Phase I study of 2'-deoxycoformycin in acute lymphoblastic leukemia.
2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzyme elevations, and conjunctivitis. Lymphopenia occurred in all patients. The most serious adverse effects were acute tubular necrosis and central nervous system toxicity, which appeared to be dose related. In addition, two patients given the 0.75-mg/kg dose developed severe hepatic toxicity, although this could not be ascribed definitively to 2'-dCF. Antitumor activity was observed in eight patients, two of whom experienced a complete remission. Inhibition of lymphoblast adenosine deaminase activity was noted in the majority of cases and was observed at all doses. Antileukemic activity occurred at doses of 2'-dCF which were not associated with limiting toxicities. These results suggest that 2'-dCF is active against acute lymphoblastic leukemia and that a starting dose of 0.5 mg/kg/day be utilized in Phase II studies.
D058892:Adenosine Deaminase Inhibitors; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003070:Coformycin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D009325:Nausea / Q000139:chemically induced; D015649:Pentostatin; D011379:Prognosis; D012263:Ribonucleosides / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced
D058892:Adenosine Deaminase Inhibitors; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin