Clinical experience with fludarabine in leukaemia.
Fludarabine (Fludara) is a new purine analogue that was first entered into clinical trials in 1982. Results of initial studies with high dosages (> 96 mg/m2/day for 5 to 7 days) of fludarabine in acute leukaemia showed significant cytoreductive activity but a high incidence of severe irreversible neurotoxicity. The results of subsequent studies with lower dosages of 25 to 30 mg/m2/day for 5 days in chronic lymphocytic leukaemia (CLL) and low grade lymphomas have shown this regimen to be effective and safe, with almost no significant neurotoxicity. At present, the major role of fludarabine in leukaemia is in the management of CLL. In previously treated patients with CLL, responses are obtained in more than 50% of patients, with two-thirds of those responses being complete remissions according to the National Cancer Institute Working Group (NCIWG) criteria for complete response and partial response. The major causes of morbidity associated with fludarabine in CLL are infections and febrile episodes. These occur more frequently in previously treated patients and those with advanced stage of disease. Myelosuppression is dose limiting and a small proportion of patients with CLL develop moderate to severe and sometimes protracted myelosuppression. Administration of combined fludarabine and cytarabine (cytosine arabinoside; ara-C) alone (FA regimen) or together with granulocyte colony-stimulating factor (FLAG regimen) produced high response rates in previously treated refractory patients with acute leukaemia and previously untreated patients with acute myelogenous leukaemia or myelodysplastic syndrome. The wide range of biochemical and biological activities of fludarabine suggests that it will have an expanding role in future combinations in the treatment of both acute and chronic leukaemias.
Keating
M J
MJ
University of Texas M.D. Anderson Cancer Center, Houston.
Estey
E
E
O'Brien
S
S
Kantarjian
H
H
Robertson
L E
LE
Plunkett
W
W
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine