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- W2440379957 abstract "Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are heterogeneous disorders for which there exist few active therapies and where the standard of care is still considered supportive. Identification of new effective therapies in MDS and CMML is a high priority for hematologic oncologists. We have evaluated the efficacy of single-agent topotecan, a topoisomerase I inhibitor, in patients with MDS (refractory anemia with excess blasts [RAEB] and refractory anemia with excess blasts in transformation [RAEB-T]) and CMML. Sixty patients (MDS = 30; CMML = 30) with a median age of 66 years were treated. Chromosomal abnormalities were present in half of the patients, as was thrombocytopenia. Topotecan was administered at 2 mg/m2 by continuous intravenous infusion over 24 hours daily for 5 days every 4 to 6 weeks until remission, followed by one course every 4 to 8 weeks for a maximum of 10 courses. Nineteen patients (32%) achieved a complete response (CR); seven had hematologic improvement. CRs were observed in 11 of 30 patients with MDS (37%) and eight of 30 patients with CMML (27%). Conversion to diploid karyotype was observed in eight patients with karyotypic abnormalities at diagnosis who later achieved a CR. History of prior chemotherapy and monocytosis was associated with poor prognosis. Mutation of the RAS oncogene was found in six CMML patients (20%), and none responded to topotecan therapy. The estimated 12-month survival rate was 33%, the median survival time was 9.3 months, and the median remission duration was 7 months. The most significant toxicities were gastrointestinal, including mucositis (67%; severe 23%) and diarrhea (38%; severe 17%). Febrile episodes were noted in 85% of the patients, while documented infection occurred in 47%. Topotecan has demonstrated significant single-agent activity in MDS and CMML with generally manageable side effects. Future studies will evaluate topotecan-based combination therapies with topoisomerase II reactive agents, cytarabine, alkylating agents, and hypomethylating agents." @default.
- W2440379957 created "2016-06-24" @default.
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- W2440379957 date "1998-07-01" @default.
- W2440379957 modified "2023-09-23" @default.
- W2440379957 title "Topotecan in the treatment of hematologic malignancies." @default.
- W2440379957 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9779879" @default.
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