Vincristine-associated Neuropathy With Antifungal Usage: A Kaiser Northern California Experience

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.

Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review

“…Thus, coadministration of vincristine and itraconazole decreases the metabolism of vincristine to a greater extent than coadministration with fluconazole, causing notably enhanced neurotoxicity. Consistently, three studies did not observe significant differences in neuropathy upon fluconazole treatment [69, 71, 73], whereas six independent studies report higher incidence and severe neuropathy upon itraconazole treatment [1, 70, 72, 74–76] (Table 3).…”

Population Pharmacokinetics of Vincristine Related to Infusion Duration and Peripheral Neuropathy in Pediatric Oncology Patients

“…It has been previously reported that azole antifungal treatment concurrent with VCR dosing influences the development of VIPN [ 22 , 23 , 24 ]. However, our study does not show any relationship between VCR PK and azole treatment.…”

“…In addition, a drug–drug interaction between VCR and concurrent treatment with many azole antifungals was previously reported [ 22 , 23 , 24 ]. These azole antifungals are frequently used during intensive chemotherapeutic treatment in children for the prevention or treatment of invasive fungal infections [ 25 ].…”

Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment

“…As said before, vincristine is metabolized by CYP3A4 in the liver. In pediatric patients, it is frequently described as the association between VIPN and concomitant interacting treatments with CYP3A4 inhibitors [ 59 ]. The azole antifungals are strong CYP3A4 inhibitors and neurotoxic themselves, even in the absence of other neurotoxic chemotherapy; consequently they should be avoided during vincristine regimens [ 60 , 61 ].…”