Vincristine toxicity with co-administration of fluconazole during induction therapy for pediatric acute lymphoblastic leukemia.
BACKGROUND
Antifungal prophylaxis is recommended for patients with acute lymphoblastic leukemia (ALL) during high-risk periods such as induction; however, increased vincristine toxicities have been reported with the co-administration of triazole antifungals. We sought to determine whether vincristine-associated toxicities are higher among children with ALL concurrently given fluconazole prophylaxis compared to no prophylaxis.


METHODS
Using a retrospective cohort design, we reviewed records of pediatric patients treated for newly diagnosed ALL from 2003 to 2013. Patients were classified by fluconazole exposure during induction. The development of vincristine-associated toxicity and vincristine dose adjustment were the primary outcomes evaluated. The adjusted risk difference (RD) for vincristine-related toxicity associated with triazole exposure was determined.


RESULTS
We identified 197 patients meeting inclusion criteria for evaluation, 160 (81%) of whom received fluconazole prophylaxis. Among patients receiving fluconazole, 36/160 (22%) developed vincristine toxicity compared to 7/37 (19%) among those not receiving prophylaxis (RD: 3%, 95% confidence interval [CI] -11 to 18%). Adjusting for patient age and race, no statistically significant increased risk for vincristine-associated toxicity with fluconazole exposure was observed (RD 5%, 95% CI -8 to 17%). An increased risk for vincristine-associated toxicity was independently associated with age 10 years or older (RD 19%, 95% CI 4-34%).


CONCLUSIONS
Co-administration of fluconazole during induction therapy for pediatric ALL does not significantly increase the risk for vincristine-associated toxicities; however, patients 10 years or older are at an increased risk for toxicity independent of fluconazole exposure. Prophylaxis with fluconazole during induction therapy for pediatric ALL, if warranted, appears to be a safe clinical practice.
Division of Pediatric Hematology/Oncology, Chapel Hill, North Carolina.|UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
Andrew B
AB
Smitherman
Department of Pharmacy, UNC Hospitals, Chapel Hill, North Carolina.
Cassidy B
CB
Faircloth
UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
Allison
A
Deal
UNC School of Medicine, Chapel Hill, North Carolina.
Michael
M
Troy
Division of Pediatric Hematology/Oncology, Chapel Hill, North Carolina.|UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
Stuart H
SH
Gold
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects* / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D014750:Vincristine; D015725:Fluconazole
fluconazole; leukemia; pediatrics; vincristine