Phase I study with neocarzinostatin. Tolerance to two hour infusion and continuous infusion

Abstract

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 × 5 days. One patient with previously treated acute myelocytic leukemia was induced into a good partial remission lasting 10 weeks. Cancer 42:1670–1679, 1978. Copyright © 1978 American Cancer Society