title: Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide.
abstract: BACKGROUND
  Thalidomide has potent anti-inflammatory and anti-angiogenic properties. It was evaluated in combination with chemotherapy in two randomised placebo-controlled trials in patients with small cell lung cancer (SCLC, n=724) and advanced non-small cell lung cancer (NSCLC, n=722). Neither study demonstrated an improvement in overall survival with the addition of thalidomide to chemotherapy. This study investigated circulating angiogenic biomarkers in a subset of these patients.
  
  
  METHODS
  Serial plasma samples were collected in a cohort of patients enrolled in these two trials (n=95). Vascular endothelial growth factor (VEGF), soluble truncated form of VEGF receptor-2 (sVEGFR-2), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured by enzyme-linked immunosorbent assays. Results were correlated with patient clinical data including stage, response rate and progression-free survival (PFS).
  
  
  RESULTS
  Baseline biomarker levels were not significantly different between SCLC and NSCLC. For pooled treatment groups, limited stage SCLC was associated with lower baseline VEGF (P=0.046), sICAM-1 (P=0.008) and IL-8 (P=0.070) than extensive stage disease. Low baseline IL-8 was associated with a significantly improved PFS in both SCLC and NSCLC (P=0.028), and a greater reduction in IL-8 was associated with a significantly improved tumour response (P=0.035). Baseline angiogenic factor levels, however, did not predict response to thalidomide.
  
  
  CONCLUSIONS
  Circulating angiogenic biomarkers did not identify patients who benefited from thalidomide treatment.
authors.affiliation: Academic Unit of Clinical Oncology, School of Medicine & Biomedical Sciences, University of Sheffield, Sheffield S10 2RX, UK. r.j.young@sheffield.ac.uk
authors.forename: R J
authors.initials: RJ
authors.lastname: Young
authors.forename: A W
authors.initials: AW
authors.lastname: Tin
authors.forename: N J
authors.initials: NJ
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Jitlal
authors.forename: S M
authors.initials: SM
authors.lastname: Lee
authors.forename: P J
authors.initials: PJ
authors.lastname: Woll
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D017326:Clinical Trials, Phase III as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D055752:Small Cell Lung Carcinoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D016019:Survival Analysis; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000093542:Gemcitabine
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; D016209:Interleukin-8; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1; D013792:Thalidomide; D005047:Etoposide; D016190:Carboplatin; D000093542:Gemcitabine