zinostatin and Remission--Spontaneous

Topics: Altretamine; Ancitabine; Antimetabolites, Antineoplastic; Antineoplastic Agents; Azacitidine; Cisplatin; Clinical Trials as Topic; Dacarbazine; Doxorubicin; Drug Evaluation; Drug Therapy, Combination; Etoposide; Humans; Mitolactol; Nitrosourea Compounds; Razoxane; Remission, Spontaneous; Tamoxifen; Time Factors; Vinca Alkaloids; Zinostatin

Neocarzinostatin (NCZ), an acidic polypeptide antibiotic, was given to 47 patients with cancer and leukemia, and tolerance to two schedules, a single dose given as a 2 hour infusion and a continuous infusion over 5 days was investigated. Immediate reactions, including fever, chills, rigor, hypertension and mental confusion, were dose-limiting for the 2 hour infusion schedule, occurring at 3000 U/m2 and higher. Continuous administration for 5 days eliminated the immediate reactions and then hematological toxicity--often prolonged leukopenia and thrombocytopenia--became dose-limiting. Other toxicities of NCZ at both dose schedules included anemia, fever and chills, anorexia, nausea and vomiting, hepatic dysfunction, azotemia, hypophosphatemia, aminoaciduria, stomatitis, phlebitis and/or cellulitis at the venous infusion site and pruritus. Patients with solid tumors who had received little or no prior chemotherapy and had good bone marrow reserve tolerated up to 6000 U/m2/24 hours X 5 days. One patient with previously treated acute myelocytic leukemia was induced into a good partial remission lasting 10 weeks.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Bone Marrow; Child; Drug Administration Schedule; Drug Evaluation; Drug Tolerance; Female; Fever; Humans; Hyperbilirubinemia; Infusions, Parenteral; Leukemia; Leukemia, Myeloid, Acute; Male; Middle Aged; Neoplasms; Remission, Spontaneous; Uremia; Zinostatin

Twenty-three children with advanced cancer refractory to conventional therapy received weekly iv doses of neocarzinostatin for 5 weeks. Doses were escalated from 500 to 6750 units/m2/week. Four types of toxic manifestations occurred: acute reactions consisting of shaking chills with or without fever and cyanosis (rigor), hypersensitivity, vomiting, and marrow depression. Evidence of oncolytic activity was limited to patients with acute leukemia in whom phase II trials at doses between 3000 and 4500 units/m2 appear warranted.

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Bone Marrow; Child; Child, Preschool; Drug Evaluation; Drug Hypersensitivity; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Neoplasms; Remission, Spontaneous; Shivering; Vomiting; Zinostatin

Neocarzinostatin is a protein antitumor antibiotic isolated from cultures of Streptomyces carzinostaticus var.F41. The drug has undergone extensive clinical trial in Japan, and has been reported active against a variety of human tumors. A phase I and preliminary phase II evaluation of the drug has been performed, using an iv bolus daily x 5 schedule. Ninety-six patients have been treated at doses from 500 to 2250 units/m2/day. Courses were repeated at 4-week intervals if allowed by bone marrow recovery. Dose-limiting toxicity was myelosupppression, which occurred late (median nadir, Day 27). Myelosuppression was more pronounced in patients who had received previous chemotherapy. In nine patients (9%) thrombocytopenia was prolonged (greater than or equal to 45 days) or irreversible. Acute administration of the drug was associated with rigors in approximately half the patients. Gastrointestinal side effects were mild. Three patients had a severe acute reaction resembling anaphylaxis. The maximally tolerated dose for this dose schedule is approximately 2250 units/m2/day. Antitumor activity has been seen in hepatoma and hematologic malignancies. Activity in lung and colorectal carcinoma appears limited with this dose schedule.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Bone Marrow; Carcinoma, Hepatocellular; Child; Drug Evaluation; Female; Humans; Leukemia, Lymphoid; Liver Neoplasms; Male; Middle Aged; Neoplasms; Remission, Spontaneous; Thrombocytopenia; Zinostatin

Topics: Acute Disease; Adult; Antineoplastic Agents; Azacitidine; Blood Transfusion; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Granulocytes; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Patient Isolation; Platelet Transfusion; Pneumonia; Prednisone; Pyrimethamine; Remission, Spontaneous; Thioguanine; Vincristine; Zinostatin

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Remission, Spontaneous; Zinostatin

Topics: Acute Disease; Antibiotics, Antineoplastic; Drug Evaluation; Humans; Leukemia; Middle Aged; Remission, Spontaneous; Zinostatin