Transient Hepatotoxicity Induced by Vinblastine in a Young Girl with Chiasmatic Low Grade Glioma

Author(s): Niels E. Franke*, Geert Jan Blok, Marsha L. Voll, Antoinette Y.N. Schouten-van Meeteren

Journal Name: Current Drug Safety

Volume 15 , Issue 3 , 2020

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Graphical Abstract:


Background: Vinblastine (VBL) is a cytostatic drug frequently applied in children with lymphoma and progressive low-grade glioma (LGG), with hematotoxicity as the main side effect.

Case Report: Here, the case of a 7-month-old girl with tumor progression of an LGG during standard chemotherapy with carboplatin and vincristine, is presented. Switching to VBL led to a 20-30- fold increase of transaminases (grade IV CTCAE 5.0), spontaneously resolving after the end of treatment. The toxicity is possibly age-related since it did not re-occur at the restart of VBL at 4 years old. This finding might have consequences for toxicity screening in future protocols, especially when including infants.

Keywords: Vinblastine, hepatotoxicity, CTCAE, low-grade glioma, infant, chiasmatic.

Ostrom MAQT, Gittleman HM, de Blank PM, Finlay MBJL, Gurney JG, McKean-Cowdin R, et al. American brain tumor association adolescent and young adult primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Available from:
Ostrom QT, De Blank PM, Kruchko C, et al. Alex’s lemonade stand foundation infant and childhood primary brain and central nervous system tumors diagnosed in the United States in 2007- 2011. Available from:
Gnekow AK, Kandels D, Tilburg CV, et al. SIOP-E-BTG and GPOH guidelines for diagnosis and treatment of children and adolescents with low grade glioma. Klin Padiatr 2019; 231(3): 107-35.
[] [PMID: 31108561]
Ripperger T, Bielack SS, Borkhardt A, et al. Childhood cancer predisposition syndromes-A concise review and recommendations by the cancer predisposition working group of the society for pediatric oncology and hematology. Am J Med Genet A 2017; 173(4): 1017-37.
[] [PMID: 28168833]
Bouffet E, Jakacki R, Goldman S, et al. Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol 2012; 30(12): 1358-63.
[] [PMID: 22393086]
Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, et al. Erratum: Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 2006; 116(10): 2827.
Bijman MNA, van Nieuw Amerongen GP, Laurens N, van Hinsbergh VWM, Boven E. Microtubule-targeting agents inhibit angiogenesis at subtoxic concentrations, a process associated with inhibition of Rac1 and Cdc42 activity and changes in the endothelial cytoskeleton. Mol Cancer Ther 2006; 5(9): 2348-57.
[] [PMID: 16985069]
Roussel Uclaf Causality Assessment Method (RUCAM) in drug induced liver injury - LiverTox - NCBI Bookshelf. Available from:
Triptorelin. LiverTox: Clinical and Research Information on Drug- Induced Liver Injury 2012. Available from:
European Medicines Agency (EMA). Benzyl alcohol and benzoic acid group used as excipients 2017. 1-16. Available from:
Gershanik J, Boecler B, Ensley H, McCloskey S, George W. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med 1982; 307(22): 1384-8.
[] [PMID: 7133084]
Brown WJ, Buist NRM, Gipson HT, Huston RK, Kennaway NG. Fatal benzyl alcohol poisoning in a neonatal intensive care unit. Lancet 1982; 1(8283): 1250.
[] [PMID: 6123006]
Cronin CM, Brown DR, Ahdab-Barmada M. Risk factors associated with kernicterus in the newborn infant: importance of benzyl alcohol exposure. Am J Perinatol 1991; 8(2): 80-5.
[] [PMID: 2006946]
Lafay-Cousin L, Holm S, Qaddoumi I, et al. Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction. Cancer 2005; 103(12): 2636-42.
[] [PMID: 15861409]
Lassaletta A, Scheinemann K, Zelcer SM, et al. Phase II weekly vinblastine for chemotherapy-naïve children with progressive low-grade glioma: A Canadian pediatric brain tumor consortium study. J Clin Oncol 2016; 34(29): 3537-43.
[] [PMID: 27573663]
Verschuur A, Heng-Maillard M-A, Dory-Lautrec P, et al. Metronomic four-drug regimen has anti-tumor activity in pediatric low-grade glioma; The results of a phase II clinical trial. Front Pharmacol 2018; 9(9): 950.
[] [PMID: 30319400]
Spiller M, Marson P, Perilongo G, Farina M, Carli M, Bisogno G. A case of vinblastine overdose managed with plasma exchange. Pediatr Blood Cancer 2005; 45(3): 344-6.
[] [PMID: 15602712]
Aversa SML, Zanon S, Marino D, Canova F, Chiarion-Sileni V, Jirillo A. Overdose of vinblastine in place of vinorelbine during IGEV chemotherapy. Immunopharmacol Immunotoxicol 2012; 34(5): 879-80.
[] [PMID: 22390365]
Zhou XJ, Martin M, Placidi M, Cano JP, Rahmani R. In vivo and in vitro pharmacokinetics and metabolism of vincaalkaloids in rat. II. Vinblastine and vincristine. Eur J Drug Metab Pharmacokinet 1990; 15(4): 323-32.
[] [PMID: 2088769]
van Tellingen O, Beijnen JH, Nooijen WJ, Bult A. Tissue disposition, excretion and metabolism of vinblastine in mice as determined by high-performance liquid chromatography. Cancer Chemother Pharmacol 1993; 32(4): 286-92.
[] [PMID: 8324870]
Chagas CM, Alisaraie L. Metabolites of vinca alkaloid vinblastine: tubulin binding and activation of nausea-associated receptors. ACS Omega 2019; 4(6): 9784-99.
[] [PMID: 31460070]
de Wildt SN, Kearns GL, Leeder JS, van den Anker JN. Cytochrome P450 3A: ontogeny and drug disposition. Clin Pharmacokinet 1999; 37(6): 485-505.
[] [PMID: 10628899]
Noureddin N, Kaplowitz N. Overview of mechanisms of drug-induced liver injury (DILI) and key challenges in DILI research Methods in pharmacology and toxicology. Humana Press Inc. 2018; pp. 3-18.
Welch MA, Köck K, Urban TJ, Brouwer KLR, Swaan PW. Toward predicting drug-induced liver injury: parallel computational approaches to identify multidrug resistance protein 4 and bile salt export pump inhibitors. Drug Metab Dispos 2015; 43(5): 725-34.
[] [PMID: 25735837]
Gebhardt R. Disappearance of visible bile canaliculi caused by vinblastine in primary cultures of rat hepatocytes. Exp Cell Res 1983; 144(1): 218-23.
[] [PMID: 6840206]
Mirow C, Pietsch T, Berkefeld S, et al. Children <1 year show an inferior outcome when treated according to the traditional LGG treatment strategy: a report from the German multicenter trial HIT-LGG 1996 for children with low grade glioma (LGG). Pediatr Blood Cancer 2014; 61(3): 457-63.
[] [PMID: 24039013]

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Article Details

Year: 2020
Published on: 17 November, 2020
Page: [231 - 235]
Pages: 5
DOI: 10.2174/1574886315666200719013523
Price: $65

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