Phase II study of topotecan and thalidomide in patients with high-risk myelodysplastic syndromes.

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.
AuthorsAzra Raza, Laurie Lisak, Jennifer Billmeier, Hassan Pervaiz, Muhammad Mumtaz, Samreen Gohar, Khalid Wahid, Naomi Galili
JournalLeukemia & lymphoma (Leuk Lymphoma) Vol. 47 Issue 3 Pg. 433-40 (Mar 2006) ISSN: 1042-8194 [Print] England
PMID16396766 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Thalidomide
  • Topotecan
  • Aged
  • Anemia, Refractory, with Excess of Blasts (drug therapy, pathology)
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Drug Tolerance
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes (drug therapy, pathology)
  • Risk Factors
  • Thalidomide (administration & dosage, adverse effects, therapeutic use)
  • Time Factors
  • Topotecan (administration & dosage, adverse effects, therapeutic use)
  • Treatment Outcome

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