Phase I clinical trial of fludarabine phosphate (F-ara-AMP)

Summary 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.Supported by CCPP grant CA-05826 and Contract NO1-CM-27546 from the National Cancer Institute, National Institutes of Health, Bethesda, Md. The content of this paper was presented in part at the 76^th meeting of the American Association for Cancer Research, Toronto, 1984