OBJECTIVE: Potential predictive/prognostic angiogenic markers were prospectively examined in a phase II trial of bevacizumab in epithelial ovarian cancer (EOC)/primary peritoneal cancer (PPC). METHODS:Recurrent/persistent EOC/PPC patients were treated with bevacizumab (15 mg/kg IV q21days) until disease progression. Validated-immunohistochemistry (IHC) assays were performed on pre-cycle 1/4 tumor biopsies for CD31-microvessel density (MVD), VEGF-histoscore (HS), p53-HS, and TSP1 image analysis score (IA). Pre-cycle 1/4 serum and plasma VEGF were quantified using a validated-ELISA. RESULTS:CD31-MVD and serum VEGF, evaluated pre-cycle 1 in 41/61 and 51/61 eligible patients, respectively, did not appear to be correlated. High CD31-MVD, categorized at the median, appeared to be associated with tumor response, a 13-month shorter median survival, and an increased risk of death (unadjusted hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.067-4.467). In addition, each standard deviation (SD) increase in CD31-MVD appeared to be associated with worse survival in unadjusted and adjusted analyses. IHC and plasma biomarkers did not change with bevacizumab treatment except for serum VEGF, which appeared to decrease during bevacizumab treatment. This decrease was not associated with response. High pre-cycle 1 serum VEGF, categorized at the median, was associated with 22-month shorter median survival and an increased risk of death (unadjusted HR = 2.7, 95% CI = 1.369-5.191). Categorized p53 appeared to be associated with unadjusted survival and each SD increase in TSP1-IA appeared to be associated with a decreased risk of progression in unadjusted and adjusted analyses. CONCLUSIONS: Despite the limitations in sample size and exploratory nature of the study, angiogenic markers in tumor and serum may provide prognostic value in recurrent/persistent EOC/PPC, and are being prospectively evaluated in the GOG phase III trial of carboplatin, paclitaxel and bevacizumab/placebo in previously untreated EOC/PPC.
RCT Entities:
OBJECTIVE: Potential predictive/prognostic angiogenic markers were prospectively examined in a phase II trial of bevacizumab in epithelial ovarian cancer (EOC)/primary peritoneal cancer (PPC). METHODS: Recurrent/persistent EOC/PPC patients were treated with bevacizumab (15 mg/kg IV q21days) until disease progression. Validated-immunohistochemistry (IHC) assays were performed on pre-cycle 1/4 tumor biopsies for CD31-microvessel density (MVD), VEGF-histoscore (HS), p53-HS, and TSP1 image analysis score (IA). Pre-cycle 1/4 serum and plasma VEGF were quantified using a validated-ELISA. RESULTS:CD31-MVD and serum VEGF, evaluated pre-cycle 1 in 41/61 and 51/61 eligible patients, respectively, did not appear to be correlated. High CD31-MVD, categorized at the median, appeared to be associated with tumor response, a 13-month shorter median survival, and an increased risk of death (unadjusted hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.067-4.467). In addition, each standard deviation (SD) increase in CD31-MVD appeared to be associated with worse survival in unadjusted and adjusted analyses. IHC and plasma biomarkers did not change with bevacizumab treatment except for serum VEGF, which appeared to decrease during bevacizumab treatment. This decrease was not associated with response. High pre-cycle 1 serum VEGF, categorized at the median, was associated with 22-month shorter median survival and an increased risk of death (unadjusted HR = 2.7, 95% CI = 1.369-5.191). Categorized p53 appeared to be associated with unadjusted survival and each SD increase in TSP1-IA appeared to be associated with a decreased risk of progression in unadjusted and adjusted analyses. CONCLUSIONS: Despite the limitations in sample size and exploratory nature of the study, angiogenic markers in tumor and serum may provide prognostic value in recurrent/persistent EOC/PPC, and are being prospectively evaluated in the GOG phase III trial of carboplatin, paclitaxel and bevacizumab/placebo in previously untreated EOC/PPC.
Authors: Jennifer M Rubatt; Kathleen M Darcy; Alan Hutson; Sarah M Bean; Laura J Havrilesky; Lisa A Grace; Andrew Berchuck; Angeles Alvarez Secord Journal: Gynecol Oncol Date: 2009-01-09 Impact factor: 5.482
Authors: R Mehta; A Kyshtoobayeva; T Kurosaki; E J Small; H Kim; R Stroup; C E McLaren; K T Li; J P Fruehauf Journal: Clin Cancer Res Date: 2001-01 Impact factor: 12.531
Authors: A A Alvarez; J R Axelrod; R S Whitaker; P D Isner; R C Bentley; R K Dodge; G C Rodriguez Journal: Gynecol Oncol Date: 2001-08 Impact factor: 5.482
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; William Cruz-Munoz; Georg A Bjarnason; James G Christensen; Robert S Kerbel Journal: Cancer Cell Date: 2009-03-03 Impact factor: 31.743
Authors: David Bender; Michael W Sill; Heather A Lankes; Henry D Reyes; Christopher J Darus; James E Delmore; Jacob Rotmensch; Heidi J Gray; Robert S Mannel; Jeanne M Schilder; Mark I Hunter; Carolyn K McCourt; Megan I Samuelson; Kimberly K Leslie Journal: Gynecol Oncol Date: 2015-07-15 Impact factor: 5.482
Authors: Dirk O Bauerschlag; Felix Hilpert; Werner Meier; Jörn Rau; Ivo Meinhold-Heerlein; Nicolai Maass; Andreas Dubois; Jalid Sehouli; Norbert Arnold; Christian Schem; Hans-Heinrich Oberg; Klaus Baumann Journal: Transl Oncol Date: 2013-06-01 Impact factor: 4.243
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