|
|
 Previous Article | Table of Contents | Next Article 
Topotecan, a topoisomerase I inhibitor, is active in the treatment of
myelodysplastic syndrome and chronic myelomonocytic leukemia
M Beran, H Kantarjian, S O'Brien, C Koller, M al-Bitar, S Arbuck, S Pierce, M Moore, JL Abbruzzese, M Andreeff, M Keating and E Estey
Department of Hematology, M.D. Anderson Cancer Center, Houston, TX 77030,
USA.
The aim of this study was to evaluate the activity of topotecan in patients
with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia
(CMML). Forty-seven patients with a diagnosis of MDS (n = 22) or CMML (n =
25) were treated. The median age was 66 years. Chromosomal abnormalities
were present in 70% and thrombocytopenia less than 50 x 10(3)/microL in
51%. Evaluation of outcome and of differences among subgroups was performed
according to standard methods; the criteria for response were those used
for acute leukemia. Topotecan was administered as 2 mg/ m2 by continuous
infusion over 24 hours daily for 5 days (10 mg/m2 per course) every 3 to 4
weeks until remission, then once every month for a maximum of 12 courses.
Thirteen patients (28%) achieved a complete response (CR) and six (13%) had
hematologic improvement. A CR was achieved in six of 22 patients with MDS
(27%) and in seven of 25 with CMML (28%). All eight patients who presented
with cytogenetic abnormalities (five chromosome 5 or 7 abnormalities) who
achieved CR were cytogenetically normal in CR. Characteristics for which
there was evidence of association with a higher response rate were lack of
prior chemotherapy, less than 10% marrow monocytes, and absence of RAS
oncogene mutations. In contrast, CR rates were similar in patients with or
without abnormal karyotypes. Mucositis occurred in 64% of patients (severe
in 19%) and diarrhea in 32% (severe in 13%). Febrile episodes occurred in
85% of patients and documented infections in 47%. With a median follow-up
duration of 8 months, the 12-month survival rate was 38%, median survival
time 10.5 months, and median remission duration 7.5 months. We conclude
that topotecan has significant activity in MDS and CMML, with acceptable
side effects. Future studies will investigate topotecan combined with
topoisomerase II reactive agents, cytarabine, or hypomethylating agents
(azacytidine and decitabine).
Volume 88,
Issue 7,
pp. 2473-2479,
10/01/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Chang, B. E. Storer, B. L. Scott, E. M. Bryant, H. M. Shulman, M. E. Flowers, B. M. Sandmaier, R. P. Witherspoon, R. A. Nash, J. E. Sanders, et al.
Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders
Blood,
August 15, 2007;
110(4):
1379 - 1387.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W. Cooper, G. J. Veal, T. Radivoyevitch, M. J. Tilby, H. J. Meyerson, H. M. Lazarus, O. N. Koc, R. J. Creger, G. Pearson, G. M. Nowell, et al.
A Phase I and Pharmacodynamic Study of Fludarabine, Carboplatin, and Topotecan in Patients With Relapsed, Refractory, or High-Risk Acute Leukemia
Clin. Cancer Res.,
October 15, 2004;
10(20):
6830 - 6839.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Beran, S. O'Brien, D. A. Thomas, H. T. Tran, J. E. Cortes-Franco, F. Giles, E. Estey, and H. M. Kantarjian
Phase I Study of Oral Topotecan in Hematological Malignancies
Clin. Cancer Res.,
September 15, 2003;
9(11):
4084 - 4091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. J. Giles, J. E. Cortes, D. A. Thomas, G. Garcia-Manero, S. Faderl, S. Jeha, R. L. De Jager, and H. M. Kantarjian
Phase I and Pharmacokinetic Study of DX-8951f (Exatecan Mesylate), a Hexacyclic Camptothecin, on a Daily-Times-Five Schedule in Patients with Advanced Leukemia
Clin. Cancer Res.,
July 1, 2002;
8(7):
2134 - 2141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. R. Silverman, E. P. Demakos, B. L. Peterson, A. B. Kornblith, J. C. Holland, R. Odchimar-Reissig, R. M. Stone, D. Nelson, B. L. Powell, C. M. DeCastro, et al.
Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B
J. Clin. Oncol.,
May 15, 2002;
20(10):
2429 - 2440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. L. Furman, C. F. Stewart, M. Kirstein, J. L. Kepner, M. L. Bernstein, F. Kung, T. J. Vietti, C. P. Steuber, D. L. Becton, S. Baruchel, et al.
Protracted Intermittent Schedule of Topotecan in Children With Refractory Acute Leukemia: A Pediatric Oncology Group Study
J. Clin. Oncol.,
March 15, 2002;
20(6):
1617 - 1624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Garcia-Carbonero and J. G. Supko
Current Perspectives on the Clinical Experience, Pharmacology, and Continued Development of the Camptothecins
Clin. Cancer Res.,
March 1, 2002;
8(3):
641 - 661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Witherspoon, H. J. Deeg, B. Storer, C. Anasetti, R. Storb, and F. R. Appelbaum
Hematopoietic Stem-Cell Transplantation for Treatment-Related Leukemia or Myelodysplasia
J. Clin. Oncol.,
April 15, 2001;
19(8):
2134 - 2141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Cheson, J. M. Bennett, H. Kantarjian, A. Pinto, C. A. Schiffer, S. D. Nimer, B. Lowenberg, M. Beran, T. M. de Witte, R. M. Stone, et al.
Report of an international working group to standardize response criteria for myelodysplastic syndromes
Blood,
December 1, 2000;
96(12):
3671 - 3674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Vey, F. J. Giles, H. Kantarjian, T. L. Smith, M. Beran, and S. Jeha
The Topoisomerase I Inhibitor DX-8951f Is Active in a Severe Combined Immunodeficient Mouse Model of Human Acute Myelogenous Leukemia
Clin. Cancer Res.,
February 1, 2000;
6(2):
731 - 736.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. Hellstrom-Lindberg, C. Willman, A. J. Barrett, and Y. Saunthararajah
Achievements in Understanding and Treatment of Myelodysplastic Syndromes
Hematology,
January 1, 2000;
2000(1):
110 - 132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Beran, E. Estey, S. O'Brien, J. Cortes, C. A. Koller, F. J. Giles, S. Kornblau, M. Andreeff, N. Vey, S. R. Pierce, et al.
Topotecan and Cytarabine Is an Active Combination Regimen in Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia
J. Clin. Oncol.,
September 1, 1999;
17(9):
2819 - 2819.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Heaney and D. W. Golde
Myelodysplasia
N. Engl. J. Med.,
May 27, 1999;
340(21):
1649 - 1660.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-F. Heron
Topotecan: An Oncologist's View
Oncologist,
December 1, 1998;
3(6):
390 - 402.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. E. Frankel, M. Lilly, R. Kreitman, D. Hogge, M. Beran, M. H. Freedman, P. D. Emanuel, C. McLain, P. Hall, E. Tagge, et al.
Diphtheria Toxin Fused to Granulocyte-Macrophage Colony-Stimulating Factor Is Toxic to Blasts From Patients With Juvenile Myelomonocytic Leukemia and Chronic Myelomonocytic Leukemia
Blood,
December 1, 1998;
92(11):
4279 - 4286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Winter and M. Weller
Potentiation of CD95L-Induced Apoptosis of Human Malignant Glioma Cells by Topotecan Involves Inhibition of RNA Synthesis but Not Changes in CD95 or CD95L Protein Expression
J. Pharmacol. Exp. Ther.,
September 1, 1998;
286(3):
1374 - 1382.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
V. Relias and J. Andrew Skirvin
Review : Topoisomerase I inhibitors: 1. Topotecan
Journal of Oncology Pharmacy Practice,
December 1, 1997;
3(4):
173 - 185.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. B. Ewesuedo and M. J. Ratain
Topoisomerase I Inhibitors
Oncologist,
December 1, 1997;
2(6):
359 - 364.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Kouides and J. M. Bennett
Understanding the Myelodysplastic Syndromes
Oncologist,
December 1, 1997;
2(6):
389 - 401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
