ABSTRACT
The haloadenine nucleotide fludarabine phosphate was first synthesized by J.A. Montgomery and coworkers in 1969 and is one of the lead compounds of a new generation of nucleoside analogs. The mechanisms implicated in drug resistance to fludarabine phosphate have not been fully characterized. Low cellular concentrations of deoxycytidine kinase will lead to low drug activation rates. The antitumor activity of fludarabine phosphate has been studied against all major tumor types in clinical phase II trials. Clinical phase I studies with fludarabine phosphate revealed important information both for the compound itself and for principles of drug development in general. Myelosuppression has been the dose-limiting toxicity in clinical phase I and II trials in patients with solid tumors and was more pronounced than predicted from the mouse 10% lethal dose. Further clinical development of fludarabine phosphate will focus on how this agent may be integrated into the presently available therapeutic armamentarium.
