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Results of Topotecan Single-Agent Therapy in Patients with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia
| Content Provider | Scilit |
|---|---|
| Author | O'brien, Susan M. Beran, Miloslav Estey, Elihu Giles, Francis J. Roller, Charles A. Kornblau, Steven Keating, Michael Kantarjian, Hagop M. |
| Copyright Year | 1998 |
| Abstract | The activity of topotecan was evaluated in patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). Sixty patients with a diagnosis of MDS (n=30) or CMML (n=30) were treated. Their median age was 66 years, with 50 patients (83%) being over 60 years of age at time of study entry. Chromosomal abnormalities were present in 50% of patients and thrombocytopenia of less than 50 × $10^{9}$/L in 50%. Topotecan was administered as 2 $mg/m^{2}$ by continuous infusion over 24 hours daily for five days (10 $mg/m^{2}$ per course) every 4 to 6 weeks for two courses, then at maximum tolerated dose level (1-2 $mg/m^{2}$by continuous infusion over 24 hours daily for five days) once every 4-8 weeks for a maximum of 12 courses. Evaluation of outcome and of differences among subgroups was performed according to standard methods; the criteria for response were those used for acute leukemia. Nineteen patients (31%) achieved a complete response (CR). A CR was achieved in 11 of 30 patients with MDS (37%) and in eight of 30 with CMML (27%). A CR was achieved in 10 of 23 patients with previously untreated MDS (43%). Eight of 11 patients who presented with cytogenetic abnormalities (five of which involved chromosome 5 and/or 7 abnormalities) and achieved CR, were evaluated cytogenetically in CR: all were cytogenetically normal in CR. Characteristics associated with a higher CR rate were lack of previous chemotherapy, absence of ras oncogene mutations, and presence of less than 10% monocytes in either peripheral blood or bone marrow. In contrast, CR rates were similar by different agent groups, by different karyotype abnormalities, and by other pre-therapy peripheral blood counts. Non-myelosuppressive side effects were mucositis in 67% of patients (severe [grade 3-4] 23%), diarrhea in 38% (severe 17%), and nausea and vomiting in 28% (severe 5%). Febrile episodes during neutropenia occurred in 85% of patients and documented infections in 47%. Mortality in the first four weeks was 20%. With a median follow-up duration of 31 months, the 12 month survival rate was 38%, median survival time 10.5 months, and median remission duration 7.5 months. In summary, topotecan has significant single-agent activity in MDS and CMML. Complete responses associated with topotecan therapy often involve the disappearance of abnormal, poor-prognosis karyotypes, which is particularly encouraging. Future strategies to optimize topotecan's role include combination regimens with topoisomerase II reactive agents, cytarabine, or hypomethylating agents (azacytidine and decitabine). |
| Related Links | https://www.tandfonline.com/doi/pdf/10.3109/10428199809057611 |
| Ending Page | 531 |
| Page Count | 11 |
| Starting Page | 521 |
| ISSN | 10428194 |
| e-ISSN | 10292403 |
| DOI | 10.3109/10428199809057611 |
| Journal | Leukemia & Lymphoma |
| Issue Number | 5-6 |
| Volume Number | 31 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 1998-01-01 |
| Access Restriction | Open |
| Subject Keyword | Oncology Topotecan Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia |
| Content Type | Text |
| Resource Type | Article |
| Subject | Hematology Cancer Research Oncology |
