zinostatin and Leukopenia

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

Sixty-one of 76 patients entered on a prospective randomized trial of neocarzinostatin ( NCZ ) versus m-AMSA or doxorubicin were eligible for analysis. Among these 61 patients at least one episode of severe toxicity was documented in 39% of patients on NCZ and 58% on m-AMSA. Fifty-one of the 61 patients were previously untreated with chemotherapy. Among these 51 patients objective response was documented in two of 25 patients treated with NCZ , none of 17 treated with m-AMSA, and one of nine treated with doxorubicin. Among previously untreated North American and European (NA/E) patients the median survival times were: NCZ 11 weeks and m-AMSA 12 weeks. The data on South African (SA) patients with similar entrance criteria entered on earlier Eastern Cooperative Oncology Group trials were analyzed with that from the randomized trial and show that for SA patients the median survival times were: NCZ , 11 weeks (31 patients); m-AMSA, 13 weeks (33 patients); and doxorubicin, 15 weeks (29 patients).

Topics: Aminoacridines; Amsacrine; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Clinical Trials as Topic; Doxorubicin; Humans; Leukopenia; Liver Neoplasms; Prospective Studies; Random Allocation; Thrombocytopenia; Zinostatin

Thirty evaluable patients with histologically confirmed primary liver cancer (PLC) were treated with neocarzinostatin (NCS). All patients had measurable disease and an Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, or 3. NCS 2250 units/m2 was given daily for 5 days, repeated at 28-day intervals. Hemopoietic suppression was the major side effect. In 23 of 30 patients (13 with leukopenia and 19 with thrombocytopenia), this toxic effect was documented. Other toxic effects included nausea, vomiting, allergic-type reaction, and elevation of NPN. Partial response, with a median duration of 12.7 weeks (range 4--37 weeks) was observed in seven patients. In nine patients the response was classified as no change, and in 14 patients there was progressive disease. NCS has some therapeutic activity in patients with PLC.

Topics: Adult; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Child, Preschool; Drug Evaluation; Female; Humans; Leukopenia; Liver Neoplasms; Male; Pilot Projects; Thrombocytopenia; Zinostatin

Topics: Adult; Aged; Anorexia; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Fatigue; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Zinostatin

Neocarzinostatin (NCZ), a new antitumor antibiotic, was administered to 19 patients with bladder cancer, 16 patients with prostatic cancer, and 3 patients with hepatoma. All patients had objectively measurable metastatic lesions including 21 with palpable nodes or subcutaneous nodules, 10 with pulmonary nodules as demonstrated by chest x-ray, 4 with malignant hepatomegaly, and 3 with bidimensional pelvic masses as demonstrated by CT scanning. Sixty-five courses of NCZ were administered via an intravenous bolus daily for five days with dosages ranging from 1500 to 3000 U/m2. Immediate toxicity was not dose-limiting except for 1 episode of anaphylaxis and 1 of acute renal failure. Myelotoxicity was delayed, dose-dependent, noncumulative, and dose-limiting. Thrombocytopenia was prolonged or irreversible in 5 cases. The maximally tolerated dose was 2750 U/m2. One patient with NCZ-associated pulmonary fibrosis and 1 with biopsy-proven hepatitis are discussed in detail. Neocarzinostatin demonstrated minimal therapeutic activity (1 partial remission) in patients with bladder cancer. There was no response in patients with prostatic cancer or hepatoma.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Drug Administration Schedule; Drug Evaluation; Female; Hematoma; Humans; Leukopenia; Liver; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Respiratory Function Tests; Thrombocytopenia; Urinary Bladder Neoplasms; Zinostatin