Predictive and prognostic angiogenic markers in a gynecologic oncology group phase II trial of bevacizumab in recurrent and persistent ovarian or peritoneal cancer.
Predictive and prognostic angiogenic markers in a gynecologic oncology group phase II trial of bevacizumab in recurrent and persistent ovarian or peritoneal cancer.
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DOI：
10.1016/j.ygyno.2010.08.016
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发表时间：
2010-12
影响因子：
4.7
通讯作者：
Fruehauf JP
中科院分区：
文献类型：
--
作者：
Han ES;Burger RA;Darcy KM;Sill MW;Randall LM;Chase D;Parmakhtiar B;Monk BJ;Greer BE;Connelly P;Degeest K;Fruehauf JP
在贝伐单抗治疗上皮性卵巢癌(EOC)/原发性腹膜癌(PPC)的II期试验中，前瞻性地检测了潜在的预测/预后血管生成标记物。复发/持续性EOC/PPC患者接受贝伐单抗(15 mg/kg静脉滴注，q21天)治疗，直至病情进展。对周期前1/4的肿瘤组织进行CD31微血管密度(MVD)、血管内皮生长因子组织核心(HS)、P53-HS和TSP1图像分析评分(IA)的验证免疫组织化学(IHC)检测。用双抗体夹心法测定前1/4周期血清和血浆中血管内皮生长因子的含量。在第一周期前分别评估41/61和51/61符合条件的患者的CD31-MVD和血清血管内皮生长因子，似乎没有相关性。高CD31微血管密度(按中位数分类)似乎与肿瘤反应、13个月的中位生存期缩短和死亡风险增加(未调整的危险比[HR]=2.295%可信区间[CI]=1.067-4.467)相关。此外，在未经调整和调整的分析中，CD31-MVD的每一次标准差(SD)增加似乎与较差的存活率相关。贝伐单抗治疗后IHC和血浆生物标记物没有改变，但血清血管内皮生长因子在贝伐单抗治疗期间似乎有所下降。这一下降与反应无关。第1周期前高水平的血清血管内皮生长因子水平处于中位数，与22个月的中位生存期缩短和死亡风险增加相关(未调整的HR=2.795%CI=1.369-5.191)。在未经调整和调整的分析中，分类的P53似乎与未调整的生存期相关，TSP1-IA的每一次SD增加似乎与进展风险的降低相关。尽管这项研究的样本量和探索性有限，但肿瘤和血清中的血管生成标记物可能在复发/持续性EOC/PPC中提供预后价值，并正在卡铂、紫杉醇和贝伐单抗/安慰剂的GOG III期试验中进行前瞻性评估，用于先前未经治疗的EOC/PPC。
Potential predictive/prognostic angiogenic markers were prospectively examined in a phase II trial of bevacizumab in epithelial ovarian cancer (EOC)/primary peritoneal cancer (PPC). Recurrent/persistent EOC/PPC patients were treated with bevacizumab (15mg/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. 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. 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.
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