TY - JOUR
T1 - A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers
T2 - A Gynecologic Oncology Group study
AU - McMeekin, D. Scott
AU - Sill, Michael W.
AU - Benbrook, Doris
AU - Darcy, Kathleen M.
AU - Stearns-Kurosawa, Deborah J.
AU - Eaton, Lynne
AU - Yamada, S. Diane
N1 - Funding Information:
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469) and the GOG Statistical and Data Center (CA 37517). The following GOG member institutions participated in this study: Abington Memorial Hospital, University of Pennsylvania Cancer Center, University of North Carolina School of Medicine, Indiana University Medical Center, Tufts-New England Medical Center, Rush-Presbyterian-St. Luke's Medical Center, The Cleveland Clinic Foundation, State University of New York at Stony Brook, Cooper Hospital/University Medical Center, Columbus Cancer Council, MD Anderson, University of Oklahoma, University of Virginia, University of Chicago, Tacoma General Hospital, Case Western Reserve University, and Fletcher Allen Health Care.
PY - 2007/5
Y1 - 2007/5
N2 - 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 ≥ 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.
AB - 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 ≥ 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.
KW - GOG
KW - Refractory endometrial cancer angiogenesis biomarkers
KW - Thalidomide
UR - http://www.scopus.com/inward/record.url?scp=34247128217&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2007.01.019
DO - 10.1016/j.ygyno.2007.01.019
M3 - Article
C2 - 17306350
AN - SCOPUS:34247128217
SN - 0090-8258
VL - 105
SP - 508
EP - 516
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -