Rapid decrease in serum VEGF-A levels may be a worse prognostic biomarker for patients with platinum-resistant recurrent ovarian cancer treated with bevacizumab and gemcitabine

Cancer Chemother Pharmacol. 2020 May;85(5):941-947. doi: 10.1007/s00280-020-04070-8. Epub 2020 Apr 11.

Abstract

Purpose: The aim of this study was to investigate the association between changes in the levels of vascular endothelial growth factors (VEGFs) after treatment with bevacizumab and gemcitabine (Bev-Gem) and the clinical outcome.

Methods: Platinum-resistant ovarian cancer patients treated with Bev-Gem therapy at our hospital between 2014 and 2018 were identified. Serum VEGF levels at the first and second treatment cycle were measured by ELISA. All patients were categorized into two groups-patients with > 50% decrease in serum VEGF-A levels (Group A) and patients with < 50% decrease serum VEGF-A levels (Group B). The association between clinical outcome and serum VEGF levels was investigated between the two groups.

Results: Among 18 patients, 10 were in Group A and 8 in Group B. Group A exhibited a lower response rate (0% vs.75% p < 0.01) and clinical benefit rate (60% vs.100% p = 0.02) than Group B. The median serum VEGF-A level of Group A before the first cycle of Bev-Gem therapy was higher than that in Group B (61.2 vs. 3.7 pg/mL, p < 0.01). Group A exhibited worse PFS (7 vs., 10 months, p < 0.01) and OS (17 vs. 26 months, p = 0.04) than Group B. There were more patients with > 10% increase in serum VEGF-B levels in Group A than in Group B (p < 0.01).

Conclusion: The rapid decrease in VEGF-A levels and the resultant increase in serum VEGF-B levels might be associated with an unfavorable clinical outcome. Large-scale studies are needed to further examine these results.

Keywords: Bevacizumab; Gemcitabine; Platinum-resistant recurrence; Vascular endothelial growth factor.

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / adverse effects
  • Bevacizumab* / pharmacokinetics
  • Biomarkers, Pharmacological / blood
  • Biomarkers, Tumor / blood
  • Cisplatin / pharmacology*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Disease Progression
  • Drug Monitoring / methods
  • Female
  • Gemcitabine
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local* / blood
  • Neoplasm Recurrence, Local* / drug therapy
  • Neoplasm Recurrence, Local* / pathology
  • Neoplasm Staging
  • Ovarian Neoplasms* / blood
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / pathology
  • Predictive Value of Tests
  • Prognosis
  • Vascular Endothelial Growth Factor A / blood*
  • Vascular Endothelial Growth Factor B / blood*

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor B
  • Deoxycytidine
  • Bevacizumab
  • Cisplatin
  • Gemcitabine