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Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia.

Abstract
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).
AuthorsM Beran, H Kantarjian, S O'Brien, C Koller, M al-Bitar, S Arbuck, S Pierce, M Moore, J L Abbruzzese, M Andreeff, M Keating, E Estey
JournalBlood (Blood) Vol. 88 Issue 7 Pg. 2473-9 (Oct 01 1996) ISSN: 0006-4971 [Print] United States
PMID8839838 (Publication Type: Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Neoplasm Proteins
  • Topoisomerase I Inhibitors
  • Topotecan
  • Camptothecin
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents (adverse effects, pharmacology, therapeutic use)
  • Camptothecin (adverse effects, analogs & derivatives, pharmacology, therapeutic use)
  • Diarrhea (chemically induced)
  • Female
  • Fever (chemically induced)
  • Follow-Up Studies
  • Genes, ras
  • Humans
  • Leukemia, Myelomonocytic, Chronic (drug therapy, enzymology, genetics, mortality)
  • Life Tables
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes (drug therapy, enzymology, genetics, mortality)
  • Neoplasm Proteins (antagonists & inhibitors)
  • Remission Induction
  • Stomatitis (chemically induced)
  • Survival Analysis
  • Survival Rate
  • Topoisomerase I Inhibitors
  • Topotecan
  • Treatment Outcome

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