The predictive role of serum VEGF in an advanced malignant mesothelioma patient cohort treated with thalidomide alone or combined with cisplatin/gemcitabine

Lung Cancer. 2012 Feb;75(2):248-54. doi: 10.1016/j.lungcan.2011.06.007. Epub 2011 Jul 16.

Abstract

There is a need for new treatment strategies and prognostic markers for the management of malignant mesothelioma (MM). The activity of thalidomide/cisplatin/gemcitabine (arm A) or thalidomide alone (arm B) was investigated in two parallel phase II studies in patients with advanced MM, using 6 month progression free survival (PFS) as the principal end-point. The predictive role of pre-treatment and 8 week follow-up serum C-reactive protein (CRP), interlukin-6 (IL-6), interlukin-6 soluble receptor (sIL-6R), mesothelin (SMRP) and vascular endothelial growth factor (VEGF) was also assessed. The proportion of patients with stable disease for >6 months was similar in both studies (arm A 35%, arm B 29%) and toxicity was mainly grade I/II. In univariate analyses only pre-treatment VEGF and CRP were correlated with survival. At 8 weeks post treatment, increased survival was found with low (<median) VEGF and CRP compared with high (>median) VEGF and CRP (P<0.05). Change in VEGF over the first 8 weeks of treatment was also predictive for survival (P<0.05). When pre-treatment VEGF was >median, decreasing VEGF was associated with increased survival (P<0.05). In conclusion, thalidomide alone, or in combination with cisplatin/gemcitabine, controlled disease for >6 months in ∼30% of patients. Patients with decreasing VEGF during treatment had longest survival. Pre-treatment VEGF or CRP and early change in VEGF on treatment may predict treatment benefit and should be examined in future studies.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • C-Reactive Protein / analysis
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Clinical Trials, Phase II as Topic
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Female
  • Humans
  • Male
  • Mesothelioma / blood
  • Mesothelioma / drug therapy*
  • Mesothelioma / mortality
  • Middle Aged
  • Thalidomide / adverse effects
  • Thalidomide / therapeutic use*
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Vascular Endothelial Growth Factor A
  • Deoxycytidine
  • Thalidomide
  • C-Reactive Protein
  • gemcitabine
  • Cisplatin