Antiangiogenesis research is booming, as questions and studies proliferate.

I n a recent analysis of a large observational study, bevacizumab (Avastin), an inhibitor of angiogenesis, was associated with favorable survival rates in patients whose colorectal cancer had already progressed. Those taking bevacizumab with chemotherapy had a median overall survival of 32 months, compared with 20 months for those who did not receive bevacizumab beyond first-line therapy. The difference was statistically significant. The analysis, published in November, was based on data from a patient registry known as BRiTE, which is designed primarily to gather information on adverse events and secondarily on progression-free and overall survival. Nevertheless, the positive results buoyed researchers. “We did not expect patients to receive such a magnitude of benefi t,” said lead investigator Axel Grothey, M.D. , a professor at the Mayo Clinic in Rochester, Minn. The researchers concluded that bevacizumab beyond initial disease progression might benefi t patients who have metastatic colorectal cancer. But compare the BRiTE results to those of a prospective controlled trial — considered a stronger study design — in patients with metastatic colorectal cancer, also published last year. In this multicenter, phase III trial, patients were randomized to either fi rstline treatment with bevacizumab and chemotherapy until disease progression or chemotherapy alone. Patients taking the combination had a disappointing median overall survival of 21.3 months compared with those taking only chemotherapy, who lived a median 19.9 months. The difference was not statistically signifi cant. The lead investigator in this trial, Leonard Saltz, M.D., at Memorial Sloan – Kettering Cancer Center in New York, is less optimistic than Grothey that the agents will live up to expectations. “Antiangiogenesis is an elegant concept, and bevacizumab, like other angiogenesis inhibitors [AIs], is a real but modest step, but it isn’t a breakthrough drug and it isn’t a home run,” he said. The confl icting results — and attitudes — point to some of the current questions surrounding AIs 5 years after the fi rst one, bevacizumab, was approved by the U.S. Food and Drug Administration. And with many questions unanswered, AI research is booming. There are currently about 800 trials under way, according to David Waxman, Ph.D., professor of medicine at Boston University School of Medicine, writing in the December 2008 Molecular Cancer Therapeutics. Trials are testing the drugs alone and in combination with each other and with chemotherapy agents, as third, second, and more recently fi rst-line therapy. Since 2004, the FDA has approved other AIs, including sunitinib (Sutent) for renal cancer and gastrointestinal stromal tumor and sorafenib (Nexavar) for liver cancer. In March, a phase III trial of sunitinib was stopped early after the drug demonstrated substantially better progression-free survival than placebo in patients with pancreatic neuroendocrine tumors. Other AIs in development include axitinib and vandetanib. Despite such activity, or perhaps because of it, scientists do not agree about the potential of AIs to control cancer, or how to best use them, or even how best to gauge their effi cacy.