TY - JOUR
T1 - Thalidomide therapy for myelofibrosis with myeloid metaplasia
AU - Thomas, Deborah A.
AU - Giles, Francis J.
AU - Albitar, Maher
AU - Cortes, Jorge E.
AU - Verstovsek, Srdan
AU - Faderl, Stefan
AU - O'Brien, Susan M.
AU - Garcia-Manero, Guillermo
AU - Keating, Michael J.
AU - Pierce, Sherry
AU - Zeldis, Jerome
AU - Kantarjian, Hagop M.
PY - 2006/5/1
Y1 - 2006/5/1
N2 - BACKGROUND. Thalidomide is a putative antiangiogenesis agent with activity in several hematologic malignancies. METHODS. Forty-four patients who had myelofibrosis with myeloid metaplasia received treatment with thalidomide in a Phase II clinical trial at a dose of 200 mg daily with escalation by 200 mg weekly until the best tolerated dose (maximum, 800 mg) was reached. RESULTS. Seventeen of 41 evaluable patients (41%) who received treatment for at least 15 days had a response. A complete response (without reversal of bone marrow fibrosis) was achieved in 4 patients (10%), a partial response was achieved in 4 patients (10%), and hematologic improvements in anemia, thrombopenia, and/or splenomegaly were observed in 9 patients (21%). Improvements in anemia occurred in 7 of 35 patients (20%) with hemoglobin levels <10.0 g/dL, and improvements in thrombopenia occurred in 5 of 24 patients (21%) with platelet counts <100 × 109/L. Five of 24 patients (21%) became transfusion- independent. Major or minor regression of splenomegaly was noted in 9 of 29 evaluable patients (31%), and complete regression was noted in 5 patients. Responders had a lower baseline median vascular endothelial growth factor levels (77.9 pg/mL vs. 97.7 pg/mL; P < .01) and higher median basis fibroblast growth factor levels (60.8 pg/mL vs. 37.4 pg/mL; P < .01) compared with nonresponders. Nine patients (22%) had deterioration that was attributed to thalidomide (resolved after withdrawal) with either progressive cytopenias or excessive proliferation. Two patients developed Grade 3 neutropenia with recovery and resumed therapy with dose reductions, and both later achieved a complete response. Dose-related toxicities included fatigue (50%), constipation (48%), rash or pruritis (37%), sedation (35%), peripheral edema (29%), tremors (23%), peripheral neuropathy (22%), and orthotasis (16%). CONCLUSIONS. Thalidomide warrants further evaluation in patients with MMM, particularly in combination regimens, along with the investigation of newer analogs.
AB - BACKGROUND. Thalidomide is a putative antiangiogenesis agent with activity in several hematologic malignancies. METHODS. Forty-four patients who had myelofibrosis with myeloid metaplasia received treatment with thalidomide in a Phase II clinical trial at a dose of 200 mg daily with escalation by 200 mg weekly until the best tolerated dose (maximum, 800 mg) was reached. RESULTS. Seventeen of 41 evaluable patients (41%) who received treatment for at least 15 days had a response. A complete response (without reversal of bone marrow fibrosis) was achieved in 4 patients (10%), a partial response was achieved in 4 patients (10%), and hematologic improvements in anemia, thrombopenia, and/or splenomegaly were observed in 9 patients (21%). Improvements in anemia occurred in 7 of 35 patients (20%) with hemoglobin levels <10.0 g/dL, and improvements in thrombopenia occurred in 5 of 24 patients (21%) with platelet counts <100 × 109/L. Five of 24 patients (21%) became transfusion- independent. Major or minor regression of splenomegaly was noted in 9 of 29 evaluable patients (31%), and complete regression was noted in 5 patients. Responders had a lower baseline median vascular endothelial growth factor levels (77.9 pg/mL vs. 97.7 pg/mL; P < .01) and higher median basis fibroblast growth factor levels (60.8 pg/mL vs. 37.4 pg/mL; P < .01) compared with nonresponders. Nine patients (22%) had deterioration that was attributed to thalidomide (resolved after withdrawal) with either progressive cytopenias or excessive proliferation. Two patients developed Grade 3 neutropenia with recovery and resumed therapy with dose reductions, and both later achieved a complete response. Dose-related toxicities included fatigue (50%), constipation (48%), rash or pruritis (37%), sedation (35%), peripheral edema (29%), tremors (23%), peripheral neuropathy (22%), and orthotasis (16%). CONCLUSIONS. Thalidomide warrants further evaluation in patients with MMM, particularly in combination regimens, along with the investigation of newer analogs.
KW - Agnogenic myaloid metaplasia
KW - Basic fibroblast growth factor
KW - Myelofibrosis
KW - Thalidomide
KW - Tumor necrosis factor α
KW - Vascular endothelial growth factor
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U2 - 10.1002/cncr.21827
DO - 10.1002/cncr.21827
M3 - Article
C2 - 16583431
AN - SCOPUS:33646336631
SN - 0008-543X
VL - 106
SP - 1974
EP - 1984
JO - cancer
JF - cancer
IS - 9
ER -
