Antibacterial Prophylaxis after Chemotherapy for Solid Tumors and Lymphomas
Michael Cullen, M.D., Neil Steven, Ph.D., Lucinda Billingham, Ph.D., Claire Gaunt, B.Sc., Mark Hastings, M.D., Peter Simmonds, M.D., Nicholas Stuart, M.D., Daniel Rea, Ph.D., Mark Bower, Ph.D., Indrajit Fernando, M.D., Robert Huddart, Ph.D., Simon Gollins, D.Phil., Andrew Stanley, M.R.Pharm.S., for the Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/– Antibiotic in a Number of Tumours (SIGNIFICANT) Trial Group
Background The role of prophylactic antibacterial agents afterchemotherapy remains controversial.
Methods We conducted a randomized, double-blind, placebo-controlledtrial in patients who were receiving cyclic chemotherapy forsolid tumors or lymphoma and who were at risk for temporary,severe neutropenia (fewer than 500 neutrophils per cubic millimeter).Patients were randomly assigned to receive either 500 mg oflevofloxacin once daily or matching placebo for seven days duringthe expected neutropenic period. The primary outcome was theincidence of clinically documented febrile episodes (temperatureof more than 38°C) attributed to infection. Secondary outcomesincluded the incidence of all probable infections, severe infections,and hospitalization but did not include a systematic evaluationof antibacterial resistance.
Results A total of 1565 patients underwent randomization (784to placebo and 781 to levofloxacin). The tumors included breastcancer (35.4 percent), lung cancer (22.5 percent), testicularcancer (14.4 percent), and lymphoma (12.8 percent). During thefirst cycle of chemotherapy, 3.5 percent of patients in thelevofloxacin group had at least one febrile episode, as comparedwith 7.9 percent in the placebo group (P<0.001). During theentire chemotherapy course, 10.8 percent of patients in thelevofloxacin group had at least one febrile episode, as comparedwith 15.2 percent of patients in the placebo group (P=0.01);the respective rates of probable infection were 34.2 percentand 41.5 percent (P=0.004). Hospitalization was required forthe treatment of infection in 15.7 percent of patients in thelevofloxacin group and 21.6 percent of patients in the placebogroup (P=0.004). The respective rate of severe infection was1.0 percent and 2.0 percent (P=0.15), with four infection-relateddeaths in each group. An organism was isolated in 9.2 percentof probable infections.
Conclusions Among patients receiving chemotherapy for solidtumors or lymphoma, the prophylactic use of levofloxacin reducesthe incidence of fever, probable infection, and hospitalization.
Source Information
From University Hospital Birmingham Cancer Centre, Birmingham (M.C., I.F.); Ysbyty Gwynedd, Bangor (N.S.); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham (N.S., L.B., C.G., D.R.); the National Public Health Service Wales, Microbiology, Cardiff (M.H.); Royal South Hampshire Hospital, Southampton (P.S.); Glan Clwyd, Rhyl (S.G.); Chelsea and Westminster Hospital, London (M.B.); Royal Marsden Hospital, London (R.H.); and City Hospital, Birmingham (A.S.) — all in the United Kingdom.
Address reprint requests to Dr. Cullen at University Hospital Birmingham NHS Foundation Trust, Birmingham B15 2TH, United Kingdom, or at michael.cullen{at}uhb.nhs.uk.
Antibacterial Prophylaxis in Patients with Cancer and Neutropenia
Freifeld A. G., Sepkowitz K. A., Almyroudis N. G., Segal B. H., Castagna L., Santoro A., Pasqualotto A. C., Rosa D. D., Machado A. L., Ito J. I., Tegtmeier B. R., O'Donnell M. R., Eller P., Pechlaner C., Del Favero A., Bucaneve G., Martino P., Steven N., Billingham L., Cullen M., Baden L. R.
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N Engl J Med 2006;
354:90-94, Jan 5, 2006.
Correspondence
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