The results of a final analysis of a phase 3 trial comparing antifungal prophylaxis with caspofungin vs fluconazole in children and adolescents undergoing chemotherapy for the treatment of acute myeloid leukemia (AML) revealed a significantly lower rate of invasive fungal disease among patients in the caspofungin arm.  The findings from this study were published in JAMA.1

Although antifungal prophylaxis with posaconazole is recommended in clinical practice guidelines for adults with AML at risk of prolonged chemotherapy-related neutropenia, a reliable pediatric dosing schedule for posaconazole is lacking. Alternatively, fluconazole has been recommended in this setting for younger patients with AML.2

This large, multicenter, open-label, randomized study ( Identifier: NCT01307579) compared the efficacy and safety of fluconazole, an antiyeast agent, with caspofungin, an antifungal agent that covers both yeasts and mold, in pediatric, adolescent, and young adult patients with AML treated with chemotherapy. The primary outcome measure was the percentage of patients in each study arm with invasive fungal disease.

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The study design included 2 interim efficacy analyses. The findings of a subsequent unplanned futility analysis, prompted by results from the planned second interim analysis including 394 patients, were suggestive of futility.  Hence, the trial was closed early prior to full accrual.

The final study analysis included 260 and 257 patients, aged younger than 1 year to 26 years, who were randomly assigned to the fluconazole and caspofungin arms, respectively. Baseline characteristics included a median age of 9 years and a diagnosis of de novo or newly diagnosed AML in over 85% of patients.

Contrary to earlier findings, at the final analysis, the 5-month cumulative incidence of invasive fungal disease was significantly lower for patients in the caspofungin arm compared with those receiving fluconazole (3.1% vs 7.2%; P =.03).

In addition, the cumulative incidence of invasive aspergillosis infection was 0.5% and 3.1% for patients receiving caspofungin and fluconazole, respectively (P =.046).

Regarding treatment toxicity, 32.8% of patients treated with caspofungin and 38.4% of those receiving fluconazole experienced at least one grade 4 or 5 nonhematologic adverse event during chemotherapy cycles 1 to 5.  Hypokalemia, respiratory failure, and elevated alanine transaminase were the most commonly reported adverse events.

In summarizing the results of this study, the study authors noted that “the findings suggest that caspofungin may be considered for prophylaxis against invasive fungal disease, although study interpretation is limited by early termination due to an unplanned interim analysis that appeared to have suggested futility.”


  1. Fisher BT, Zaoutis T, Dvorak CC, et al. Effect of caspofungin vs fluconazole prophylaxis on invasive fungal disease among children and young adults with acute myeloid leukemia: A randomized clinical trial. JAMA. 2019;322(17):1673-1681.
  2. Science M, Robinson PDMacDonald T, Rassekh SR, Dupuis LL, Sung L. Guideline for primary antifungal prophylaxis for pediatric patients with cancer or hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2014;61(3):393-400.