Table 2a. Anti-VEGF antibodies and circulating biomarkers.
| References | Drug, disease and trial | Biomarkers | N | Drug-induced changes | Prognostic and predictive values |
|---|---|---|---|---|---|
| Dowlati et al (2008) | Carboplatin and Paclitaxel± Bevacizumab NSCLC (E4599); Phase 2/3 | VEGF E-selectin FGF-2 ICAM | 160 | ↓E-selectin ↑FGF-2 | Baseline VEGF predicts response (P=0.01) -Low baseline VEGF: better PFS (P=0.04) -Low ICAM: better OS (P=0.00005),1 year survival and high RR (P=0.02) |
| Siegel et al (2008) | Bevacizumab Unresectable HCC Phase 2 | VEGF SDF-1 HUVEC | 8 | ↓VEGF and SDF-1 ↓HuVEC angiogenic score | ↑VEGF and SDF-1 on progression -VEGF and SDF-1 levels correlate with angiogenic score |
| Yang et al (2003) | Bevacizumab mRCC; Phase 2 | VEGF | 113 | ↑VEGF | NS |
| Nimeiri et al (2008) | Bevacizumab+Erlotinib Recurrent ovarian cancer Phase 2 | sVEGFR-2 Urine VEGF | 11 | NS | NS |
| Ko et al (2008) | Gemcitabine+Cisplatin+Bevacizumab Pancreatic cancer; Phase 2 | VEGF FGF-2 | 46 | ↑VEGF ↑FGF-2 | NS |
| Garcia et al (2008) | Cyclophosphamide+Bevacizumab Ovarian cancer; Phase 2 | VEGF E-selectin TSP-1 | 70 | ↑VEGF and ↓TSP-1 | NS |
| Denduluri et al (2008) | Bevacizumab Breast cancer Pilot study | VEGF sVCAM-1 sVEGFR-2 | 21 | ↑sVCAM-1 ↑sVEGFR-2 | NS |
| Varker et al (2007) | Bevacizumab±IFNα-2b Malignant melanoma Phase 2 | VEGF FGF-2 | 32 | NS | NS |
| Yao et al (2008) | Octreotide+INFα-2b+ Bevacizumab NET; Phase 2 | FGF-2 IL-8 | 36 | ↓FGF-2 ↑ IL-8 | NS |
| Jayson et al (2005) | HuMV833 Advanced cancer Phase 1 | VEGFR-1, IL-8, sVCAM-1, FGF-2, E-selectin, HGF | 20 | ↑VEGF ↓FGF, HGF | NS |
| Dellapasqua et al (2008) | Cyclophosphamide+Capecitabine+ Bevacizumab Breast cancer; Phase 2 | CEC CEPC | 46 | ↓CEC | High baseline CECs correlate with OR (P=0.02), clinical benefit (P=0.01) and improved PFS (P=0.04) |
| Willett et al (2005) | Chemoradiotherapy+Bevacizumab Rectal cancer; Phase 1 | CEC CEPC | 6 | ↓CEC/CEPC | NS |
Abbreviations: VEGF=vascular endothelial growth factor; CEC=circulating endothelial cell; CEPC=circulating endothelial progenitor cell; FGF-2=fibroblast growth factor-2; HCC=hepatocellular carcinoma; HGF=hepatocyte growth factor; HUVEC=human umbilical vein endothelial cell; ICAM=intercellular adhesion molecule; INFα-2b=interferon α-2b; mRCC=metastatic renal cell carcinoma; NET=neuroendocrine tumour; NS=not significant; NSCLC=non-small-cell lung cancer; OR=overall response; OS=overall survival; RR=response rate; SDF-1=stromal cell-derived factor-1; sVCAM=soluble vascular cell adhesion molecule; sVEGFR-2=soluble VEGF receptor 2; TSP-1=thrombospondin-1.