Inhibition of angiogenesis for the treatment of metastatic melanoma.

Metastatic malignant melanoma is a uniformly fatal disease. Tumor growth and metastasis are associated with angiogenesis and lymphangiogenesis. Proangiogenic factors are associated with higher disease burdens and worse outcomes in melanoma. Accordingly, many agents that target angiogenesis have been studied in melanoma. Angiogenesis is a complex, multifaceted process with many potential therapeutic targets. So far, monoclonal antibodies, immune conjugates, tyrosine kinase inhibitors, immunomodulatory agents, and other therapies have been tested in the phase 2 or phase 3 setting for the treatment of metastatic melanoma. The antiangiogenic agents that have been tested to date offer little activity as single agents, but in combination with cytotoxic agents prolong progression-free survival. We explore data from published phase 2 and phase 3 trials in addition to the purported mechanisms of action of antiangiogenic agents.