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Anti-angiogenic agents: clinical trial design and therapies in development
1University of Oxford, ICRF Medical Oncology Unit, The Churchill, Old Road, OX3 7LJ, Oxford, UK.
Abstract:
Development of therapies aimed at inhibiting the growth of new blood vessels is among the most intensively studied approaches to the treatment of cancer. Deciphering the many biological processes involved in tumour angiogenesis has led to the development of new agents targeting either metalloproteases, angiogenic growth factors, endothelial cells or other components of the tumour neovasculature. More than 35 anti-angiogenic agents have already entered clinical trials in cancer patients and most of them are reviewed here. It has rapidly emerged from the preliminary results of these studies that the steps and endpoints classically adopted and used worldwide in developing new anticancer agents could be inappropriate to assess the efficacy of agents that do not target cancer cells directly. One of the major challenges for scientists and clinical researchers is to define new surrogate endpoints adapted to anti-angiogenic agents in the design of clinical trials. Once this has been achieved, the place of clinically active anti-angiogenic agents will need to be further refined in order to determine where they best fit in our current armamentarium, either as single agents or in combination with classical anticancer therapies. Finally, the use of these new agents may in the future encompass every aspect of cancer management, not only from palliative to curative treatment but also in the prevention of cancer.
Insights
Developing anti-angiogenic therapies, which inhibit tumor blood vessel growth, is crucial for cancer treatment. New clinical trial endpoints are needed to accurately assess these novel agents
Area of Science:
- Oncology
- Vascular Biology
- Drug Development
Background:
- Cancer treatment increasingly focuses on inhibiting tumor angiogenesis, the formation of new blood vessels.
- Numerous anti-angiogenic agents targeting various aspects of tumor neovasculature have been developed.
Purpose of the Study:
- To review existing anti-angiogenic agents in clinical trials.
- To address the challenge of defining appropriate endpoints for evaluating anti-angiogenic therapies.
- To discuss the future role of anti-angiogenic agents in comprehensive cancer management.
Main Methods:
- Review of over 35 anti-angiogenic agents in clinical trials.
- Analysis of challenges in assessing efficacy of non-directly cytotoxic anticancer agents.
- Discussion on the need for novel surrogate endpoints in clinical trial design.
Main Results:
- More than 35 anti-angiogenic agents are currently in clinical trials.
- Traditional cancer agent evaluation methods may be unsuitable for anti-angiogenic therapies.
- Defining new surrogate endpoints is a critical challenge for clinical research.
Conclusions:
- Anti-angiogenic agents represent a significant advancement in cancer therapy.
- The development of adapted clinical trial endpoints is essential for accurate efficacy assessment.
- These agents hold potential for use across the entire spectrum of cancer care, including prevention.