OBJECTIVES: A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy and to correlate angiogenesis biomarker expression with clinical outcome. METHODS: Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens. RESULTS: Twenty-four of twenty-seven patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose, and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free>or=6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival were 1.7 months and 6.3 months, respectively. No grade 4 toxicities were observed. Common grade 3 toxicities included hematologic (n=3), cardiovascular (n=3), constitutional (n=3), and neurologic (n=4). Thalidomide did not decrease VEGF or bFGF levels but reduced sEPCR levels in serum. Elevated plasma vascular endothelial growth factor levels were associated with increased risk of progression and death. CONCLUSIONS: Thalidomide demonstrated limited ability to delay progression (as measured by PFS at 6 months), produce objective responses, or reduce angiogenic marker levels in chemotherapy refractory endometrial cancer. VEGF level appears to be prognostically significant in such patients, independent of thalidomide treatment.
OBJECTIVES: A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy and to correlate angiogenesis biomarker expression with clinical outcome. METHODS: Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens. RESULTS: Twenty-four of twenty-seven patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose, and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free>or=6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival were 1.7 months and 6.3 months, respectively. No grade 4 toxicities were observed. Common grade 3 toxicities included hematologic (n=3), cardiovascular (n=3), constitutional (n=3), and neurologic (n=4). Thalidomide did not decrease VEGF or bFGF levels but reduced sEPCR levels in serum. Elevated plasma vascular endothelial growth factor levels were associated with increased risk of progression and death. CONCLUSIONS:Thalidomide demonstrated limited ability to delay progression (as measured by PFS at 6 months), produce objective responses, or reduce angiogenic marker levels in chemotherapy refractory endometrial cancer. VEGF level appears to be prognostically significant in such patients, independent of thalidomide treatment.
Authors: A Giatromanolaki; E Sivridis; R Brekken; P E Thorpe; P Anastasiadis; K C Gatter; A L Harris; M I Koukourakis Journal: Cancer Date: 2001-11-15 Impact factor: 6.860
Authors: Ahmedin Jemal; Rebecca Siegel; Elizabeth Ward; Taylor Murray; Jiaquan Xu; Carol Smigal; Michael J Thun Journal: CA Cancer J Clin Date: 2006 Mar-Apr Impact factor: 508.702
Authors: George L Scheffer; Marcel J Flens; Sandra Hageman; Miguel A Izquierdo; Robert H Shoemaker; Rik J Scheper Journal: Eur J Cancer Date: 2002-07 Impact factor: 9.162
Authors: Kathleen N Moore; Michael W Sill; Meaghan E Tenney; Christopher J Darus; David Griffin; Theresa L Werner; Peter G Rose; Robert Behrens Journal: Gynecol Oncol Date: 2015-07-11 Impact factor: 5.482
Authors: Don S Dizon; Michael W Sill; Jeanne M Schilder; Kathryn F McGonigle; Zia Rahman; David S Miller; David G Mutch; Kimberly K Leslie Journal: Gynecol Oncol Date: 2014-10-13 Impact factor: 5.482
Authors: Brian M Slomovitz; Yunyun Jiang; Melinda S Yates; Pamela T Soliman; Taren Johnston; Maureen Nowakowski; Charles Levenback; Qian Zhang; Kari Ring; Mark F Munsell; David M Gershenson; Karen H Lu; Robert L Coleman Journal: J Clin Oncol Date: 2015-01-26 Impact factor: 44.544
Authors: Halla S Nimeiri; Amit M Oza; Robert J Morgan; Gregory Friberg; Kristen Kasza; Leonardo Faoro; Ravi Salgia; Walter M Stadler; Everett E Vokes; Gini F Fleming Journal: Gynecol Oncol Date: 2008-04-18 Impact factor: 5.482