Kanda, Y., Yamamoto, R., Chizuka, A., Hamaki, T., Suguro, M., Arai, C., . . . Togawa, A. (2000). Prophylactic action of oral fluconazole against fungal infection in neutropenic patients. A meta-analysis of 16 randomized, controlled trials. Cancer, 89, 1611–1625.

To evaluate the efficacy of fluconazole prophylaxis during chemotherapy-induced neutropenia.

Databases searched were MEDLINE, CancerLit, and the Pfizer company database through April 1999 (no start date was provided). The search was not restricted to the English language or published trials.

Sixteen trials were evaluated.

Studies were included if they

• Were prospective and randomized.
• Compared oral fluconazole with placebo, no treatment, or oral polyenes (nystatin, oral amphotericin B).
• Used a neutropenia definition of less than 1000/mcl and did not use intravenous (IV) antifungals.
• Reported the incidence of fungal infection.

Data from the meta-analyses reported the combined population, bone marrow transplant (BMT) recipients only, and non-BMT recipients only.

A total of 3,734 patients were evaluated. Some studies exclusively examined BMT recipients, others studied non-BMT recipients, and others evaluated a combined population.

Prophylactic fluconazole was not effective in

• Reducing fungal-related death in non-BMT recipients (although it was effective in BMT recipients).
• Reducing proven systemic fungal infections in non-BMT recipients (although it was effective in BMT recipients).

Prophylactic fluconazole was effective in

• Reducing superficial fungal infections in non-BMT and BMT recipients.
• Reducing the use of amphotericin B for persistent neutropenic fever in the BMT population (this could not be concluded for the non-BMT group).

Prophylactic fluconazole did not increase rates of proven systemic infection with resistant strains in the non-BMT or BMT populations.

Colonization of fluconazole-resistant fungi increased with prophylactic treatment in BMT recipients; however, information about non-BMT recipients is inconclusive because of lack of power and paucity of data.