Phase I evaluation of 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine in immunosuppressed patients with herpesvirus infection.
2'-Fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine (FIAC) is a potent selective inhibitor of the replication of herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella zoster virus, and cytomegalovirus in cell culture systems. FIAC produces an unequivocal therapeutic effect in mice that have been inoculated with a lethal burden of HSV-1. We have administered FIAC to 32 host compromised patients, 30 with advanced cancer, who were experiencing acute herpesvirus infections (varicella zoster, 29; HSV-1, 2; HSV-2, 1); the drug was given by 20 min i.v. infusion twice a day for 7 days. The dosage levels explored were 60, 120, 240, 400, and 600 mg/sq m/day. Drug-induced myelosuppression became evident at 600 mg/sq m/day; thrombocytopenia exceeded leukopenia. The toxic low dose was 400 mg/sq m/day with mild nausea and rare myelosuppression. All 24 varicella zoster patients with cutaneous disease receiving FIAC, greater than or equal to 120 mg/sq m/day, experienced stabilization of cutaneous lesions within 48 to 72 hr; healing began promptly thereafter.
D000998:Antiviral Agents; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004341:Drug Evaluation; D006410:Hematopoiesis / Q000187:drug effects; D006566:Herpesviridae Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007165:Immunosuppression Therapy; D009369:Neoplasms / Q000150:complications
D000998:Antiviral Agents; D003561:Cytarabine; C026023:fiacitabine