MEETING REPORT Angiogenesis antagonists: current clinical trials Steven Brem Neuro-oncology Program, H. Lee Mof®tt Cancer Center, and Division of Neurosurgery, University of South Florida, Tampa, FL 33612, USA The Third Annual Cambridge Healthtech Insti- tute symposium, entitled `Angiogenesis Antago- nists: Current Clinical Trials, Drug Development and Regulatory Issues', co-sponsored by the jour- nal Angiogenesis and the Angiogenesis Foundation, convened on October 19 and 20 in Bermuda. The meeting attracted international experts from aca- demia, the biopharmaceutical industry and the National Cancer Institute to share initial experi- ences in clinical trials of therapeutic modulation of angiogenesis. As molecular inhibitors move rap- idly from the laboratory to the clinic, practical strategies were advanced to accelerate the intro- duction of the emerging class of pharmacological agentsÐangiogenesis antagonists. Themes of the meeting included: (1) An update of current clinical trials. (2) Speci®c disease/organ sites selected for anti-an- giogenesis therapy. (3) Potential and actual toxicities. (4) The use of drug synergisms, combining angio- genesis antagonists with cytotoxic therapy. (5) Mechanisms for funding. (6) Overcoming regulatory hurdles to introduce new compounds. Introduction: an emerging new era in clinical medicine William Li, of the Angiogenesis Foundation in Cambridge, Massachusetts, gave the keynote address on `Anti-angiogenic Therapy: An Emerging New Era in Clinical Medicine'. Dr Li noted that due to the pioneering work of Dr Judah Folkman, 1±3 several human diseases 4±6 are perfect targets for therapeutic control of angio- genesis, including cancer, rheumatoid arthritis, ocular neovascularization, psoriasis and AIDS- related Kaposi's sarcoma. In addition, molecular revascularization, 7 using angiogenic growth fac- tors vascular endothelial growth factor (VEGF) and basic ®broblast growth factor (bFGF), shows promise in clinical trials at Boston's Beth Israel Hospital for the treatment of human ischemic limbs and also in experimental models to improve blood ¯ow to the porcine cardiac muscle. In the past 5 years, more than 20 experi- mental anti-angiogenic compounds have entered human clinical trials. The early clinical results suggest that angiosuppressive therapy will prove valuable to control or stabilize metastatic carci- noma, primary brain tumors, prostate cancer, Kaposi's sarcoma and diabetic retinopathy. Dr Li stressed that the successful development of angiotherapy requires a coordinated effort be- tween scientists, clinicians, industry and regula- tory agencies. Recommendations made by the Angiogenesis Foundation for drug development include: (1) Identi®cation of `Optimal Biological Dose' as a new end-point rather than `Maximal Tolerable Dose' for phase I±II clinical trials. (2) Anticipation of a requirement for long-term treatment in order to achieve responses. (3) Consideration of potential drug interactions of other medications the patient takes that could confound interpretation of results because of unknown effects on angiogenesis. Correspondence to S. Brem, H. Lee Mof®tt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. Tel: (+1) 813 979-3063; Fax: (+1) 813 979-3068. Angiogenesis 1998; 2; 9±20 Ó 1998 Rapid Science Ltd Angiogenesis á Vol 2 á No 1 á 1998 9