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Abstract
Aims Vincristine is a vinca alkaloid which is used as a chemotherapeutic agent for multiple paediatric haematological and solid tumours. This is frequently complicated by dose-dependent neurological toxicity. Studies suggest that polymorphisms of the CYP3A and ABCB1 genes contribute to vincristine-related neurotoxicity, which may explain variation in the prevalence of this side effect and overall prognosis. An established link between mercaptopurine toxicities and polymorphisms led to the incorporation of targeted genetic screening into therapy, suggesting a potential for tailored vincristine treatment. We aim to identify cases of vincristine-related neurotoxicity within our patient population, characterise trends in these toxicities and investigate any demographic influence on these side effects.
Methods This five year retrospective study from December 2008 to February 2014 focused on paediatric patients presenting to our oncology unit who were undergoing first line chemotherapy for Acute Lymphoblastic Leukaemia, Low Grade Glioma and Wilms Tumour. These malignancies were chosen as they had a heavy burden of vincristine in their treatment protocols. Neurotoxicity was assessed using the Common Terminology Criteria of Adverse Events (CTCAE) (Table 1). Patient records were studied for details of neurotoxicity using this tool and any changes that were made to their dosage of vincristine in their treatment plan as a result.
Common toxicity criteria for adverse events
Institute NC. Common Terminology Criteria for Adverse Events (CTCAE): Redesign and Life Cycle Management Version 4 ed. 2010
Results Frequency: There were 66 “neurotoxic events” (Figure 1). A high incidence of neurotoxic events of grade 1–3 severity was found with 71% of patients experiencing one or more events. Motor neurotoxicity was the modal group. Demographic: Toxicity was higher amongst females and the older age categories. There was an ethnic variation of trend toward increased toxicity. There was no clear relationship between tumour type and neurotoxicity. Timing: Two thirds of all neuropathies occurred within the first three months (Figure 2).
Neurotoxic events divided by type and grade of event. Sample size n=63. *Autonomic: all events revorded were constipation
Time between commencement of chemotherapy and development of neurotoxicity
Conclusion This pilot study demonstrates a high rate of vincristine-related neurotoxicity within a subset of the paediatric haematology and oncology population, warranting a larger study and potential pharmacogenetic analysis.