THE EXPANDING ROLE OF FLUDARABINE IN HEMATOLOGIC MALIGNANCIES

被引:22
作者
KEATING, MJ
OBRIEN, S
ROBERTSON, LE
KANTARJIAN, H
DIMOPOULOS, M
MCLAUGHLIN, P
CABANILLAS, F
GREGOIRE, V
YINGYANG, L
GANDHI, V
ESTEY, E
PLUNKETT, W
机构
[1] Departments of Hematology, Medical Oncology, and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX
关键词
FLUDARABINE; CHRONIC LYMPHOCYTIC LEUKEMIA; LOW GRADE LYMPHOMA; LYMPHOID MALIGNANCIES; ACUTE MYELOGENOUS LEUKEMIA; MYELODYSPLASTIC SYNDROME; RADIATION SENSITIZER;
D O I
10.3109/10428199409052690
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The major clinical experience with fludarabine has been obtained in patients with chronic lymphocytic leukemia (CLL). In the initial studies in previously treated patients with CLL, the complete and partial response rate (CR + PR) was over 50%, and in previously untreated patients with CLL, a CR + PR rate of 75-80% was noted with or without the addition of prednisone. Subsequent clinical trials have also demonstrated major activity with fludarabine in Waldenstrom's macroglobulinemia. Fludarabine was noted to be an active agent in indolent lymphoma in phase LIII studies. Approximately 60% of patients with follicular lymphoma respond to fludarabine when it is administered as a single agent. Many of these remissions are complete remissions despite patients having received extensive prior therapy. Combination programs are being developed for application in CLL and indolent lymphoma. Because of the activity of fludarabine in inhibiting DNA repair, it has been combined with cisplatinum and cytosine arabinoside and plans are in place to explore the radiation sensitizing effect of fludarabine in clinical trials. A combination of fludarabine plus ara-C is now being used in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) and a combination of fludarabine, ara-C, and G-CSF (FLAG) has been combined with idarubicin for the management of these conditions. Many of these activities of fludarabine are associated with its interaction with many enzymes which are important in DNA and RNA metabolism and in DNA repair. It is anticipated that these actions will be explored in a wider range of studies subsequently.
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页码:11 / 16
页数:6
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共 37 条
[1]  
Grever M.R., Leiby J., Kraut E., Metz E., Neidhart J., Balcerzak S., Malspeis L., A comprehensive phase I and II clinical investigations of fludarabine phosphate, Semin. Oncol., 17, Suppl 8, pp. 39-48, (1990)
[2]  
Von Hoff D.D., Phase I clinical trials with fludarabine phosphate, Semin. Oncol., 17, pp. 33-38, (1990)
[3]  
Grever M.R., Coltman C.A., Files J.C., Fludarabine monophosphate in chronic lymphocytic leukemia, Blood, 68, (1986)
[4]  
Keating M.J., Kantarjian H., O'Brien S., Fludarabine: A new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia, J. Clin. Oncol, 9, pp. 44-49, (1991)
[5]  
Keating M.J., Kantarjian H., Talpaz M., Fludarabine: A new agent with major activity against chronic lymphocytic leukemia, Blood, 74, pp. 19-25, (1989)
[6]  
Redman J.R., Cabanillas F., Velasquez W.S., Phase II trial of fludarabine phosphate in lymphoma: An effective new agent in low-grade lymphoma, J. Clin. Oncol, 10, pp. 790-794, (1992)
[7]  
Hochster H.S., Kim K., Green M.D., Activity of fludarabine in previously treated non-Hodgkin's low-grade lymphoma: Results of an Eastern Cooperative Oncology Group study, J. Clin. Oncol, 10, pp. 28-32, (1992)
[8]  
Plunkett W., Huang P., Gandhi V., Metabolism and action of fludarabine phosphate, Semin. Oncol, 17, pp. 3-17, (1990)
[9]  
Grever M.R., Kopecky K.J., Coltman C.A., Files J.C., Greenberg B.R., Fludarabine monophosphate: A potentially useful agent in chronic lymphocytic leukemia, Nouvell Revue Francaise d'Hematologic, 30, pp. 457-459, (1988)
[10]  
Cheson B.D., Bennett J.M., Rai K.R., Grever M.R., Kay N.E., Schiffer C.A., Oken M.M., Keating M.J., Boldt D.H., Kempin S.J., Foon K.A., Guidelines for clinical protocols for chronic lymphocytic leukemia: Recommendations of the National Cancer Institute Sponsored Working Group, Am. J. Hematol., 29, pp. 152-163, (1988)