title: Phase II study of topotecan and thalidomide in patients with high-risk myelodysplastic syndromes.
abstract: This phase II trial investigated the safety and preliminary efficacy of a topotecan/thalidomide combination therapy in patients with myelodysplastic syndrome who had refractory anemia with excess blasts (RAEB), RAEB with transformation, or chronic myelomonocytic anemia. Patients received three 21-day cycles of topotecan 1.25 mg/m(2) on days 1-5, which was repeated for two additional cycles in patients whose bone marrow blast percentages did not decrease. Oral thalidomide was then started at 100 mg/day (with the dose escalated up to 300 mg/day if well tolerated) for up to 1 year. Patients were monitored throughout the trial for hematologic and clinical adverse events, and efficacy was assessed using International Working Group (IWG) criteria. Forty-five patients, mostly elderly (median age 68 years; range 52-79 years), were enrolled. Therapy was generally well tolerated compared to high-dose chemotherapy. Three patients died from disease progression/infections during topotecan therapy, and four patients discontinued topotecan because of high-grade neutropenia (two patients), syncope (one patient), or hip surgery (one patient). Of 24 patients who received thalidomide, three discontinued because of treatment-related toxicity. Thirty-eight patients were evaluable for response: nine (24%) had hematologic improvement and 13 (34%) had stable disease. Responses occurred in patients with all disease subtypes. Six patients achieved transfusion independence, and one patient had a trilineage response. Approximately one-third of the patients had decreases in bone marrow blasts of 50%. Therefore, a topotecan and thalidomide combination therapy is promising, although further studies are needed to determine the optimum doses and schedule.
authors.affiliation: The Radhey Khanna Center for MDS Research, University of Massachusetts Medical Center, Worcester, MA 01605, USA. azra.raza@umass.edu
authors.forename: Azra
authors.initials: A
authors.lastname: Raza
authors.forename: Laurie
authors.initials: L
authors.lastname: Lisak
authors.forename: Jennifer
authors.initials: J
authors.lastname: Billmeier
authors.forename: Hassan
authors.initials: H
authors.lastname: Pervaiz
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mumtaz
authors.forename: Samreen
authors.initials: S
authors.lastname: Gohar
authors.forename: Khalid
authors.initials: K
authors.lastname: Wahid
authors.forename: Naomi
authors.initials: N
authors.lastname: Galili
mesh_terms: D000368:Aged; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D019772:Topotecan