Phase I clinical trial of fazarabine as a twenty-four-hour continuous infusion.

Abstract

A phase I trial of fazarabine (ara-AC, 1-beta-D-arabinofuranosyl-5-azacytosine, NSC 281272) administered as a 24-h continuous infusion was performed in 24 adults with solid tumor malignancies. The majority of patients had received prior marrow-suppressive therapy. Level 7 (54.5 mg/m2/h for 24 h) was the maximum tolerated dose since during 6 evaluable first courses, 2 episodes of grade 4 granulocytopenia and 3 episodes of grade 3 occurred. Moderate thrombocytopenia also occurred at level 7 with 3 episodes of grade 1 and 1 episode of grade 4 thrombocytopenia during 6 first course treatments. Minimal myelosuppression, principally leukopenia, was seen prior to level 7. The nadir WBC through 47 courses had a linear relationship with plasma steady-state concentrations of ara-AC. The only other toxicity noted was moderate nausea/vomiting, which did not appear to be dose related. Plasma steady-state concentrations of ara-AC were reached in all patients within 4-6 h and ranged from 1.1 microM (11 mg/m2/h for 24 h) to 7.5 microM (54.5 mg/m2/h for 24 h). The mean total body clearance of ara-AC for 47 courses, levels 1-7, was 592 +/- 147 (SD) ml/min/m2 which is similar to prior pharmacokinetic data from the 24-h and 72-h infusion trials of the Pediatric and Medicine Branches, respectively. There were no objective disease responses during the trial. The recommended adult phase II dose for a 24-h infusion of ara-AC is 45-50 mg/m2/h.

• Authors: H Bailey, K D Tutsch, R Z Arzoomanian, M B Tombes, D Alberti, J Bruggink, G Wilding
• Journal: Cancer research (Cancer Res) Vol. 51 Issue 4 Pg. 1105-8 (Feb 15 1991) ISSN: 0008-5472 [Print] United States
• PMID: 1705165 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• fazarabine
• Azacitidine

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, pharmacokinetics, toxicity)
• Azacitidine (administration & dosage, adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Humans
• Infusions, Intravenous
• Metabolic Clearance Rate
• Middle Aged
• Neoplasms (drug therapy)