Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukemia

Abstract

10049 Background: Vincristine is one of the corner stitches in the treatment of children with acute lymphoblastic leukemia (ALL). Constipation and other peripheral and central neurotoxicities are the most common side effects. Drugs interfering with the metabolism of vincristine might potentiate these side effects. A group of drugs that interact with the metabolism of vincristine are azoles. Several case reports suggest that co-administration of azoles and vincristine lead to increased toxicity. A comparative study exploring toxicity in patients receiving vincristine with and without azoles, is lacking. For this reason, we retrospectively analyzed neurotoxicity induced by vincristine with (n = 20) and without (n = 20) co-administration of azoles in the same patient group. Methods: In total, twenty pediatric patients with de novo ALL were included in this study. Vincristine toxicity was graded retrospectively according to the National Cancer Institute toxicity scale without information considering comedication. Statistical analysis was performed using the Wilcoxon Signed Rank test and McNemar test. Results: Patients receiving vincristine in combination with prophylactic azole treatment experienced significantly more complaints of constipation and peripheral neurotoxicity (P = 0.001 and P< 0.001, respectively). Three patients (15%) treated with azole therapy developed severe toxicity and needed treatment at the pediatric intensive care unit. Vincristine induced CNS toxicity (convulsions, toxic encephalopathy and SIADH) was seen in 6 patients (30%). All these patients were treated with vincristine in combination with an azole. CNS toxicity was not observed in patients receiving vincristine alone (P = 0 .014). Because of severe toxicities, vincristine treatment was significantly reduced (50% of normal dose) in several patients. Conclusions: This study shows that vincristine toxicity is significantly increased when combined with azole treatment and even can be life threatening. Therefore we advise to avoid the combination of azole and vincristine treatment in patients with ALL. No significant financial relationships to disclose.