FLUDARABINE FOR TREATMENT OF ADULT ACUTE MYELOGENOUS LEUKEMIA

The success of fludarabine as a single agent for therapy of chronic lymphocytic leukemia suggested its use in other leukemias such as adult acute myelogenous leukemia. Because doses that are tolerated in the clinic were not effective in the treatment of acute myelogenous leukemia, our approach was to combine low dose fludarabine with other active agents such as arabinosylcytosine (ara-C). This is also based on the rationale that fludarabine pretreatment modulates the metabolism of ara-C resulting in potentiation of the accumulation of its triphosphate. Improved response rates and clinical efficacy of this combination further suggested combining this couplet with DNA damaging agents, because the active triphosphates of both these analogs inhibit replication and repair processes of DNA synthesis.