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Routine versus selective antifungal administration for control of fungal infections in patients with cancer
Peter C Gøtzsche1, Helle Krogh Johansen
1The Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, 7811, Copenhagen, Denmark, DK-2100.
Background:
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.
Objectives:
To assess whether commonly used antifungal drugs decrease mortality in cancer patients with neutropenia.
Search Methods:
We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
Selection Criteria:
Randomised clinical trials of amphotericin B, fluconazole, ketoconazole, miconazole, itraconazole or voriconazole compared with placebo or no treatment in cancer patients with neutropenia.
Data Collection And Analysis:
The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.
Main Results:
Thirty-two trials involving 4287 patients were included. Prophylactic or empirical treatment with amphotericin B significantly decreased total mortality (relative risk (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96), whereas the estimated RRs for fluconazole, ketoconazole, miconazole, and itraconazole were close to 1.00. No eligible trials were found with voriconazole. Amphotericin B and fluconazole decreased mortality ascribed to fungal infection (RR 0.45, 95% CI 0.26 to 0.76 and RR 0.42, 95% CI 0.24 to 0.73, respectively). The incidence of invasive fungal infection decreased significantly with administration of amphotericin B (RR 0.41, 95% CI 0.24 to 0.73), fluconazole (RR 0.39, 95% CI 0.27 to 0.57) and itraconazole (RR 0.53, 95% CI 0.29 to 0.97), but not with ketoconazole or miconazole. Effect estimates were similar for those 13 trials that had adequate allocation concealment and were blinded. The reporting of harms was far too variable from trial to trial to allow a meaningful overview. For the 2011 and 2014 updates no additional trials were identified for inclusion.
Authors' Conclusions:
Intravenous amphotericin B was the only antifungal agent that reduced total mortality. It should therefore be preferred when prophylactic or empirical antifungal therapy is introduced in cancer patients with neutropenia.
Insights
Systemic fungal infections are a major risk for cancer patients with neutropenia. Intravenous amphotericin B was the only antifungal drug found to significantly decrease overall mortality in these patients.
Area of Science:
- Oncology
- Infectious Diseases
- Pharmacology
Background:
- Systemic fungal infections pose significant morbidity and mortality risks for cancer patients, especially those with neutropenia.
- Antifungal medications are frequently administered prophylactically or empirically to manage persistent fever in this vulnerable population.
Purpose of the Study:
- To evaluate the efficacy of commonly used antifungal drugs in reducing mortality among neutropenic cancer patients.
- To compare the effectiveness of various antifungal agents, including amphotericin B, fluconazole, ketoconazole, miconazole, and itraconazole, against placebo or no treatment.
Main Methods:
- A systematic literature search was conducted on PubMed and reference lists for randomized clinical trials up to July 2014.
- Included trials compared specific antifungal agents (amphotericin B, fluconazole, ketoconazole, miconazole, itraconazole, voriconazole) with placebo or no treatment in neutropenic cancer patients.
- Data on trial eligibility, risk of bias, and outcomes were independently extracted by two reviewers.
Main Results:
- Thirty-two trials with 4287 patients were analyzed. Amphotericin B significantly reduced total mortality (RR 0.69).
- Fluconazole and amphotericin B demonstrated significant reductions in fungal infection-related mortality (RR 0.42 and RR 0.45, respectively).
- Amphotericin B, fluconazole, and itraconazole significantly decreased the incidence of invasive fungal infections.
Conclusions:
- Intravenous amphotericin B was the sole antifungal agent proven to reduce overall mortality in neutropenic cancer patients.
- Amphotericin B is recommended as the preferred agent for prophylactic or empirical antifungal therapy in this patient group.
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