OBJECTIVE: To explore the safety, efficacy, and biomarkers of bevacizumab with gemcitabine and oxaliplatin in women with recurrent platinum-sensitive ovarian carcinoma. METHODS: The patients received bevacizumab (10 mg/kg), gemcitabine (1000 mg/m(2)), and oxaliplatin (65 mg/m(2)) on days 1 and 15 in 28-day cycles. The patients with safely accessible tumor underwent intratumoral fluid pressure (IFP) measurements and positron-emission tomographies immediately and 2 weeks after treatment. Blood biomarkers were evaluated at 5 time points. RESULTS: The trial was closed after enrolling 19 of the 53 projected patient accrual. Thirteen (68.5%) of 19 patients showed a response (1 complete response, 12 partial responses), and 6 patients showed stable disease (31.6%). Median progressive-free survival was 36.9 weeks (258.3 days), and the median overall survival was 112.3 weeks (633 days, not reached). Toxicity was acceptable, and there were no arterial thromboses, serious bleeding, gastrointestinal perforations, or complications from the invasive procedures. Bevacizumab with chemotherapy induced a substantial drop in tumor IFP after treatment. The regimen induced sustained elevation in circulating plasma vascular endothelial growth factor (VEGF), placental growth factor (PlGF), basic fibroblast growth factor (bFGF), soluable vascular endothelial growth factor receptor 2 (sVEGFR2), and circulating progenitor cells. Plasma PlGF, VEGFR2(+) monocytes, and urinary matrix metalloproteinase 2 activity showed differential associations with treatment outcome when evaluated at baseline and after 14 days of treatment. CONCLUSIONS: Despite early termination of the study, the results indicate that the regimen was well tolerated and demonstrated activity in platinum-sensitive ovarian cancer. Biomarker evaluations showed that bevacizumab with chemotherapy significantly changed the levels of several circulating cellular and molecular biomarkers. The increases in plasma PlGF and VEGFR2(+) monocytes showed correlations with outcome. These exploratory data should be further evaluated in future studies of bevacizumab in ovarian cancer.
OBJECTIVE: To explore the safety, efficacy, and biomarkers of bevacizumab with gemcitabine and oxaliplatin in women with recurrent platinum-sensitive ovarian carcinoma. METHODS: The patients received bevacizumab (10 mg/kg), gemcitabine (1000 mg/m(2)), and oxaliplatin (65 mg/m(2)) on days 1 and 15 in 28-day cycles. The patients with safely accessible tumor underwent intratumoral fluid pressure (IFP) measurements and positron-emission tomographies immediately and 2 weeks after treatment. Blood biomarkers were evaluated at 5 time points. RESULTS: The trial was closed after enrolling 19 of the 53 projected patient accrual. Thirteen (68.5%) of 19 patients showed a response (1 complete response, 12 partial responses), and 6 patients showed stable disease (31.6%). Median progressive-free survival was 36.9 weeks (258.3 days), and the median overall survival was 112.3 weeks (633 days, not reached). Toxicity was acceptable, and there were no arterial thromboses, serious bleeding, gastrointestinal perforations, or complications from the invasive procedures. Bevacizumab with chemotherapy induced a substantial drop in tumor IFP after treatment. The regimen induced sustained elevation in circulating plasma vascular endothelial growth factor (VEGF), placental growth factor (PlGF), basic fibroblast growth factor (bFGF), soluable vascular endothelial growth factor receptor 2 (sVEGFR2), and circulating progenitor cells. Plasma PlGF, VEGFR2(+) monocytes, and urinary matrix metalloproteinase 2 activity showed differential associations with treatment outcome when evaluated at baseline and after 14 days of treatment. CONCLUSIONS: Despite early termination of the study, the results indicate that the regimen was well tolerated and demonstrated activity in platinum-sensitive ovarian cancer. Biomarker evaluations showed that bevacizumab with chemotherapy significantly changed the levels of several circulating cellular and molecular biomarkers. The increases in plasma PlGF and VEGFR2(+) monocytes showed correlations with outcome. These exploratory data should be further evaluated in future studies of bevacizumab in ovarian cancer.
Authors: Brian C Cooper; Justine M Ritchie; Carrie L W Broghammer; Jeremy Coffin; Joel I Sorosky; Richard E Buller; Mary J C Hendrix; Anil K Sood Journal: Clin Cancer Res Date: 2002-10 Impact factor: 12.531
Authors: Agustin A Garcia; Hal Hirte; Gini Fleming; Dongyun Yang; Denice D Tsao-Wei; Lynda Roman; Susan Groshen; Steve Swenson; Frank Markland; David Gandara; Sidney Scudder; Robert Morgan; Helen Chen; Heinz-Josef Lenz; Amit M Oza Journal: J Clin Oncol Date: 2008-01-01 Impact factor: 44.544
Authors: Robert A Burger; Michael W Sill; Bradley J Monk; Benjamin E Greer; Joel I Sorosky Journal: J Clin Oncol Date: 2007-11-20 Impact factor: 44.544
Authors: John M L Ebos; Christina R Lee; James G Christensen; Anthony J Mutsaers; Robert S Kerbel Journal: Proc Natl Acad Sci U S A Date: 2007-10-17 Impact factor: 11.205
Authors: Rakesh K Jain; Dan G Duda; Christopher G Willett; Dushyant V Sahani; Andrew X Zhu; Jay S Loeffler; Tracy T Batchelor; A Gregory Sorensen Journal: Nat Rev Clin Oncol Date: 2009-06 Impact factor: 66.675
Authors: Christopher G Willett; Yves Boucher; Emmanuelle di Tomaso; Dan G Duda; Lance L Munn; Ricky T Tong; Daniel C Chung; Dushyant V Sahani; Sanjeeva P Kalva; Sergey V Kozin; Mari Mino; Kenneth S Cohen; David T Scadden; Alan C Hartford; Alan J Fischman; Jeffrey W Clark; David P Ryan; Andrew X Zhu; Lawrence S Blaszkowsky; Helen X Chen; Paul C Shellito; Gregory Y Lauwers; Rakesh K Jain Journal: Nat Med Date: 2004-01-25 Impact factor: 53.440
Authors: John M L Ebos; Christina R Lee; William Cruz-Munoz; Georg A Bjarnason; James G Christensen; Robert S Kerbel Journal: Cancer Cell Date: 2009-03-03 Impact factor: 31.743
Authors: Chandrajit P Raut; Yves Boucher; Dan G Duda; Jeffrey A Morgan; Richard Quek; Marek Ancukiewicz; Johanna Lahdenranta; J Paul Eder; George D Demetri; Rakesh K Jain Journal: PLoS One Date: 2012-02-07 Impact factor: 3.240
Authors: Fiona Collinson; Michelle Hutchinson; Rachel A Craven; David A Cairns; Alexandre Zougman; Tobias C Wind; Narinder Gahir; Michael P Messenger; Sharon Jackson; Douglas Thompson; Cybil Adusei; Jonathan A Ledermann; Geoffrey Hall; Gordon C Jayson; Peter J Selby; Rosamonde E Banks Journal: Clin Cancer Res Date: 2013-08-09 Impact factor: 12.531