Antibiotic Could Make Chemotherapy Safer

But added cost and raised risk of drug resistance may limit its use, experts say

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By Serena Gordon
HealthDay Reporter

WEDNESDAY, Sept. 7, 2005 (HealthDay News) -- Since bacterial infections are a common -- sometimes even deadly -- side effect of chemotherapy treatment, would it make sense to use antibiotics to prevent those infections?

Maybe, conclude a pair of new studies in the Sept. 8 issue of the New England Journal of Medicine.

Both studies found some benefit to using antibiotics to prevent infections in people receiving chemotherapy, but the studies' researchers and other experts point out that the benefit may be too small when compared to the cost of the drugs and the risk of developing antibiotic resistance.

"These studies are well designed and suggest that a number of bad outcomes, such as fevers, infections and hospitalizations, could be reduced [with prophylactic use of levofloxacin], but that reduction comes at a cost in terms of actual dollars, in terms of side effects, and in terms of the possibility of developing antibiotic resistance," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

Infections sometimes occur during and after chemotherapy treatment because the same drugs that kill cancer cells can also affect healthy cells. Infection-fighting white blood cells are often depleted by chemotherapy, especially white blood cells called neutrophils.

When chemotherapy or radiation therapy reduces the numbers of neutrophils significantly, a condition called neutropenia develops. Patients with neutropenia are at increased risk of infection, according to National Cancer Institute experts.

In the United States, doctors routinely treat patients undergoing chemotherapy with granulocyte colony-stimulating factor (G-CSF), a therapy that helps stimulate the growth of white blood cells, explained Dr. Bruce Raphael, a hematologist/oncologist at the New York University Cancer Institute in New York City.

But, whether or not using preventive antibiotic therapy would further reduce the rate of infections, hospitalizations and deaths was still an open question, Lichtenfeld said. One recent study estimated that the routine prophylactic use of antibiotics for chemotherapy patients may already be as high as 45 percent.

In the first of two studies in this week's journal, researchers in Italy compared the use of levofloxacin (Levaquin) to an inactive placebo in 760 people diagnosed with chemotherapy-induced neutropenia. In the study, 384 people received 500 milligrams of levofloxacin daily from the start of chemotherapy until their neutropenia disappeared.

According to a team led by Dr. Giampaolo Bucaneve of Policlinico Monteluce, Perugia, 85 percent of those on the placebo developed a fever -- indicating a possible infection -- while just 65 percent of those taking levofloxacin did. There was no statistically significant improvement in patient death rates, however.

"These researchers concentrated on a group of patients we know develop neutropenia, sometimes for weeks at a time," said Raphael. "The questions you have to ask are, could they reduce the number of infections? Yes, they did, but at what cost? Are you inducing resistant bugs?"

The second study, this time led by Dr. Michael Cullen of University Hospital Birmingham Cancer Centre in the United Kingdom, included patients who weren't as sick as those in the first study, meaning that they needed lower doses of chemotherapy to treat their disease. And, as the dose of chemotherapy dropped, so too did their risk for neutropenia.

This study included 1,565 cancer patients randomly assigned to receive placebo treatment or treatment with 500 milligrams of levofloxacin for seven days, at a period where they were thought to be at high risk for neutropenia.

During the first cycle of chemotherapy, 7.9 percent of those on the placebo developed fever compared to just 3.5 percent of those taking levofloxacin. Hospitalizations for infection occurred in 15.7 percent of those receiving levofloxacin compared to 21.6 percent of those on placebo, the researchers report.

There were four infection-related deaths in each of the two groups, according to the study.

"Here, they're treating a huge number of patients with antibiotics to prevent a small number of infections," said Raphael. "The rate of infection was only about 8 percent for placebo. They did reduce the number of infections by as much as 50 percent [with levofloxacin], but many people took the drug and didn't need it."

Plus, Raphael pointed out that G-CSF wasn't given as prophylaxis in this study to boost white cell counts, as is commonly done in the United States.

In an accompanying editorial, Dr. Lindsey Baden, the deputy editor of the New England Journal of Medicine wrote, "[These studies] provide evidence of the significant benefit of levofloxacin prophylaxis, but the price of this benefit may be high."

Because of the added risk of antibiotic resistance, Baden suggested that a more targeted approach might be warranted. Lichtenfeld and Raphael concurred.

"If it works, why not concentrate on those who most likely need it -- people who have been shown to have a low white blood cell count during the first cycle, people who are older, people who have bone marrow involvement?" said Raphael. "In these groups, this approach appears to be very reasonable." He added that patients would also need to be monitored to ensure that antibiotic resistance wasn't developing.

The bottom line? "I don't see a need to treat every patient who has chemotherapy with antibiotics," said Raphael.

Lichtenfeld added that cancer patients should know that this is an option -- and discuss with their doctor whether or not it's a good choice for them.

More information

To learn more about chemotherapy and its side effects, visit the American Cancer Society.

SOURCES: Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta, Ga.; Bruce Raphael, M.D., hematologist/oncologist, New York University Cancer Institute, and clinical professor, medicine, New York University School of Medicine, New York City; Sept. 8, 2005 New England Journal of Medicine

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