Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders with a variable clinical course and prognosis. Treatment should be individualized based on the patient's age, subtype, percent blasts in the marrow, and cytogenetics. The use of the International Prognostic Scoring Index is helpful in assigning prognosis. The standard of care for low-risk patients is supportive care. Low-risk patients with symptomatic anemia should be considered for a trial of erythropoietin. The serum erythropoietin (EPO) level may help predict response to treatment. The treatment of the symptomatic and high-risk patient is unclear. Low-dose cytarabine, amifostine, and 5-azacitidine can induce responses in selected patients, but the duration of responses is short, and treatment does not appear to prolong survival. Intensive chemotherapy should be reserved for high-risk, younger patients. Topotecan and intermediate cytarabine appear to have an active regimen, but remissions are short. Younger patients who present with high-risk MDS without an antecedent history of MDS should receive intensive acute myeloid leukemia (AML) induction chemotherapy. Younger patients with high-risk MDS and an HLA-compatible donor should be offered an allogeneic stem cell transplant.
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PMID:Myelodysplastic syndromes. 1205 62

Topotecan has demonstrable activity in high-risk MDS and CMMoL. However, the significant toxicity of topotecan administered at a dose of 2mg/m2 i.v. daily for 5 days as a continuous infusion limits its use in older patients. Therefore, we studied topotecan 1.5mg/m2 per day i.v. over 2 h for three consecutive days in 20 patients with high-risk MDS (12 RAEB; 4 RAEB-T; 4 CMMoL). Cycles were given every 4-6 weeks. Fifteen patients were evaluable for response. Only one patient achieved a durable complete remission (CR). There were three deaths within the first cycle of therapy. Severe myelosuppression was the most common toxicity. Grades 3-4 infections were documented in four patients. We conclude that topotecan administered at this dose and schedule has no clinically significant activity.
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PMID:Phase II study of low-dose topotecan in myelodysplastic syndromes: a Hoosier Oncology Group (HOG) study. 1506 95

Topotecan, a topoisomerase-I inhibitor is an active drug in the treatment of AML and MDS. To evaluate its toxicity and efficacy in a combination regimen with cytarabine, we conducted a clinical phase I/II trial in patients with relapsed acute myeloid leukemia (AML) or relapsed or newly diagnosed MDS RAEB, RAEB-t or CMML. Twenty-one patients (11 AML, 10 MDS/CMML) entered the study and were treated with 1.25 mg/m2 topotecan as continuous intravenous infusion daily for 5 days and cytarabine 1.0 g/m2 by infusion over 2 h daily for 5 days (TA). Cycles were repeated on day 28. The median observation time was 131 weeks (range: 36-196 weeks). A total of 37 cycles of TA were administered. In 1 patient, the dose of TA had to be reduced and in 1 patient, there was a treatment delay for the second cycle, both because of hematologic toxicity. The most frequent non-hematologic side-effect of TA was fever, which occurred in 17 patients (89%) with temperatures over 38 degrees C. None of the patients died due to any treatment-related toxicities, but 2 patients (10%) died within 1 month due to disease progression. A CR was achieved in 7 patients (33%), 3 of whom were MDS and 4 AML. A partial remission was reported in 8 patients (38%), no change of disease in 2 patients (10%) and progressive disease in 4 patients (19%). The median remission duration was 18 weeks (range 2-161 weeks) for MDS patients and 11 weeks (range 2-49 weeks) for AML patients. The time to progression for patients of 60 years and older (n = 10) was 16 weeks (range 2-49 weeks) and the survival was 32 weeks (range 2-119 weeks). TA is a feasible and efficacious chemotherapeutic combination for the treatment of MDS RAEB, RAEB-t, CMML and AML. For patients of 60 years and older, this regimen is also a safe option.
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PMID:Phase I/II clinical study of topotecan and cytarabine in patients with myelodysplastic syndrome, chronic myelomonocytic leukemia and acute myeloid leukemia. 1516 Sep 42

Topotecan (Hycamtin) is a water soluble semisynthetic analogue of the alkaloid camptothecin which has antitumour activity in preclinical models in vitro and in vivo. A range of Phase I studies has been performed and a daily x 5 iv. schedule, which showed most promising evidence of activity, was selected for extensive clinical evaluation. To date, topotecan has been shown to be active in a number of malignancies, including metastatic ovarian cancer, recurrent small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), breast cancer, colorectal cancer and myelodysplastic syndrome. In ovarian cancer, response rates of around 15% were identified in patients who had failed standard chemotherapy, and in a randomised, comparative study with paclitaxel response rates of 20% (topotecan) and 13% (paclitaxel) were observed. In addition, overall time to progression was impressive at 23 weeks (topotecan) compared with 14 weeks (paclitaxel). In recurrent SCLC, topotecan has shown good activity in sensitive patients with a response rate of 39%, although the response rate in refractory patients was considerably lower (7%). Median survival of all patients was 5.4 months, acceptable for this difficult clinical scenario. Topotecan is well-tolerated in the majority of patients and subjective toxicities are uncommon. The principal side-effect is myelosuppression, mainly neutropenia. Serious clinical sequelae are relatively uncommon and non-cumulative. Nonhaematological toxicities are generally mild and not dose-limiting. In clinical use, topotecan has exhibited activity in multiple tumour types, with a side-effect profile that is predictable and manageable. The drug is under evaluation in other tumour types and in combination chemotherapy regimens.
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PMID:Topotecan, an active new antineoplastic agent: review and current status. 1598 23


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