Continuous anti-angiogenic therapy after tumor progression in patients with recurrent high-grade epithelial ovarian cancer: phase I trial experience

Oncotarget. 2016 Jun 7;7(23):35132-43. doi: 10.18632/oncotarget.9048.

Abstract

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.

Keywords: anti-angiogenesis; epithelial ovarian cancer; overall survival; progression-free survival; tumor progression.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Ovarian Epithelial
  • Clinical Trials, Phase I as Topic
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Proportional Hazards Models
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents