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: Azra Raza, Laurie Lisak, Jennifer Billmeier, Hassan Pervaiz, Muhammad Mumtaz, Samreen Gohar, Khalid Wahid, Naomi Galili
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 47 Issue 3 Pg. 433-40 (Mar 2006) ISSN: 1042-8194 [Print] United States
• PMID: 16396766 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Thalidomide
• Topotecan

Topics

• 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