Two new double-blind, randomized clinical trials suggest that the prophylactic use of the antibacterial agent levofloxacin can reduce the risk of fever, bacterial infections, and hospitalizations in patients undergoing chemotherapy who are likely to develop neutropenia, a dangerously low white blood cell count. Both studies were published in the September 8 New England Journal of Medicine (NEJM).
The studies - one conducted in Italy, the other in the United Kingdom - had slightly different designs. The Italian study randomized 760 patients about to undergo chemotherapy and who were at risk for prolonged neutropenia (7 days or more) to receive levofloxacin or placebo until the neutropenia resolved. Patients in the
treatment group were less likely to develop a fever, which was the study's primary endpoint because it is indicative of an infection, than those in the placebo group (65 percent vs. 85 percent). Treatment-group patients were also less likely to have documented cases of bacterial infections than the placebo group. Antibacterial prophylaxis did not improve survival compared with placebo.
The second study involved 1,565 patients scheduled to undergo cyclic chemotherapy who were randomized to a placebo or levofloxacin for 7 days when the risk of neutropenia was highest. In the first chemotherapy cycle, 3.5 percent of patients in the treatment group developed a fever, compared with 7.9 percent of those on placebo. Patients on levofloxacin also had lower hospitalization rates, 15.7 percent vs. 21.6 percent. Again, no difference in survival was documented.
The prophylactic use of antibacterial agents has been controversial, especially because of concerns about increasing the spread of drug-resistant bacteria. Neither study was designed to specifically address the issue of resistance, although one study did show an increase in drug-resistant bacteria in those treated with levofloxacin.
"One way to maintain the benefits described in the two current studies but minimize the risk [of bacterial drug resistance] is to restrict its use to those at highest risk," suggested Dr. Lindsey R. Baden, an NEJM deputy editor, in an accompanying editorial. "Efforts to improve risk stratification will be critical to minimize unnecessary use of antimicrobial agents and simultaneously preserve the benefits described in the two studies."
NCI Cancer Bulletin
