Vincristine toxicity with co‐administration of fluconazole during induction therapy for pediatric acute lymphoblastic leukemia

Abstract

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.

Vincristine toxicity with co‐administration of fluconazole: Long‐term concerns

“…To the Editor: I thank Smitherman et al . for their recent article in Pediatric Blood and Cancer , which was a retrospective review comparing rates of vincristine‐related toxicities associated with fluconazole exposure during induction therapy in pediatric patients with acute lymphoblastic leukemia (ALL).…”

“…Fluconazole is a moderate cytochrome P450 3A4 inhibitor and vincristine is extensively metabolized in the liver via cytochrome P450 3A4; thus, there is concern for increased vincristine toxicity in patients receiving co‐administration of fluconazole. Research regarding the clinical implication of this drug–drug interaction has not settled the debate and current clinical practice tends to vary based on the treating medical team …”

“…Smitherman et al . concluded the co‐administration of fluconazole during induction therapy for pediatric ALL does not significantly increase the risk for vincristine‐associated toxicities.…”

“…Second, the prevalence of CIPN has been noted to peak 2–4 months after beginning therapy and recent findings suggest that vincristine‐induced peripheral neuropathy should be recognized as a late effect of chemotherapy Smitherman et al . assessed toxicity during the first 6 weeks of therapy, which is a probably too short of a time frame to see any significant toxicities or dose reductions of vincristine that would be due to the concomitant administration of fluconazole.…”

Reply to: Vincristine toxicity with coadministration of fluconazole long‐term concerns

“…We are grateful to Thackray et al. for their thoughtful consideration of our manuscript examining the risk for vincristine‐induced peripheral neuropathy (VIPN) during induction therapy among children treated for ALL. In their Letter to the Editor, they question the validity of our findings due to methodological concerns regarding the timing for our assessment of VIPN outcomes and our decision not to report rates of fungal infection.…”