NEW ORLEANS -- A new therapy developed by Genentech for treating cancer by starving tumors has shown troubling side effects, killing four patients who experienced sudden bleeding in their lungs, researchers said on Tuesday.
The researchers are scrambling to find out whether there was something special about those patients. The researchers said they hoped there would be a way to identify in advance those patients who might be prone to the lung bleeds to keep them from using the treatment, known as anti-VEGF.
The treatment, which uses a targeted antibody against one of the proteins that tumors use to grow and spread, had been highlighted at the annual meeting of the American Society of Clinical Oncology in New Orleans.
Researchers say they are still impressed by how the drug, known formally as monoclonal antibody targeted against vascular endothelial cell growth factor (rhuMAb-VEGF), works.
Dr. Russell DeVore of Vanderbilt University in Tennessee tested 99 patients with advanced lung cancer who had not received any treatment. Researchers divided the subjects into three groups, who were given standard chemotherapy, chemotherapy plus a low dose of anti-VEGF or chemotherapy plus a high dose of anti-VEGF.
Without treatement of advanced non-small-cell lung cancer, more than 80 percent of patients die, usually within a year and a half.
But 18 months later, nine of the patients in DeVore's trial are still alive. Median survival was 14 months in the patients who received chemotherapy alone, 12 months in those who were given chemotherapy plus the low dose of anti-VEGF, and 18 months in the group that received the higher anti-VEGF dose.
There were no major side effects at first, but then six patients developed sudden bleeding in their lungs, researchers said.
"Four patients died from that bleeding," DeVore said. "The bleeding that occurred was very concerning.... The bleeding came on suddenly in most of these patients."
DeVore said four of the patients who suffered bleeding had a relatively uncommon sub-type of non-small-cell lung cancer called squamous cell carcinoma.
"It tends to involve large cancers in the central part of the airway," he said.
An autopsy performed on one patient showed that the blood vessels in that large tumour had withered away, which perhaps had made the tumor more unstable and more likely to break up, which would be expected to cause bleeding.
Dr. Michael Gordon of the University of Arizona agreed that the tumors in these patients might be unstable.
"Perhaps we could exclude these patients or do some type of therapy to prevent the bleeding," DeVore said.
Other experts agreed that the bleeding incidents, ironically, may show that the anti-VEGF is working.
"This may be some proof of concept that the drug is doing what it is supposed to do," DeVore said.
"I feel badly and sad for the side effects the patients had to go through," said Dr. Nicholas Vogelzang, director of the University of Chicago Cancer Research Center. "But this is in the area of what we would expect to see. To inhibit VEGF should give you some bleeding effects."
This is because tissues are constantly building and rebuilding blood vessels, and to interrupt that process could weaken tissues, he said.
Vogelzang said the development will strain companies developing such drugs. Perhaps, he said, the companies will be responsible for screening patients who might suffer bad side effects.
The bleeding was not seen in patients with other cancers.
"We see evidence, early evidence, of potential action of slowing tumor progression in lung cancer, colon cancer, and breast cancer," DeVore said. He said none of those patients experienced the bleeding side effects.
"We think this is enough proof of concept to move ahead to Phase III trials in these tumour groups," DeVore said.
Monoclonal antibodies are relatively new cancer therapies based on a genetically engineered protein that homes in on a specific target.
In this case the target is VEGF, which is used to build blood vessels and which tumors use to build new capillaries to tap into arteries to feed themselves. This process, called angiogenesis, and drugs that interfere with it, called angiogenesis inhibitors, are a hot topic in cancer research.
