase in the fluorescence polarization value. Antibody content was determined in the presence of a definite amount of the labeled antigen, fluorescence polarization values increasing in parallel with each addition of antibody. Antigen content was determined with a known amount of antibody, which reacted at first with an unknown amount of antigen in samples, followed by addition of a definite amount of the labeled antigen (competition). I used the method to determine a pharmacokinetic parameter, the apparent volume of distribution for neocarzinostatin in rabbits, using drug-injected rabbit sera. I evaluated precision, accuracy, and reproducibility, using various samples or possible interfering substances such as bilirubin and hemoglobin, and also compared results for antigen with those by single radial immunodiffusion assay. The present assay is fast (less than 2 min), sensitive (less than 10 nmol/liter can be detected), and simple (there is no separation step before readout of the results).

Topics: Animals; Antibiotics, Antineoplastic; Antibodies; Bilirubin; Hepatitis; Humans; Hyperlipidemias; Liver Cirrhosis; Rabbits; Radioimmunoassay; Spectrometry, Fluorescence; Zinostatin