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Toxicities of antiangiogenic therapy in non-small-cell lung cancer
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. rherbst@mdanderson.or
Abstract:
The addition of antiangiogenic agents has improved overall survival in a wide variety of tumor types, including non-small-cell lung cancer (NSCLC). Antibodies to the vascular endothelial growth factor (VEGF) were the first targeted agent to yield a significant improvement in overall survival when combined with first-line chemotherapy for metastatic NSCLC. Anti-VEGF antibodies and tyrosine kinase inhibitors blocking VEGF receptor (VEGFR) activity are also being investigated in pretreated NSCLC. Initial experience with anti-VEGF antibodies suggested a mild adverse event profile. However, it has become clear with additional experience that antiangiogenic agents are associated with a distinct array of toxicities, such as hemorrhage, hypertension, thromboembolic events, and proteinuria. Furthermore, an increase in chemotherapy-associated toxicities such as neutropenia has been observed with the addition of anti-VEGF antibodies. Multitargeted small-molecule inhibitors that block activity of the VEGFR tyrosine kinase are associated with fatigue and other toxicities in addition to the aforementioned class-effect toxicities, possibly because of their inhibition of multiple signaling pathways. Currently, only patients without predominant squamous cell histology are eligible to receive bevacizumab. Trials are ongoing to address the feasibility of bevacizumab in patients who were excluded from the phase III pivotal trial. Additionally, further investigation is necessary to determine risk factors for hemorrhage with antiangiogenic agents.
Insights
Antiangiogenic agents, like anti-VEGF antibodies, improve survival in non-small-cell lung cancer (NSCLC) but carry risks. Careful patient selection and further research are needed to manage toxicities and identify hemorrhage risk factors.
Area of Science:
- Oncology
- Medical Research
Background:
- Antiangiogenic agents targeting vascular endothelial growth factor (VEGF) have improved survival in various cancers, including non-small-cell lung cancer (NSCLC).
- Initial studies suggested a favorable safety profile for anti-VEGF antibodies, but further experience revealed distinct toxicities.
Purpose of the Study:
- To review the efficacy and toxicity of antiangiogenic agents in NSCLC treatment.
- To highlight the distinct adverse events associated with these agents and their combination with chemotherapy.
- To discuss current limitations and future research directions for antiangiogenic therapy in NSCLC.
Main Methods:
- Review of clinical trial data and accumulated clinical experience with antiangiogenic agents in NSCLC.
- Analysis of adverse event profiles, including hemorrhage, hypertension, thromboembolic events, proteinuria, and chemotherapy-associated toxicities.
- Discussion of ongoing trials and the need for further investigation into risk factors.
Main Results:
- Anti-VEGF antibodies and VEGF receptor (VEGFR) inhibitors have shown survival benefits in metastatic and pretreated NSCLC.
- Significant toxicities associated with antiangiogenic agents include hemorrhage, hypertension, thromboembolic events, and proteinuria.
- Combination therapy with anti-VEGF antibodies can increase chemotherapy-related toxicities like neutropenia.
- Multitargeted inhibitors may cause additional toxicities due to broader pathway inhibition.
Conclusions:
- Antiangiogenic agents offer survival advantages in NSCLC but require careful management of associated toxicities.
- Current eligibility for bevacizumab is limited to patients without predominant squamous cell histology.
- Further research is essential to optimize the use of antiangiogenic agents, including identifying patients at high risk for hemorrhage.
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