Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials.
BACKGROUND
The overall clinical efficacy of the azoles antifungal agents and low-dose intravenous amphotericin B for antifungal chemoprophylaxis in patients with malignant disease who have severe neutropenia remains unclear.


METHODS
Randomized-controlled trials of azoles (fluconazole, itraconazole, ketoconazole, and miconazole) or intravenous amphotericin B formulations compared with placebo/no treatment or polyene-based controls in severely neutropenic chemotherapy recipients were evaluated using meta-analytical techniques.


RESULTS
Thirty-eight trials that included 7014 patients (study agents, 3515 patients; control patients, 3499 patients) were analyzed. Overall, there were reductions in the use of parenteral antifungal therapy (prophylaxis success: odds ratio [OR], 0.57; 95% confidence interval [95% CI], 0.48-0.68; relative risk reduction [RRR], 19%; number requiring treatment for this outcome [NNT], 10 patients), superficial fungal infection (OR, 0.29; 95% CI, 0.20-0.43; RRR, 61%; NNT, 12 patients), invasive fungal infection (OR, 0.44; 95% CI, 0.35-0.55; RRR, 56%; NNT, 22 patients), and fungal infection-related mortality (OR, 0.58; 95% CI, 0.41-0.82; RRR, 47%; NNT, 52 patients). Invasive aspergillosis was unaffected (OR, 1.03; 95% CI, 0.62-1.44). Although overall mortality was not reduced (OR, 0.87; 95% CI, 0.74-1.03), subgroup analyses showed reduced mortality in studies of patients who had prolonged neutropenia (OR, 0.72; 95% CI, 0.55-0.95) or who underwent hematopoietic stem cell transplantation (HSCT) (OR, 0.77; 95% CI, 0.59-0.99). The multivariate metaregression analyses identified HSCT, prolonged neutropenia, acute leukemia with prolonged neutropenia, and higher azole dose as predictors of treatment effect.


CONCLUSIONS
Antifungal prophylaxis reduced morbidity, as evidenced by reductions in the use of parenteral antifungal therapy, superficial fungal infection, and invasive fungal infection, as well as reducing fungal infection-related mortality. These effects were most pronounced in patients with malignant disease who had prolonged neutropenia and HSCT recipients.
Department of Internal Medicine, the University of Manitoba and CancerCare Manitoba, Winnipeg, Manitoba, Canada. ebow@hsc.mb.ca
Eric J
EJ
Bow
Michel
M
Laverdière
Nathalie
N
Lussier
Coleman
C
Rotstein
Mary S
MS
Cheang
Stratis
S
Ioannou
D000935:Antifungal Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009181:Mycoses / Q000517:prevention & control*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D009503:Neutropenia / Q000150:complications*; D016032:Randomized Controlled Trials as Topic
D000935:Antifungal Agents; D000970:Antineoplastic Agents