TUESDAY, Feb. 1 (HealthDay News) -- A new review finds more evidence that the beleaguered cancer drug Avastin may harm patients.

An analysis of previously published studies found that the drug, when used in combination with chemotherapy or biological therapy, actually increased patient deaths from adverse events, compared with using chemotherapy or biologics alone.

This new information should change the way patients and practitioners think about the drug, said Dr. Shenhong Wu, senior author of the report, published Feb. 2 in the Journal of the American Medical Association.

"I believe the risk-benefit ratio has changed," said Wu, assistant professor of medicine at Stony Brook University Medical Center in Stony Brook, N.Y. "Physicians need to think about this."

Avastin (bevacizumab) was okayed in 2008 for use in conjunction with chemotherapy to treat breast cancer under the U.S. Food and Drug Administration's accelerated approval program. Approval was based on one clinical trial in patients with metastatic HER2-negative breast cancer that found a benefit in terms of cancer recurrence -- but not overall survival -- and was contingent on further data to confirm the results.

Three subsequent studies failed to find an overall survival benefit and, in fact, showed less impressive improvements in survival involving no progression of cancer.

After reviewing all four studies, the FDA in December recommended revoking approval of Avastin to fight breast cancer. The recommendation didn't affect use of Avastin for advanced colon, lung, kidney and brain cancer.

Wu and his colleagues looked at 16 completed randomized controlled trials on Avastin involving more than 10,000 patients with different forms of cancer.

Some 2.5 percent of patients taking Genentech-made Avastin died compared with 1.7 percent of those taking chemotherapy alone, a 46 percent increased risk, the investigators found.

The rate was about the same across tumor types but not across different chemotherapy regimens. The risk was increased among those receiving chemotherapy containing taxanes or platinum agents but not other chemo compounds.

The most common causes of death were hemorrhage, followed by low white-blood-cell count and gastrointestinal perforations.

Dr. Roman Perez-Soler, chairman of oncology and chief of medical oncology at Montefiore Medical Center in New York City, a lung cancer expert, pointed out that lung cancer is one of the few malignancies in which Avastin has prolonged survival and thus might still have a place in this armamentarium.

But an accompanying journal editorial raises other considerations, including the cost ($50,000 a year for the drug alone, plus the cost of monitoring and chemo) and a cumbersome delivery method (frequent injections for years).

The author of that editorial acknowledged that Avastin works well in some patients, but said it's impossible to predict in which patients and for how long benefits will last.

More information

The U.S. National Library of Medicine has more on Avastin.