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Rational Selection of Patients for Antibacterial Prophylaxis After Chemotherapy

Michael H. Cullen, Lucinda J. Billingham, Claire H. Gaunt, Neil M. Steven

From the University Hospital Birmingham Cancer Centre; Cancer Research UK, Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom

Address reprint requests to Michael Cullen, MD, University Hospital Birmingham, NHS Foundation Trust, Birmingham B15 2TH, United Kingdom; e-mail: michael.cullen{at}uhb.nhs.uk

Purpose The SIGNIFICANT (Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy ± Antibiotic in a Number of Tumours) trial reported a reduction in febrile episodes (FEs) among 1,565 patients with solid cancers and lymphomas receiving cyclical, myelosuppressive chemotherapy (causing grade 4 neutropenia) in a randomized, placebo-controlled, double-blind trial of levofloxacin (P = .01). In response to concerns that increased antibacterial prescribing selects for microbial resistance, we examined our data to explore the rationale for more limited prophylaxis.

Patients and Methods The risk of FE was calculated for control patients on first versus nonfirst cycles, with or without first-cycle FE, and within subgroups defined by cancer type, performance status (PS), age, and treatment context (adjuvant v nonadjuvant). Using the randomized trial data, the prophylactic efficacy of levofloxacin was examined for the same subgroups.

Results The per-cycle FE incidence was much lower on nonfirst (3.3%) versus first cycles (8.0%). Prophylaxis was less effective for nonfirst (odds ratio [OR] = 0.78; P = .16) compared with first cycles (OR = 0.42; P < .001). However, FE on cycle 1 predicted a much higher risk of FE and a trend to continued prophylactic efficacy on subsequent cycles. FE rate was greatest for testicular cancer (27.9%), then small-cell lung cancer (17.3%), and lowest for breast cancer (11.5%). Prophylactic efficacy was consistent across age, sex, PS, treatment context, and disease type (except possibly non-Hodgkin's lymphoma).

Conclusion Under pressure to limit antibacterial use, these exploratory data support offering prophylactic levofloxacin on cycle 1 only of myelosuppressive cancer chemotherapy and on subsequent cycles after a cycle-1 fever. Prophylactic levofloxacin is effective regardless of age, PS, or tumor type.

Supported by an educational grant and trial medication for the SIGNIFICANT Trial, which was an investigator-led trial, from Hoechst Marion Roussel (now part of Sanofi Aventis) and by a core grant to the Institute of Cancer Studies Clinical Trials Unit, Birmingham, from Cancer Research UK.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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