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Vascular density analysis in colorectal cancer patients treated with vatalanib (PTK787/ZK222584) in the randomised
A Giatromanolaki1, M I Koukourakis, E Sivridis
1Departments of Pathology, and Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis 68100, Greece.
Background:
Pharmacological inhibitors of vascular endothelial growth factor (VEGF) receptors, like vatalanib, have been tested in randomised trials (CONFIRM (Colorectal Oral Novel therapy For the Inhibition of Angiogenesis and Retarding of Metastases) 1 and 2) in colorectal cancer showing activity in a subgroup of patients with high serum LDH expression. In the current study, we assessed the predictive role of vascular density (VD) in patients treated in the above trials.
Methods:
Paraffin-embedded materials from 141 patients were analysed with immunohistochemistry for the expression of the CD31 (pan-endothelial cell marker) and of phosphorylated pVEGFR2/KDR on endothelial cells. The VD was correlated with response to therapy and with progression-free (PFS) and overall survival (OS).
Results:
A significant association of pVEGFR2/KDR+ VD with poor response in the placebo group was noted (response rates (RRs) 15% (3/20) when high VD vs 52% (26/50) when low VD; P=0.006). The RR increased from 15 (3/20) to 50% (11/22) in tumours with high VD when vatalanib was added to chemotherapy (P=0.02). A significantly improved PFS was noted in patients with high pVEGFR2/KDR+ VD when treated with vatalanib (P=0.002). A similar effect was also noted in patients with high CD31+ VD (P=0.07). Overall survival was marginally improved (P=0.07).
Conclusion:
Assessment of the activated vessel density may allow the stratification of patients recruited in randomised trials with VEGFR-targeting anti-angiogenic agents, unmasking their therapeutic potential and enabling their introduction in the clinical practice for the benefit of specific patient subgroups, at the same time reducing the cost of therapy.
Insights
Vascular density (VD) predicts response to anti-angiogenic therapy in colorectal cancer. Activated vessel density may help identify patients who benefit from vascular endothelial growth factor receptor (VEGFR) inhibitors.
Area of Science:
- Oncology
- Translational Research
- Cancer Biomarkers
Background:
- Vascular endothelial growth factor (VEGF) receptor inhibitors like vatalanib show activity in colorectal cancer subgroups.
- Previous trials indicated a link between high serum LDH and response to anti-angiogenic therapy.
- This study investigates vascular density (VD) as a predictive biomarker.
Purpose of the Study:
- To assess the predictive role of vascular density (VD) in colorectal cancer patients treated with anti-angiogenic agents.
- To correlate vascular density with treatment response, progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Immunohistochemistry was used to analyze CD31 and phosphorylated VEGFR2 (pVEGFR2/KDR) expression in 141 colorectal cancer patients.
- Vascular density was quantified using CD31 and pVEGFR2/KDR staining.
- Correlation analysis was performed between VD and clinical outcomes.
Main Results:
- High pVEGFR2/KDR+ VD was associated with poor response in the placebo group (15% vs 52%).
- Vatalanib treatment increased response rates in patients with high VD (15% to 50%).
- Significantly improved PFS was observed in patients with high pVEGFR2/KDR+ VD treated with vatalanib (P=0.002).
- High CD31+ VD showed a similar trend for improved PFS (P=0.07).
Conclusions:
- Activated vessel density, particularly pVEGFR2/KDR+ VD, can stratify patients for VEGFR-targeting anti-angiogenic therapies.
- This biomarker assessment may reveal therapeutic potential in specific patient subgroups.
- Stratification can optimize treatment selection and reduce healthcare costs.
