TY - JOUR
T1 - Continuous anti-angiogenic therapy after tumor progression in patients with recurrent high-grade epithelial ovarian cancer
T2 - Phase I trial experience
AU - Hou, Ming Mo
AU - Wang, Zhijie
AU - Janku, Filip
AU - Piha-Paul, Sarina
AU - Naing, Aung
AU - Hong, David
AU - Westin, Shannon
AU - Coleman, Robert L.
AU - Sood, Anil K.
AU - Tsimberidou, Apostolia M.
AU - Subbiah, Vivek
AU - Wheler, Jennifer
AU - Zinner, Ralph
AU - Lu, Karen
AU - Meric-Bernstam, Funda
AU - Fu, Siqing
PY - 2016/6/7
Y1 - 2016/6/7
N2 - High-grade epithelial ovarian cancer (HG-EOC) is the most lethal gynecologic malignancy worldwide Once patients develop chemoresistance, effective novel strategies are required to improve prognosis We analyzed characteristics and outcomes of 242 consecutive patients with HG-EOC participating in 94 phase I clinical trials at The University of Texas MD Anderson Cancer Center. Baseline lactate dehydrogenase levels, albumin levels, and number of metastatic sites were independent predictors of overall survival (OS). Receiving more than 1 phase I protocol was associated with improved OS (p < 0.001). Regimens including a chemotherapeutic agent plus bevacizumab or Aurora A kinase inhibitor led to a median progression-free survival (PFS) duration of more than 6 months. Although patients receiving bevacizumabbased regimens in the phase I clinical trials had significantly longer PFS than those receiving other anti-angiogenic therapies (p = 0.017), patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) had significantly longer OS (12.2 months) than those not treated with VEGFR-TKIs (8.6 months, p = 0.015). In conclusion, anti-angiogenic therapy is one of the most important strategies for the treatment of HG-EOC, even in those who have already experienced tumor progression. Therefore, eligible patients with HG-EOC should be encouraged to participate in novel phase I studies of anti-angiogenic therapies, even after disease progression.
AB - High-grade epithelial ovarian cancer (HG-EOC) is the most lethal gynecologic malignancy worldwide Once patients develop chemoresistance, effective novel strategies are required to improve prognosis We analyzed characteristics and outcomes of 242 consecutive patients with HG-EOC participating in 94 phase I clinical trials at The University of Texas MD Anderson Cancer Center. Baseline lactate dehydrogenase levels, albumin levels, and number of metastatic sites were independent predictors of overall survival (OS). Receiving more than 1 phase I protocol was associated with improved OS (p < 0.001). Regimens including a chemotherapeutic agent plus bevacizumab or Aurora A kinase inhibitor led to a median progression-free survival (PFS) duration of more than 6 months. Although patients receiving bevacizumabbased regimens in the phase I clinical trials had significantly longer PFS than those receiving other anti-angiogenic therapies (p = 0.017), patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) had significantly longer OS (12.2 months) than those not treated with VEGFR-TKIs (8.6 months, p = 0.015). In conclusion, anti-angiogenic therapy is one of the most important strategies for the treatment of HG-EOC, even in those who have already experienced tumor progression. Therefore, eligible patients with HG-EOC should be encouraged to participate in novel phase I studies of anti-angiogenic therapies, even after disease progression.
KW - Anti-angiogenesis
KW - Epithelial ovarian cancer
KW - Overall survival
KW - Progression-free survival
KW - Tumor progression
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U2 - 10.18632/oncotarget.9048
DO - 10.18632/oncotarget.9048
M3 - Article
C2 - 27147567
AN - SCOPUS:84973620769
SN - 1949-2553
VL - 7
SP - 35132
EP - 35143
JO - Oncotarget
JF - Oncotarget
IS - 23
ER -