TUESDAY, Jan. 4 (HealthDay News) -- Just weeks after U.S. health
officials moved to rescind approval of the drug Avastin to treat
breast cancer, a new study provides more evidence that the
anti-cancer medication ups the odds of congestive heart failure in
The meta-analysis, published online Jan. 4 in the
Journal of Clinical Oncology, included almost 4,000 patients and found a small but significant number developed heart failure.
"We wanted to raise the issue in the daily practice of oncologists -- if they're not aware of this they cannot easily make the connection," noted the study's lead author, Dr. Toni Choueiri, an attending oncologist at the Dana-Farber Cancer Institute in Boston. He added that the findings were particularly troubling since the patients in the study tended to start out relatively heart-healthy but then progressed to signs of heart failure.
Last month, the U.S. Food and Drug Administration announced
plans to revoke approval of bevacizumab (Avastin) for treating
breast cancer, although not for other indications. The move was
based on evidence that the drug doesn't prolong overall survival in
breast cancer patients and poses a risk of serious side
"What we see with Avastin in terms of its cardiac toxicity, frankly, it's not that unusual in cancer chemotherapy," said Dr. William Abraham, a heart failure specialist and director of cardiovascular medicine at Ohio State University Medical Center in Columbus, who is familiar with the study. "It turns out that many of the systemic anti-cancer treatments have detrimental effects on the cardiovascular system."
According to Abraham, Avastin actually was less likely to cause
heart failure than some other widely used breast cancer drugs, in
particular the class of chemotherapy agents known as
anthracyclines. But the FDA's decision was based on the totality of
evidence, he said, citing possible side effects such as
perforations of the nose, stomach and intestine; high blood
pressure; and heart failure.
The damage caused by Avastin appears to be reversible after the
drug is stopped. Damage from anthracyclines is not, according to
the study, conducted by researchers at the Dana-Farber Cancer
Institute and Harvard Medical School in Boston.
In this new review of studies, which included 3,784 patients,
1.6 percent of patients taking Avastin developed heart failure,
which the authors characterized as "reasonably low."
Yet the relative risk compared to placebo was almost five times
as high in Avastin patients. No differences emerged between high
and low doses of the drug.
By contrast, some 25 percent to 30 percent of patients taking
Avastin develop high blood pressure, 5 percent of them severe
hypertension, Abraham said. And about 4 percent to 5 percent
develop blood clots, he added.
"From the heart failure standpoint, Avastin is certainly no worse and in many instances better than some other chemotherapy agents that are used to treat cancer in general or breast cancer in particular," Abraham said. "But if you look at totality of data, hypertension, severe hypertension and thromboembolic [blood-clotting] events, there seems to be overall increase in cardiac deaths in these patients. When you take all of that together, it really raises the red flag."
The issue of harm vs. benefit weighs heavily on the minds of
cancer experts, they added.
"When we have drugs that have small values, which is what Avastin is in the therapeutic setting, we really better be sure that these drugs are helping our patients and not doing some harm," said Dr. Jay Brooks, chairman of hematology/oncology with Ochsner Health System in Baton Rouge, La.
"Unfortunately, Avastin has proved to be not as good as we thought it would be," he added. "It was put on the market on accelerated approval and when we do things quickly sometimes, when there's a huge push to get it out to the public, sometimes it backfires."
Avastin's approval for treating breast cancer in 2008 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. Follow-up studies failed to confirm a survival
benefit, which led to the FDA's unusual move in December.
Avastin, made by Genentech, is also approved to treat colorectal
cancer, non-small-cell lung cancer, high-grade gliomas (brain
tumors) and kidney cell cancer. The recent FDA action does not
affect these uses.
The study authors suggested that breast cancer patients might be
more susceptible to side effects from Avastin than some other
cancer patients because of prior or simultaneous use of other
The U.S. National Cancer Institute has more on