zinostatin and Nausea

Neocarzinostatin is a new anticancer drug developed by Japanese investigators. In order to delineate the potential usefulness of this drug, we have reviewed the preclinical data and summarized the Japanese clinical data on 462 patients. The bulk of these patients had carcinoma of the stomach or pancreas and acute leukemia. Neocarzinostatin was administered intravenously in a daily dose of 2-3 mg for five to 15 day periods. Significant antitumor activity was observed in acute leukemia. A few responses were also reported in pancreatic adenocarcinoma, but the drug was inactive against gastric carcinoma. The side effects observed included nausea, vomiting, myelosuppression, fever, and occasional hypersensitivity reactions. The Investigational Drug Branch of the National Cancer Institute has recently sponsored an investigational new drug application with the Food and Drug Administration, and phase I studies are expected to begin soon in the United States.

Topics: Amino Acids; Animals; Antibiotics, Antineoplastic; Cell Division; Chemical Phenomena; Chemistry; Diarrhea; DNA Replication; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Eruptions; Fever; Humans; Hypotension; Kidney Diseases; Leukopenia; Molecular Weight; Nausea; Neoplasms; Neoplasms, Experimental; Temperature; Templates, Genetic; Thrombocytopenia; Zinostatin

A phase II study of YM 881 (zinostatin stimalamer) to determine the response and safety was conducted in patients with hepatocellular carcinoma by injecting a suspension of the drug into the hepatic artery. Repeated doses of 4 to 6 mg of the drug were given every 4 weeks so that the tumor tissues were filled with the suspension. Of the 195 registered patients, 15 were ineligible for the study, 8 dropped out, and data were missing for 5. A total of 167 patients completed the study. Response was assessed in the 167 patients who completed the study. CR was found in one, PR in 59, MR in 25, NC in 67, and PD in 15, with a response rate of 35.9. The safety of the drug was assessed in 177, excluding ineligible patients and 3 who dropped out because of the concurrent use of other drugs. Adverse reactions were found in 93.2% of the patients, and abnormal values in clinical laboratory tests in 60.5%. Major unwanted symptoms included fever, nausea, vomiting, and anorexia. Major abnormal changes in laboratory tests were elevated total bilirubin and LDH and abnormal hepatic function. About half the patients had malaise and pain related to the intra-arterial infusion therapy. The one year survival rate was 56.9%, and the duration of survival of 50% of the patients was 407 days.

Topics: Adult; Aged; alpha-Fetoproteins; Anorexia; Carcinoma, Hepatocellular; Drug Administration Schedule; Drug Evaluation; Female; Fever; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Nausea; Polystyrenes; Survival Rate; Zinostatin

To determine the incidence of nausea and vomiting and the antiemetic effect of ondansetron hydrochloride (OND) in patients with hepatocellular carcinoma treated with arterial chemo-embolization, we studied 59 patients with hepatocellular carcinoma who were treated with transcatheter arterial embolization (TAE) or lipiodolized transcatheter arterial infusion (L-TAI). We investigated the incidence of nausea and vomiting and the amount of food intake when TAE or L-TAI was performed. All patients who experienced nausea and vomiting received OND administered prophylactically at the time of the next TAE or L-TAI to evaluate the antiemetic effect of the drug. Cumulative rates of nausea and vomiting during the week following arterial chemo-embolization were 44.8% and 27.6%, respectively. There was a tendency for the incidence to be higher in patients treated with the anticancer agent zinostatin stimalamer (SMANCS) than in those treated with epirubicin hydrochloride (EPI). Regarding food intake, 53.1% of the patients stated that they ate "half or more than half" of the food provided on the day of arterial chemo-embolization. The rate improved as time went on. In 5 patients who experienced nausea and vomiting at the time of arterial chemo-embolization, nausea and vomiting were inhibited satisfactorily by OND. When arterial chemo-embolization was performed, antiemetic treatment for approximately 3 days was necessary to improve patients' quality of life (QOL) to an acceptable level, and OND was found to be effective for the purpose in our 5 patients who had experienced nausea and/or vomiting at the previous treatment.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antiemetics; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Eating; Epirubicin; Female; Follow-Up Studies; Humans; Incidence; Infusions, Intra-Arterial; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Mitomycin; Nausea; Ondansetron; Polystyrenes; Quality of Life; Vomiting; Zinostatin

Though SMANCS-Lipiodol suspension has advantages over tumor regression, its disadvantages should also be considered: (1) Anaphylactic reaction due to its high molecular weight. (2) Since it readily destroys the tissue, a smaller dose and repeated administration are required. (3) Due to its low viscosity, it easily enters the arterioles and causes damage even to the extrahepatic organs. When this drug is infused into the left hepatic artery in subsegmental fashion, it enters the neighboring gastric tissues through the communication of the left hepatic and left gastric arteries, and this ultimately causes intractable gastric ulcers. Considering the above facts, this drug should be used carefully.

Topics: Adult; Aged; Anaphylaxis; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Drug Administration Schedule; Female; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Nausea; Polystyrenes; Stomach Ulcer; Vomiting; Zinostatin

We investigated the possible side effects and efficacy of arterial infusion of SMANCS as compared to Lipiodol + epirubicin TAE for multiple recurrent tumors after hepatic resection. As a result, no significant difference in GOT, GPT, and total bilirubin was observed between the two groups. No significant difference was found in white blood cell count and platelet count, and there was no significant difference in clinical side effects between the two groups. Grade III response rates after arterial infusion of SMANCS were found in 4 patients (66.6%), and these results showed no significant difference as compared to Lipiodol + epirubicin TAE. Proper hepatic arterial infusion of SMANCS appeared to be useful in multiple recurrent tumors from the standpoints of safety and the rate of Lipiodol deposition.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Hepatocellular; Embolization, Therapeutic; Epirubicin; Female; Hepatectomy; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Nausea; Neoplasm Recurrence, Local; Polystyrenes; Zinostatin

A phase I study of YM-881 (zinostatin stimalamer), neocarzinostatin combined with butylesterified styrene maleate, suspended in iodized poppy oil ethyl ester, was conducted in patients with hepatocellular carcinoma by giving single intra-arterial infusions via catheters inserted by Seldinger's method. Four dose levels, 2, 4, 6, and 8 mg, were tested. Major adverse reactions were fever, anorexia, nausea, vomiting, and abnormal hepatic function. Both the incidence and severity of adverse reactions tended to increase with the 8 mg dose. Tumor regression of 50% or more occurred in one receiving 2 mg and one receiving 4 mg. The results of the study suggest that doses of 6 mg or less may be appropriate for the phase II studies.

Topics: Adult; Aged; Anorexia; Carcinoma, Hepatocellular; Drug Administration Schedule; Drug Evaluation; Female; Fever; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Nausea; Polystyrenes; Zinostatin