Wang, J., Zhan, P., Zhou, R., Xu, J., Shao, X., Yang, Y., & Ouyang, J. (2010). Prophylaxis with itraconazole is more effective than prophylaxis with fluconazole in neutropenic patients with hematological malignancies: A meta-analysis of randomized-controlled trials. Medical Oncology, 27, 1082–1088.

The purpose of this study was to assess the efficacy of fluconazole compared to itraconazole in neutropenic patients with hematologic malignancies.

MEDLINE, EMBASE, the Cochrane-controlled trials register, and the Cochrane Library and Science Citation Index were searched.

Key words included itraconazole, fluconazole, hematologic malignancies, meta-analysis.

Only studies published as an abstract or journal article after 2009 were included. Studies not published as an abstract or in a journal were excluded, as were any studies prior to 2009.

6,574 total reference were retreived. 

Two independent reviewers extracted data and entered that data into a freeware program (Review Manager 5.0). Differences expressed as the risk ratio with 95% confidence interval (CI); heterogeneity was checked by using a Q-test; random effects model was used prior to pooling of data; sensitivity analysis to assess if modification of inclusion criteria affected final result; publication bias was assessed by funnel plots.
 

• After exclusion, 9 studies remained in the total sample. 
• Total amount of subjects was 2,254.
• Size of the sample ranged across studies from 59–581.
• Fluconazole dosing ranged from 100 mg PO daily to 400 mg daily; itraconazole dosing ranged from 2.5 mg/kg every 12 hours to 400 mg per day; no other sample characteristics were given (i.e., age, gender, etc.).

Active treatment

Results suggested that prophylaxis with itraconazole is more effective than prophylaxis with fluconazole in prevention of fungal infections and invasive fungal infections (RR = 1.33, 95% CI [1.02, 1.73], p = 0.03). No differences were noted in overall mortality, fungal-related mortality, or proven fungal infections. Fewer patients on fluconazole were withdrawn from studies due to adverse events (RR = 0.45, 95% CI [0.27, 0.75], p = 0.002).

 As there were no differences in mortality or proven fungal infections, it is unclear what outcome was used that showed a difference in efficacy.

• Heterogeneity is a potential problem
• Dosages and duration of both itraconazole and fluconazole were varied throughout.
• No definitions of outcomes used is provided.

While the results support itraconazole, the medication is associated with higher adverse effects.