PMID- 17597196 OWN - NLM STAT- MEDLINE DCOM- 20071011 LR - 20171116 IS - 0090-8258 (Print) IS - 0090-8258 (Linking) VI - 106 IP - 3 DP - 2007 Sep TI - A phase II trial of thalidomide in patients with refractory leiomyosarcoma of the uterus and correlation with biomarkers of angiogenesis: a gynecologic oncology group study. PG - 596-603 AB - OBJECTIVES: To evaluate the efficacy and adverse events (AEs) of thalidomide in previously treated, measurable, persistent or recurrent leiomyosarcoma (LMS) of the uterus, and to explore associations between angiogenic markers and treatment or clinical outcome. METHODS: Eligible, consenting patients were treated until disease progression or toxicity intervened with daily starting dose of 200 mg thalidomide/day that was increased by 200 mg every 2 weeks to a target dose of 1000 mg/day. End-points included progression-free survival (PFS)>or=6 months, toxicity, response, PFS and survival. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble endothelial protein C receptor (sEPCR) were evaluated in pre- and post-treatment serum and plasma. RESULTS: Of 30 enrolled patients, one was ineligible (wrong histology). Median age was 56 years. Among 29 eligible patients, seven reached the target dose and only two received more than 4 cycles. Two patients (7%) experienced PFS>or=6 months. There were no objective responses, seven (24%) had stable disease, 19 (66%) progressed and 3 (10%) were not evaluable for response. Median PFS was 1.9 months and median overall survival was 8.3 months. Grade 4 AEs were not observed. The most common grade 3 AEs were neurologic (6), pulmonary (4) and constitutional (3). Treatment with thalidomide was associated with a significant decrease in plasma bFGF (p=0.008) and serum sEPCR (p=0.006), but not in plasma VEGF. Plasma VEGF was associated with increased risk of progression (hazard ratio [HR]=3.5; 95% confidence interval (CI)=1.5-7.8; p=0.003) and death (HR=4.7; 95% CI=1.6-13.8; p=0.005) after adjusting for GOG performance status. CONCLUSIONS: Thalidomide was not active in patients with uterine LMS and did not alter VEGF concentration. The association between pretreatment VEGF and prognosis in this population supports further evaluation of anti-angiogenic therapies in uterine LMS. FAU - McMeekin, D Scott AU - McMeekin DS AD - University of Oklahoma, Department of Gynecologic Oncology, Health Sciences Center, OB/GYN, Oklahoma City, OK 73190, and Department of Reproductive Medicine, University Hospitals of Cleveland, OH 44106, USA. scott-mcmeekin@ouhsc.edu FAU - Sill, Michael W AU - Sill MW FAU - Darcy, Kathleen M AU - Darcy KM FAU - Stearns-Kurosawa, Deborah J AU - Stearns-Kurosawa DJ FAU - Webster, Kenneth AU - Webster K FAU - Waggoner, Steven AU - Waggoner S FAU - Benbrook, Doris AU - Benbrook D LA - eng GR - CA 27469/CA/NCI NIH HHS/United States GR - CA 37517/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural DEP - 20070627 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antigens, CD) RN - 0 (Biomarkers, Tumor) RN - 0 (Endothelial Protein C Receptor) RN - 0 (PROCR protein, human) RN - 0 (Receptors, Cell Surface) RN - 0 (Vascular Endothelial Growth Factor A) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 4Z8R6ORS6L (Thalidomide) SB - IM MH - Adult MH - Aged MH - Angiogenesis Inhibitors/*therapeutic use MH - Antigens, CD/blood MH - Biomarkers, Tumor/blood MH - Dose-Response Relationship, Drug MH - Endothelial Protein C Receptor MH - Female MH - Fibroblast Growth Factor 2/blood MH - Humans MH - Leiomyosarcoma/*blood supply/*drug therapy MH - Middle Aged MH - Neoplasm Recurrence, Local/blood supply/drug therapy MH - Neovascularization, Pathologic/blood/drug therapy MH - Proportional Hazards Models MH - Receptors, Cell Surface/blood MH - Thalidomide/*therapeutic use MH - Uterine Neoplasms/*blood supply/*drug therapy MH - Vascular Endothelial Growth Factor A/blood EDAT- 2007/06/29 09:00 MHDA- 2007/10/12 09:00 CRDT- 2007/06/29 09:00 PHST- 2006/12/21 00:00 [received] PHST- 2007/05/03 00:00 [revised] PHST- 2007/05/14 00:00 [accepted] PHST- 2007/06/29 09:00 [pubmed] PHST- 2007/10/12 09:00 [medline] PHST- 2007/06/29 09:00 [entrez] AID - S0090-8258(07)00353-8 [pii] AID - 10.1016/j.ygyno.2007.05.013 [doi] PST - ppublish SO - Gynecol Oncol. 2007 Sep;106(3):596-603. doi: 10.1016/j.ygyno.2007.05.013. Epub 2007 Jun 27.