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Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer.

ABSTRACT: BACKGROUND:Vincristine is an integral treatment component of many childhood tumors with potentially dose-limiting sensory and/or motor neuropathy. Results from a pilot study on the incidence of vincristine-induced peripheral neuropathy (VIPN) as well as the efficacy and safety of glutamine in reducing signs and symptoms of VIPN in children with cancer are presented. METHODS:Fifty-six patients between the ages of 5-21 with newly diagnosed leukemia, lymphoma, extracranial solid tumor or medulloblastoma and expected to receive a minimum cumulative dose of 6 mg/m2 of vincristine over a 30-week period were eligible. Patients' neurological functioning was monitored every 3 weeks using clinical history, exam, and assessment of motor functioning. Upon identification of neuropathy, patients were randomized to either glutamine (6 g/m2 per dose twice daily, maximum 10 g/dose) or placebo for a 3-week period followed by 3-week wash out period (Time 3). RESULTS:Forty-nine patients were fully evaluable and 100 % developed neuropathy per study definitions. No significant differences in demographics or side effects were noted between the randomized groups. The distribution of sensory neuropathy scores between the two groups was statistically significant after the intervention (p = 0.022). Children receiving glutamine also rated their quality of life (QoL) as 8.42 points higher on the PedsQL total score than those receiving placebo (p = 0.031). CONCLUSIONS:Glutamine supplementation is well tolerated and associated with improvements in sensory function and self-reported overall quality of life. Future studies are warranted to confirm the efficacy of glutamine for the treatment of vincristine-related sensory neuropathy in pediatric cancer patients.

SUBMITTER: Sands S

PROVIDER: S-EPMC5598352 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer.

Sands Stephen S Ladas Elena J EJ Kelly Kara M KM Weiner Michael M Lin Meiko M Ndao Deborah Hughes DH Dave Amie A Vahdat Linda T LT Bender Julia Glade JG

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 20161109 3

<h4>Background</h4>Vincristine is an integral treatment component of many childhood tumors with potentially dose-limiting sensory and/or motor neuropathy. Results from a pilot study on the incidence of vincristine-induced peripheral neuropathy (VIPN) as well as the efficacy and safety of glutamine in reducing signs and symptoms of VIPN in children with cancer are presented.<h4>Methods</h4>Fifty-six patients between the ages of 5-21 with newly diagnosed leukemia, lymphoma, extracranial solid tumo ...[more]

PMID: 27830395

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Project description:Simple Summary Vincristine is a type of chemotherapy that is often used in the treatment of children with cancer. The main side effect of vincristine is nerve damage. Patients experience symptoms such as tingling, pain or muscle weakness. Some children are more sensitive to vincristine than others, which may depend on variations in genes and in the breakdown of vincristine by the body. In this study, we investigated the effect of variations in genes on nerve damage due to vincristine and breakdown of vincristine by the body. We found that nine variations in seven genes were associated with nerve damage due to vincristine, whereas three variations in three genes were associated with the breakdown of vincristine by the body. It is important that future studies try to replicate these findings. Our findings help us towards the goal of tailoring vincristine treatment to each child, with optimal therapeutic effect while limiting nerve damage. Abstract Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occasions at multiple time points. A linear two-compartment model with first-order elimination was used, and targeted next-generation DNA sequencing was performed. Genotype–trait associations were analyzed using mixed-effect models or logistic regression analysis for repeated measures, or Poisson regression analysis in which the highest VIPN score per patient was included. Nine single-nucleotide polymorphisms (SNPs) in seven genes (NDRG1, GARS, FIG4, FGD4, SEPTIN9, CEP72, and ETAA1) were associated with VIPN. Furthermore, three SNPs in three genes (MTNR1B, RAB7A and SNU13) were associated with PK of VCR. In conclusion, PK of VCR and VIPN are influenced by SNPs; upfront identification of those that lead to an altered susceptibility to VIPN or VCR exposure could help individualize VCR treatment.

Dataset Information

Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer.

Publications

Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer.

Similar Datasets

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