LI study: Avastin, chemo mix raises risk

When used in combination with conventional chemotherapy, the cancer drug Avastin puts patients at a greater risk of dying from side effects, a team of Stony Brook medical investigators has found.

Raising new questions about the popular medication, Dr. Shenhong Wu and colleagues studied 16 clinical trials involving more than 10,000 patients who received an Avastin/chemo combination, the method most commonly used to administer Avastin.

Their analysis of the most common causes of fatal side effects involving Avastin found that 2.5 percent of patients taking Avastin and undergoing chemo died, compared with 1.7 percent of those taking chemotherapy alone, an increased risk of 47 percentage points.

Nearly a quarter of those patient deaths of those taking Avastin and chemo were due to severe bleeding, the new analysis found. Another 12.2 percent died because their treatment destroyed infection-fighting white blood cells.

"When we consider Avastin for treatment, we have to balance the risk with the benefit," said Wu, a cancer specialist at Stony Brook University Medical Center, who has led a series of studies on Avastin in recent years.

Ed Lang, a spokesman for Avastin's maker, Genentech, said the company welcomes research about Avastin's safety, but he contends Wu's study is flawed because the results include forms of cancer for which Avastin is not approved.

In the study, appearing in Wednesday's Journal of the American Medical Association, Wu found that risks of potentially fatal side effects involve patients across a range of advanced cancers. "We initially thought this drug was less toxic," said Wu, adding that doctors have faced a steep learning curve involving Avastin, a drug approved for colorectal, lung, brain and kidney cancers.

The drug has been found to cause severe bleeding, holes in the bowel and problems with wound healing. In December, federal regulators began the process of withdrawing approval for its use as breast cancer treatment after a research review suggested it failed to help those patients live longer or provide enough benefit to outweigh its risks.

Avastin eliminates tumor blood vessels, blunting the cancer's ability to tap into the host's blood supply to withdraw nutrients. Without sustenance, a cancer, theoretically, cannot grow.

Despite the risks, Wu prescribes the drug for some patients and notes that treatment-related toxicity is also a problem with conventional cancer drugs.

Like other doctors across the country, he has found that Avastin works extraordinarily well in some patients. The problem: Doctors have no way of discerning who will fare best.

Dr. Daniel Hayes of the University of Michigan argues in an accompanying journal editorial that doctors need a way to screen patients and administer Avastin only to those who would benefit most.

"Although [Avastin] has benefit, it is currently not possible to determine in whom or for how long," Hayes said.