Glasmacher, A., Prentice, A., Gorschluter, M., Engelhart, S., Hahn, C., Djulbegovic, B., & Schmidt-Wold, I.G. (2003). Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: Evidence from a meta-analysis of 3,597 patients. Journal of Clinical Oncology, 21, 4615–4626.

The purpose of the study was to evaluate itraconazole solution or capsules compared with control (no treatment, placebo, oral polyenes, or fluconazole).

Searches were conducted through Cochrane Central Register of Controlled Trials and MEDLINE (January 1966 to July 2003); abstracts from the annual meetings of the American Society of Hematology, Interscience Conference on Antimicrobial Agents and Chemotherapy, European Hematology Association, European Group for Blood and Marrow Transplantation, German and Austrian Society of Hematology and Oncology, and the British Society for Hematology (1994–2003). Reference lists of relevant studies were reviewed. The pharmaceutical manufacturer of itraconazole was contacted.

13 randomized, controlled trials.

3,597 patients (1,812 on itraconazole and 1,785 controls) with hematologic malignancies who were neutropenic (absolute neutrophil count less than 500) following chemotherapy or bone marrow transplantation.

• A statistically significant decrease was found in the incidence of invasive fungal infections in the itraconazole solution group (49% reduction), but not in the itraconazole capsule group.
• A statistically significant decrease existed in the incidence of invasive yeast infections in the itraconazole solution group (60% reduction), but not in the itraconazole capsule group.
• A statistically significant decrease was found in the incidence of proven invasive aspergillus infections in the itraconazole solution group (48% reduction), but not in the itraconazole capsule group
• A statistically significant decrease was noted regarding mortality in the itraconazole solution group (42% reduction), but not in the itraconazole capsule group.
• No significant difference existed between the groups regarding mortality from any cause during the study period.

Antifungal prophylaxis with an itraconazole solution for neutropenic patients with hematologic malignancies reduces invasive fungal infections, invasive yeast infections, invasive aspergillus infections, and mortality. Bioavailability and dosing are significant factors because benefits are only derived from the oral or IV cyclodextrin solution and not the capsules.

The capsules are not recommended and the dosing should be at least 400 mg per day of the oral cyclodextrin solution or 200 mg per day of the IV solution.