Phase I study with neocarzinostatin: tolerance to two hour infusion and continuous infusion.
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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001853:Bone Marrow / Q000187:drug effects; D002648:Child; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004361:Drug Tolerance; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007263:Infusions, Parenteral; D007938:Leukemia / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D012075:Remission, Spontaneous; D014511:Uremia / Q000139:chemically induced; D009353:Zinostatin / Q000008:administration & dosage* / Q000633:toxicity
D000903:Antibiotics, Antineoplastic; D009353:Zinostatin