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Angiogenesis modifications related with cetuximab plus irinotecan as anticancer treatment in advanced colorectal
B Vincenzi1, D Santini, A Russo
1Medical Oncology, University Campus Bio-Medico, Rome, Italy.
Introduction:
Angiogenesis has been correlated with increased invasion and metastases in a variety of human neoplasms. Inadequate inhibition of the growth of tumor microvessels by anticancer agents may result in treatment failure, rated clinically as progressive or stable disease. We designed this trial to investigate the modification of the vascular endothelial growth factor (VEGF) and interferon-gamma (IFN-gamma) in advanced colorectal cancer patients during treatment with a weekly combination of cetuximab plus irinotecan.
Materials And Methods:
Forty-five metastatic colorectal cancer patients were prospectively evaluated for circulating levels of VEGF and IFN-gamma during the treatment with cetuximab (initial dose of 400 mg/m(2), followed by weekly infusions of 250 mg/m(2)) plus weekly irinotecan (90 mg/m(2)). The circulating levels of the cytokines were assessed at the following time points: just before and at 1, 21, 50 and 92 days after the start of cetuximab plus irinotecan treatment.
Results:
Basal serum VEGF median levels were significantly decreased just at the first day (after the first treatment infusion (P = 0.016). The VEGF persisted at the following time points reaching the highest statistical significance 92 days after the first infusion (P < 0.0001). On the contrary, IFN-gamma values showed a statistical significant increase one day after the first infusion (P < 0.0001). This effect persisted 21 days after the treatment start (P = 0.001), but was no more evident at the following time points. Moreover, a linear regression model with variance analysis showed a significant negative correlation between VEGF and IFN-gamma values 1, 21 and 50 days after the treatment beginning (P = 0.002, 0.001 and 0.047, respectively).
Conclusions:
This study suggests that a cetuximab may induce a modulation of VEGF circulating levels. The reduction of VEGF serum levels is a sudden and long lasting phenomenon. Moreover, in our study we identified a IFN-gamma increase, even if the specific role of this behavior remains to be investigated.
Insights
This study shows that cetuximab plus irinotecan treatment significantly reduces vascular endothelial growth factor (VEGF) in advanced colorectal cancer patients. Interferon-gamma (IFN-gamma) levels transiently increased, suggesting a complex immune response to the therapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Angiogenesis is crucial for tumor growth, invasion, and metastasis in human neoplasms.
- Inadequate inhibition of tumor microvessel growth by anticancer agents can lead to treatment failure.
- This study investigates the impact of cetuximab plus irinotecan on VEGF and IFN-gamma in advanced colorectal cancer.
Purpose of the Study:
- To investigate the modulation of vascular endothelial growth factor (VEGF) and interferon-gamma (IFN-gamma) levels.
- To assess these changes in patients with advanced colorectal cancer receiving cetuximab plus irinotecan.
- To determine the temporal dynamics of these cytokine alterations during treatment.
Main Methods:
- Prospective evaluation of 45 metastatic colorectal cancer patients.
- Measurement of circulating VEGF and IFN-gamma levels before and at multiple time points after treatment initiation.
- Treatment regimen: weekly cetuximab plus irinotecan.
Main Results:
- Significant decrease in serum VEGF levels observed as early as day 1 post-treatment, persisting up to day 92.
- Significant transient increase in IFN-gamma levels observed at day 1 and day 21 post-treatment.
- Significant negative correlation found between VEGF and IFN-gamma levels at multiple time points.
Conclusions:
- Cetuximab treatment induces significant and sustained reduction in circulating VEGF levels.
- A transient increase in IFN-gamma was observed, though its specific role requires further investigation.
- The findings suggest a potential mechanism for cetuximab's efficacy in colorectal cancer through VEGF modulation.
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