Mandhaniya, S., Swaroop, C., Thulkar, S., Vishnubhatla, S., Kabra, S.K., Xess, I., & Bakhshi, S. (2011). Oral voriconazole versus intravenous low dose amphotericin B for primary antifungal prophylaxis in pediatric acute leukemia induction: A prospective, randomized, clinical study. Journal of Pediatric Hematology/Oncology, 33, e333–e341.

The purpose of the study was to compare the efficacy and toxicity of oral voriconazole to IV low-dose amphotericin B in pediatric patients with acute leukemia.   

Oral variconazole was administered at a dose of 6 mg/kg per dose for initial two doses followed by 4 mg/kg per dose twice daily one hour before meals. Low-dose IV amphotericin B was administered at a dose of 0.5 mg/kg per day three times a week. Before administration of amphotericin B all patients received diphehydramine IV and oral paracetamol as premedication and saline hydration post infusion. Systemic antifungals were not allowed for use before patients underwent the trial. Complete blood count, liver function tests, and renal function tests were done at least twice weekly until seven days after completion or failure.

• The sample consisted of 100 patients aged 15 years or younger. 
• Males were 75% of the sample, females were 25%
• Key disease characteristics included acute myeloid and acute lymphoblastic leukemias.
• Before induction chemotherapy, patients were eligible if they had no pneumonia on chest radiograph and no systemic antifungal therapy within seven days of randomization. Febrile patients who were hemodynamicaly stable with a normal chest radiograph also were included in the study.

• Single site
• Inpatient
• New Dehli, India
   

• The phase of care was active treatment
• The application was pediatrics.
   

Randomized, non-stratified, open-label, single-institution pilot study.

• EORTC/MSG criteria for definition and classification of proven, probable, and possible invasive fungal infection.    
• Hepatic toxicity was defined as liver function test values greater than 5 times the upper limit of normal.
• Renal toxicity is defined as creatinine greater than 2 mg/dl.
   

The overall probable, proven, and possible fungal infections were 5% in the study.  In the voriconazole arm, 28% had failure of prophylaxis compared to 34% failure rate in the amphotericin B arm. No differences were noted between groups in proven, probable, and possible fungal infections. Those receiving the voriconazole had significantly less toxicity, with 6% of patients in variconazole arm having any serious adverse event (SAE)  compared to 31% in the amphotericin B arm (hypokalemia) (p < 0.001). With the amphotericin B arm, 50% had infusion reactions.

 Oral voriconazole seemed to be comparable with amphotericin B, with less toxicity and more convenience.

• The empirical dose of varicanozole is an extrapolation of adult dose.
• The authors did not perform pharmacokinetics of the patients to show whether the empirical dose of variconazole administered was efficacious or not.
• There was no blinding in the study, with inherent risk of bias.

Potential increased need for patient and caregiver education regarding oral medication administration. Continued research in comparable efficacy of antifungal agents will be helpful in order to select effective agents that are least toxic, practical, and cost effective.