Abstract
BackgroundFluoroquinolone antibiotics are frequently utilized in pediatric oncology patients as prophylaxis or step‐down therapy following broad spectrum beta‐lactam therapy for febrile neutropenia. Concerns regarding neurotoxicity limit the use of these agents. No studies have evaluated the association between fluoroquinolone use and neurotoxicity in pediatric oncology patients receiving other neurotoxic agents such as vincristine.MethodsAn observational cohort study comprising patients aged 0‐18 at diagnosis enrolled on a prospective study for treatment of acute lymphoblastic leukemia (ALL) at a pediatric comprehensive cancer center between October 2007 and November 2018. Data for neuropathic pain and sensory or motor neuropathy were collected prospectively, and a Cox proportional hazards regression model was used to evaluate associations between administration of fluoroquinolone antibiotics during induction therapy and subsequent development of vincristine‐induced peripheral neurotoxicity (VIPN).ResultsA total of 598 participants were enrolled, including 338 (57%) who received fluoroquinolones during induction therapy; of these 470 (79%) were diagnosed with VIPN and 139 (23%) were diagnosed with high‐grade (Grade 3+) VIPN. On unadjusted analyses, and analyses adjusted for age and race, there was no evidence of an association between fluoroquinolone exposure and subsequent VIPN (hazard ratio [HR] 0.8, 95% CI 0.5‐1.04, P = .08) or high‐grade VIPN (HR 1.1, 95% CI 0.4‐2.2, P = .87).ConclusionsThe results of this observational study do not show an association between exposure to fluoroquinolone antibiotics during induction therapy for ALL and subsequent development of vincristine‐induced peripheral neuropathies, and suggest that a large increase in VIPN is unlikely.
Highlights
Because levofloxacin was used with higher frequency than ciprofloxacin, we aimed to evaluate the potential effect of levofloxacin by comparing the relative effect of ciprofloxacin vs levofloxacin, and no fluoroquinolone vs levofloxacin, on neuropathic pain or neuropathy using Cox proportional hazard regression models as described above
Neuropathy and neuropathic pain were significantly associated with age at diagnosis >6 years and white race, but not with sex, or leukemia risk category. (Table S2) race and age were included as covariates in adjusted models
In unadjusted Cox proportional hazards regression models, exposure to fluoroquinolone antibiotics during induction therapy was not associated with an increase in neuropathic pain, neuropathy, combined pain/neuropathy, or high-grade neuropathy or neuropathic pain. (P = .066, hazard ratio [HR], 95% confidence interval [95% CI] 0.52-1.02; P = .852, HR 0.92, 95% CI 0.39-2.18; P = .084, HR 0.75, 95% CI 0.54-1.04; P = .872, HR 1.06, 95% CI 0.51-2.22, respectively)
Summary
Fluoroquinolone antibiotics are known to be neurotoxic, causing a 1.5-2-fold increase in risk of peripheral neuropathy in adults Whether such neurotoxicity occurs in children receiving other neurotoxic agents is unknown. No studies have evaluated the association between fluoroquinolone use and neurotoxicity in pediatric oncology patients receiving other neurotoxic agents such as vincristine. Data for neuropathic pain and sensory or motor neuropathy were collected prospectively, and a Cox proportional hazards regression model was used to evaluate associations between administration of fluoroquinolone antibiotics during induction therapy and subsequent development of vincristine-induced peripheral neurotoxicity (VIPN). Conclusions: The results of this observational study do not show an association between exposure to fluoroquinolone antibiotics during induction therapy for ALL and subsequent development of vincristine-induced peripheral neuropathies, and suggest that a large increase in VIPN is unlikely
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