Phase I trial of 1-(2'-deoxy-2'-fluoro-1-β-D-arabinofuranosyl)-5-methyluracil (FMAU) Journal Article
| Authors: | Fanucchi, M. P.; Leyland-Jones, B.; Young, C. W.; Burchenal, J. H.; Watanabe, K. A.; Fox, J. J. |
| Article Title: | Phase I trial of 1-(2'-deoxy-2'-fluoro-1-β-D-arabinofuranosyl)-5-methyluracil (FMAU) |
| Abstract: | 1-(2'-Deoxy-2'-fluoro-1-β-D-arabinofuranosyl)-5-methyluracil (FMAU), a new pyrimidine nucleoside, is of potential clinical interest both as an anticancer and as an antiviral drug. FMAU is active in vitro and in vivo against P815 and L1210 cell lines resistant to cytarabine. Moreover, in mice inoculated ic with herpes simplex virus Type II, FMAU is 100-fold more potent than vidarabine or acyclovir. We have conducted a phase I trial of FMAU in 17 patients with advanced cancer. The dose levels studied were 2, 4, 8, 16, 32, 64, and 128 mg/m2/day iv for 5 days. The dose-limiting toxic effect was drug-induced central nervous system dysfunction. Although 32 mg/m2/day for 5 days produced only transient, mild symptoms, severe encephalopathy with extrapyramidal dysfunction occurred at 64 and 128 mg/m2/day for 5 days and contributed to two deaths. No toxicity was observed at < 32 mg/m2. A dose of 32 mg/m2/day for 5 days is suggested for phase II study. Because of its potent and selective antiviral activity, future trials of low doses of FMAU in immunosuppressed patients with herpes virus infections are under consideration. |
| Keywords: | adult; cancer chemotherapy; clinical article; aged; middle aged; carcinoma, squamous cell; drug efficacy; antineoplastic agents; neurotoxicity; neoplasms; nausea; vomiting; lung neoplasms; extrapyramidal symptom; brain disease; arabinofuranosyluracil; antivirus agent; drug dose; leukocyte count; phase 1 clinical trial; drug therapy; toxicity; adverse drug reaction; therapy; uridine; intravenous drug administration; platelet count; carcinoma, small cell; nervous system; drug evaluation; intoxication; herpes virus infection; central nervous system diseases; new drug; pyrimidine nucleoside; clevudine; humans; human; male; female; priority journal; article |
| Journal Title: | Cancer Treatment Reports |
| Volume: | 69 |
| Issue: | 1 |
| ISSN: | 0361-5960 |
| Publisher: | National Cancer Institute |
| Date Published: | 1985-01-01 |
| Start Page: | 55 |
| End Page: | 59 |
| Language: | English |
| PUBMED: | 2981621 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 26 October 2021 -- Source: Scopus |
