Phase I evaluation of 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine in immunosuppressed patients with herpesvirus infection.

Abstract

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.

• Authors: C W Young, R Schneider, B Leyland-Jones, D Armstrong, C T Tan, C Lopez, K A Watanabe, J J Fox, F S Philips
• Journal: Cancer research (Cancer Res) Vol. 43 Issue 10 Pg. 5006-9 (Oct 1983) ISSN: 0008-5472 [Print] United States
• PMID: 6309380 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• Cytarabine
• fiacitabine

Topics

• Antiviral Agents
• Cytarabine (analogs & derivatives, therapeutic use)
• Drug Evaluation
• Hematopoiesis (drug effects)
• Herpesviridae Infections (complications, drug therapy)
• Humans
• Immunosuppression Therapy
• Neoplasms (complications)