Table 3b. VEGFR, TKi and imaging biomarkers.
| References | Drug and trial | DCE-MRI biomarkers | N | Drug-induced changes | Prognostic/predictive value |
|---|---|---|---|---|---|
| Flaherty et al (2008) | Sorafenib Renal cancer; Phase 2 | Ktrans | 17 | ↓Ktrans | High baseline (P=0.02) and % change in Ktrans (P=0.01) predict PFS |
| Hahn et al (2008) | Sorafenib Renal Cancer; Phase 2 | IAUC, vp, Ktrans | 56 | ↓IAUC, vp, Ktrans | High baseline Ktrans: better PFS (P=0.027) |
| Batchelor et al (2007) | Cediranib (AZD2171) Glioblastoma; Phase 2 | Ktrans, ve, vessel size | 16 | ↓Ktrans ↓vessel size | NS |
| Drevs et al (2007) | Cediranib (AZD2171) Advanced cancer; Phase 1 | IAUC | 24 | ↓IAUC | NS |
| Miller et al (2005) | Vandetanib (AZD6474) Breast cancer; Phase 2 | IAUC, Ktrans | 11 | ↓IAUC Ktrans | NS |
| Rosen et al (2007) | AMG706 Advanced Cancer; Phase 1 | IAUC | 18 | ↓IAUC | NS |
| Jonker et al (2007) | Brivanib (BMS-582664) Advanced cancer; Phase 1 | IAUC, Ktrans | 50 | ↓Ktrans, ↓IAUC | NS |
| Padhani et al (2006) | BIBF1120 Advanced cancer; Phase 1 | IAUC, Ktrans, Kep | 35 | No consistent effect | NS |
| Mross et al (2005b) | BIBF1120 Advanced Cancer; Phase 1 | IAUC, Ki | 27 | ↓IAUC, Ki | NS |
| Liu et al (2005) | Axitinib (AG013736) Advanced cancer; Phase 1 | IAUC, Ktrans | 17 | ↓IAUC, Ktrans | NS |
| Mross et al (2005) | Vatalanib (PTK/ZK) Colorectal/breast ca Phase 1 | Ki | 27 | ↓Ki | Change in Ki: RR and progression |
| Thomas et al (2005) | Vatalanib (PTK/ZK) Advanced cancer; Phase 1 | Ki | 43 | ↓Ki | Change in Ki: predicts progression |
| Conrad et al (2004) | Vatalanib (PTK/ZK) Glioblastoma; Phase 1/2 | Ki, RBV | 14 | ↓Ki | Change in Ki predicts progression |
| Morgan et al (2003) | Vatalanib (PTK/ZK) Colorectal cancer; Phase 1 | Ki | 26 | ↓Ki | Change in Ki predicts RR and progression |
| O’Donnell et al (2005) | Semaxinib (SU5416) Advanced Cancer; Phase 1 | Ktrans | 24 | NS | NS |
| Dowlati et al (2005) | Semaxinib (SU5416) Advanced cancer; Phase 1 | Kep | 11 | NS | NS |
| Medved et al (2004) | Semaxinib (SU5416) | IAUC | 19 | ↓IAUC | NS |
| Xiong et al (2004) | SU6668 Advanced cancer; Phase 1 | IAUC, gradient | 27 | NS | NS |
Abbreviations: VEGF=vascular endothelial growth factor; DCE-MRI=dynamic contrast-enhanced magnetic resonance imaging; IAUC=initial area under the contrast agent concentration – time curve; Ki=unidirectional influx constant; kep=rate constant; ktrans=bi-directional transfer coefficient; NS=not significant; rBV=regional blood volume; RR=response rate; ve=volume of the extravascular extracellular space; vp=blood plasma volume.