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

Thackray, Jennifer; Spatz, Krisoula; Steinherz, Peter G.

doi:10.1002/pbc.26652

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…Interestingly, most of these patients received fluconazole. Even though a higher incidence and severe neuropathy were reported upon treatment with other members of the azole family [7], our results agree with others in that the judicious use of azole antifungals is warranted in vincristine-treated patients, as the risk of neuropathy remains with fluconazole, even when it is used at the therapeutic dose [34]. With respect to the clinical parameters, an elevated level of WBCs was found in adults with neuropathy, which was not observed in pediatric patients.…”

Section: Vincristine-induced Neuropathy In Adult Patientssupporting

confidence: 84%

Vincristine-Induced Neuropathy in Patients Diagnosed with Solid and Hematological Malignancies: The Role of Dose Rounding

Alwhaibi,

Alshamrani,

Alenazi

et al. 2023

JCM

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Background: Vincristine is a vital constituent of chemotherapeutic regimens. Vincristine-induced neuropathy is a challenging adverse effect that impacts quality of life and treatment course. The dose rounding of chemotherapies is a strategy that is commonly used in clinical practice. Nevertheless, the frequency of developed neuropathy in vincristine first-time users and the potential association with dose rounding remains elusive. Methods: A retrospective analysis was conducted on patients administered vincristine for the first time between 2016 and 2022 using the King Saud University Medical City (KSUMC) database. Patients were stratified into pediatric and adult groups. Neuropathy frequency, its association with demographic and clinical parameters, and the Impact of dose rounding were assessed using SPSS software version 28. Results: Approximately 34.6% of patients were diagnosed with neuropathy after vincristine administration. Autonomic neuropathy was common among affected adults and pediatric patients (55.1% and 56.1%, respectively), while cranial neuropathy was more frequent in pediatric patients. Higher BSA (p = 0.038) and Scr (p = 0.044) in the pediatric group, the presence of respiratory comorbidities (p = 0.044), and the use of azole antifungals (p < 0.001) in the adult group were significantly associated with neuropathy episodes. The rounding-up of vincristine doses was significantly associated with increased neuropathy occurrence (p < 0.001), while dose rounding-down was significantly associated with a decrease in neuropathy in both groups of patients (p < 0.001). Conclusions: Our findings demonstrate that autonomic neuropathy is the most common vincristine-related neuropathy, regardless of the patient’s age. Dose rounding is a significant determinant of vincristine-induced neuropathy in both groups. Further studies are needed to evaluate the variables that exacerbate or prevent neuropathy associated with the first-time use of vincristine.

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Section: Vincristine-induced Neuropathy In Adult Patientssupporting

confidence: 84%

Vincristine-Induced Neuropathy in Patients Diagnosed with Solid and Hematological Malignancies: The Role of Dose Rounding

Alwhaibi,

Alshamrani,

Alenazi

et al. 2023

JCM

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“…Fluconazole seems to be safer than other azoles when administered in association with vincristine, especially when used as antifungal prophylaxis. Fluconazole has a dose-dependent effect on the CYP450 enzyme system, so the risk of neurotoxicity is more consistent when used at the therapeutic dose [ 62 ].…”

Section: Treatment-related Risk Factors For Vipnmentioning

confidence: 99%

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

Triarico

Romano

Attinà

et al. 2021

IJMS

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Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. Neuropathy may be sensory, motor and/or autonomic, with consequent reduction, delay or discontinuation of vincristine-chemotherapy, but also pain, disability, reduced quality of life of patients and an increase in medical costs. Vincristine acts out its antineoplastic function by altering the normal assembly and disassembly of microtubules, with their consequent mitosis block and death. Vincristine leads to VIPN through a complex mechanism of damage, which occurs not only on the microtubules, but also on the endothelium and the mitochondria of nerve cells. Furthermore, both patient-related risk factors (age, race, ethnicity and genetic polymorphisms) and treatment-related risk factors (dose, time of infusion and drug–drug interactions) are involved in the pathogenesis of VIPN. There is a lack of consensus about the prophylaxis and treatment of VIPN among pediatric oncologic patients, despite several molecules (such as gabapentin, pyridoxine and pyridostigmine, glutamic acid and glutamine) having been already investigated in clinical trials. This review describes the molecular mechanisms of VIPN and analyzes the risk factors and the principal drugs adopted for the prophylaxis and treatment of VIPN in pediatric patients with cancer.

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“…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. While they raise important points for discussion, we disagree that these concerns negate the validity and clinical applicability of this work.…”

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confidence: 94%

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

Smitherman

Faircloth

Gold

2017

Pediatric Blood & Cancer

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

Cited by 4 publications

References 9 publications

Vincristine-Induced Neuropathy in Patients Diagnosed with Solid and Hematological Malignancies: The Role of Dose Rounding

Vincristine-Induced Neuropathy in Patients Diagnosed with Solid and Hematological Malignancies: The Role of Dose Rounding

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

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

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