Phase I trial of chlorozotocin: attempted amelioration of myelotoxicity by glucose administration.
Chlorozotocin is a new anticancer agent with the chloroethylnitrosourea cytotoxic moiety attached to the carbon-2 position of glucose. Like other chloroethylnitrosoureas, this agent produces delayed myelotoxicity which is dose-limiting. A phase I trial of chlorozotocin with administration of glucose was done in an attempt to modify the myelotoxicity. The patients received the first course of chlorozotocin (200 mg/m2) in the fasting state and then the second course of chlorozotocin with boluses of a 50% glucose solution. With the second course of chlorozotocin administration, the glucose concentration remained threefold greater than after the first course for at least 1 hour. The plasma half-life and apparent volume of distribution of chlorozotocin were similar following either course. The wbc, neutrophil, and platelet count nadirs after the first course of this agent were not significantly different than the nadirs after the second course. We were unable to modify the myelotoxicity of chlorozotocin with boluses of a 50% glucose solution.
D001786:Blood Glucose; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000517:prevention & control; D004341:Drug Evaluation; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D009196:Myeloproliferative Disorders / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy; D011379:Prognosis; D013311:Streptozocin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood
D001786:Blood Glucose; C007028:chlorozotocin; D013311:Streptozocin; D005947:Glucose