Continuous anti-angiogenic therapy after tumor progression in patients with recurrent high-grade epithelial ovarian cancer: phase I trial experience
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Ming-Mo Hou1,3,*, Zhijie Wang4,*, Filip Janku1, Sarina Piha-Paul1, Aung Naing1, David Hong1, Shannon Westin2, Robert L. Coleman2, Anil K. Sood2, Apostolia M. Tsimberidou1, Vivek Subbiah1, Jennifer Wheler1, Ralph Zinner1, Karen Lu2, Funda Meric-Bernstam1, Siqing Fu1
1Departments of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
2Departments of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
3Division of Hematology-Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
4Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Beijing Institute for Cancer Research, Beijing, China
*These authors have contributed equally to this work
Siqing Fu, e-mail: [email protected]
Keywords: epithelial ovarian cancer, anti-angiogenesis, tumor progression, progression-free survival, overall survival
Received: March 01, 2016 Accepted: April 10, 2016 Published: April 27, 2016
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 bevacizumab-based 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.
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