Phase I clinical study with 5'-deoxy-5-fluorouridine, a new fluoropyrimidine derivative.
5'-Deoxy-5-fluorouridine (DFUR) is a new fluoropyrimidine derivative with significant antineoplastic activity in animal systems. Compared to 5-FU or other fluoropyrimidines, DFUR has a more favorable therapeutic ratio in Sarcoma 180-bearing mice. DFUR was studied in this phase I trial with a daily x 5 bolus iv injection. A second course was given greater than or equal to 3 weeks after the first day of treatment. Doses were escalated from 300 to 5000 mg/m2/day in 30 patients. Dose-limiting factors were myelosuppression and stomatitis. Hematologic toxic effects were particularly marked on granulocytes. Thrombocytopenia was less frequently encountered. Stomatitis was severe at high doses of DFUR. Eleven patients had nausea or moderate vomiting. Drug-induced myocardial injury may exist, since electrocardiogram changes were recorded in two patients. After rapid iv injection, four patients felt hot in the face and pelvis. Other side effects were minimal. With this daily x 5 schedule of administration, the maximum tolerated dose of DFUR appeared to be 5000 mg/m2/day. The dose recommended for further clinical use is 4000 mg/m2/day x 5 for patients previously untreated with chemotherapy.
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010976:Platelet Count; D013280:Stomatitis / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D005467:Floxuridine; C025034:doxifluridine