Risk Factors for Early-Onset Peripheral Neuropathy Caused by Vincristine in Patients With a First Administration of R-CHOP or R-CHOP-Like Chemotherapy

Abstract

BackgroundPeripheral neuropathy is a well-known side effect of vincristine (VCR), a microtubule inhibitor used for R-CHOP or R-CHOP-like (namely R-CVP and R-THP-COP) regimens. Previous studies have shown that both the total dose of VCR and the number of treatment cycles are related to the incidence of VCR-induced peripheral neuropathy (VIPN). However, VIPN will also occur during the first treatment cycle regardless of the total dose of VCR or number of treatment cycles (early-onset VIPN). There is little information about early-onset VIPN, and it is difficult to predict. The present study’s goal was to identify risk factors for early-onset VIPN.MethodsWe analyzed the case records of patients who had their first administration of an R-CHOP or R-CHOP-like regimen between April 2008 and August 2013 at Tokushima University Hospital in Tokushima, Japan. To identify the risk factors for early-onset VIPN, we performed univariate and multivariate logistic regression analyses.ResultsForty-one patients underwent an R-CHOP or R-CHOP-like regimen for the first time at Tokushima University Hospital between April 2008 and August 2013, and 14 patients had grade 1 or higher early-onset VIPN. A univariate analysis revealed that age, the dose of VCR and the concomitant use of aprepitant appeared to be the risk factors of early-onset VIPN. In our calculation using receiver-operator characteristics curves, the cut-off value for patient age was 65 years and that of the dose of VCR was 1.9 mg. A multivariate analysis revealed that VCR dose ≥ 1.9 mg and the concomitant use of the antiemetic aprepitant were independent risk factors for early-onset VIPN.ConclusionsOur present study showed that the patients who had VCR dose ≥ 1.9 mg and the concomitant use of aprepitant had the risk for early-onset VIPN. This suggests that it is important to use aprepitant in light of the risk of early-onset VIPN and the benefit of aprepitant’s antiemetic effect in R-CHOP and R-CHOP-like regimens.

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

“…Statistically significant differences in peripheral neuropathy were not noted between 103 patients with hyperglycemia and the 175 patients without; furthermore, a subanalysis of patients with previously diagnosed diabetes or elevated baseline blood glucose did not reveal any differences. Consistently, no difference in neuropathy incidence was found when comparing diabetic patients requiring diabetic medications with nondiabetic patients [54].…”

“…1). Of these articles, 13 investigated VIN measuring methods [9, 32–43], while 11 records investigated clinical risk predictors for VIN development [44–54]. Fifteen records studied molecular risk parameters [5, 55–68].…”

“…Furthermore, several studies report advanced age in pediatric patients as a clinical risk factor [61, 69, 73]. However, some studies do not find this correlation in pediatric or adult patients [44, 49] and others even suggest the opposite for both groups [54, 88, 95].…”

Vinca alkaloids, thalidomide and eribulin‐induced peripheral neurotoxicity: From pathogenesis to treatment

“…The median time to peripheral nerve damage onset was 37 days; but had a notable wide range of appearance from 0 up to 171 days, supporting as such the view that VIPN might occur after administering the first vincristine treatment cycle regardless of its total delivered dose . A vincristine dose of ≥1.9 mg and the concomitant use of the antiemetic aprepitant were found in another study to independently predict the installation of early‐onset VIPN …”

“…Advanced age seems to have an adverse influence in determining the severity of CIPN . Younger children tolerate relatively higher dosage of vincristine and develop less severe VIPN compared to adolescents and adults .…”