Phase I and pharmacokinetic study of arabinofuranosyl-5-azacytosine (fazarabine, NSC 281272)

• Published in: Cancer research (Chicago, Ill.) Vol. 50; no. 4; pp. 1220 - 1225
• Main Authors: SURBONE, A, FORD, H. JR, KELLEY, J. A, BEN-BARUCH, N, THOMAS, R. V, FINE, R, COWAN, K. H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-02-1990
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Azacitidine - administration & dosage; Azacitidine - adverse effects; Azacitidine - pharmacokinetics; Azacitidine - therapeutic use; Biological and medical sciences; Chemotherapy; Clinical Trials as Topic; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukopenia - chemically induced; Male; Medical sciences; Middle Aged; Neoplasms - blood; Neoplasms - drug therapy; Neutropenia - chemically induced; Pharmacology. Drug treatments; Thrombocytopenia - chemically induced; Antineoplastic agent; Therapeutic efficiency; Human; Refractory; Chemotherapy; Treatment; Intravenous administration; Phase I trial; Tumor; Effective dose; Malignant tumor; Pharmacokinetics
• ISSN: 0008-5472; 1538-7445

A Phase I clinical trial of 1-beta-D-arabinofuranosyl-5-azacytosine (ara-AC or fazarabine) given as a 72-h continuous infusion on a 21-day cycle was conducted in 27 adult patients with refractory cancer. The major toxicity was reversible granulocytopenia and thrombocytopenia. Dose-limiting toxicity was observed at a dose rate of 1.96 mg/m2/h in which Grade IV leukopenia (WBC less than 1,000/mm3) occurred in 4 of 11 patients and Grade IV thrombocytopenia (platelets less than 25,000/mm3) occurred in 3 of 11 patients. Plasma steady-state levels ranged from 0.13 to 0.6 microM for doses of 1.25 to 5.94 mg/m2/h. Mean total body clearance was 647 ml/min/m2. Minor clinical responses were seen in one patient with testicular cancer, one patient with colon cancer, one patient with breast cancer, and one patient with acute nonlymphocytic leukemia. Another patient with adenocarcinoma of unknown primary had stable disease during 13 cycles of therapy. Based on the results of this study, the recommended dose for Phase II studies of 1-beta-D-arabinofuranosyl-5-azacytosine administered as a 72-h continuous infusion is 2.0 mg/m2/h (48 mg/m2/day).