Phase I clinical trial of fludarabine phosphate (F-ara-AMP).
F-Ara-AMP (fludarabine phosphate) is an adenosine analogue that is resistant to deamination; it is a more potent cytotoxic compound than ara-A in experimental tumor systems. F-Ara-AMP was given by continuous IV infusion over 5 days once every 4 weeks to 27 evaluable adult patients with advanced cancer. The median Karnofsky performance status was 70% (range 50%-90%), and the median age was 58 years (range 41-74). In addition to adequate blood counts, a creatinine clearance of at least 60 ml/min was required. The initial dose level was 35 mg/m2/day. Dose-limiting myelosuppression was seen in the first patient. Subsequent patients were treated at lower doses. Myelosuppression was the only major toxicity. Leukopenia was generally more prominent than thrombocytopenia, but 2 patients experienced prolonged thrombocytopenia which prevented further therapy. Nausea was minimal, and neither renal nor neurologic toxicity was encountered. In patients with good renal function a dose of 25 mg/m2/day can be safely administered. However, because of apparent cumulative myelosuppressive effects a lower dose is more appropriate for patients who have had extensive prior chemotherapy or radiotherapy.
Casper
E S
ES
Mittelman
A
A
Kelson
D
D
Young
C W
CW
D000328:Adult; D000368:Aged; D001088:Arabinonucleotides / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000633:toxicity*
D001088:Arabinonucleotides; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate