Phase I Clinical Trial of Fazarabine as a Twenty-four-Hour Continuous Infusion 1
A phase I trial of fazarabine (araAC, l-0-D-arabinofuranosyl-5-azaeytusine, 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 Ã©valuablefirst 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 thrombo cytopenia during 6 first course treatments. Minimal myelosuppression, principally leukopenia, was seen prior to level 7. The nadir YVBCthrough 47 courses had a linear relationship with plasma steady-state concentra tions 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 MM(11 mg/m2/h for 24 h) to 7.5 MM(54.5 mg/m2/h for 24 h). The mean total body clearance of ara-AC for 47 courses, levels 17, was 592 Â±147 (SD) ml/iuin/nr which is similar to prior pharmacokinetic data from the 24-h and 72-h infusion trials of the Pediatrie and Medicine Branches, respectively. There were no objective disease re sponses during the trial. The recommended adult phase II dose for a 24h infusion of ara-AC is 45-50 mg/m2/h.