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Vincristine-associated Neuropathy With Antifungal Usage: A Kaiser Northern California Experience
Mina Nikanjam1, Aida Sun2, Mark Albers3
1Division of Host-Microbe Systems and Therapeutics, University of California San Diego, San Diego.
Abstract:
The dose-limiting toxicity for vincristine is peripheral neuropathy which can be potentiated with concurrent usage of azole antifungals. The current retrospective study assessed the incidence of concurrent vincristine and azole antifungal usage to determine if it led to increased neurotoxicity for the Kaiser Northern California pediatric acute lymphoblastic leukemia (ALL) and Hodgkin lymphoma patient population. Data were obtained from the electronic medical record (2007 to 2014). In total, 130 subjects received at least one dose of vincristine for ALL or Hodgkin lymphoma (median age 9, 88% ALL, 58% male, 47% Caucasian). Thirty one percent of patients received concurrent antifungal usage (fluconazole, 78%; voriconazole, 10%; fluconazole/voriconazole, 12%); however, concurrent antifungal usage accounted for <15% of vincristine doses. Grade 2 or greater neuropathy occurred in 51% of patients; grade 3 neuropathy was present in 8% of patients. No difference in the incidence of grade 2 or greater neuropathy was observed with the concurrent use of antifungal therapy (P=0.35), sex (P=0.59), type of cancer (P=0.41), ethnicity (P=0.29), or age (P=0.39), but was higher with increasing amount of vincristine doses (P=0.004). These results suggest that concurrent azole antifungal usage with vincristine for patients with ALL and Hodgkin lymphoma was low in the Kaiser Northern California population and limited usage as needed may be reasonable and safe.
Insights
Concurrent azole antifungal use with vincristine in pediatric cancer patients did not increase neurotoxicity. This retrospective study found limited concurrent use was safe, with neuropathy linked to higher vincristine doses, not antifungals.
Area of Science:
- Oncology
- Pharmacology
- Neuroscience
Background:
- Vincristine-induced peripheral neuropathy is a dose-limiting toxicity.
- Azole antifungals may potentiate vincristine neurotoxicity.
- The safety of concurrent use in pediatric cancer patients requires investigation.
Purpose of the Study:
- To assess the incidence of concurrent vincristine and azole antifungal use in pediatric patients with acute lymphoblastic leukemia (ALL) and Hodgkin lymphoma.
- To determine if concurrent antifungal use increases neurotoxicity in this population.
Main Methods:
- Retrospective study of electronic medical records from Kaiser Northern California (2007-2014).
- Identified pediatric patients with ALL or Hodgkin lymphoma receiving vincristine.
- Analyzed incidence of concurrent azole antifungal use and neurotoxicity (Grade 2 or greater neuropathy).
Main Results:
- 31% of patients received concurrent azole antifungals (fluconazole most common).
- Concurrent antifungal use did not significantly increase the incidence of Grade 2 or greater neuropathy (P=0.35).
- Higher vincristine doses were associated with increased neuropathy risk (P=0.004).
Conclusions:
- Concurrent azole antifungal use with vincristine was infrequent in this pediatric population.
- Limited, as-needed concurrent use of azole antifungals with vincristine appears safe.
- Vincristine dose, not concurrent azole antifungal use, was the primary driver of neurotoxicity.
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