Monday, 3 May 2010

Vincristine Neurotoxicity and Malnutrition

Vincristine is an important weapon in the chemotherapeutic arsenal against several childhood cancers including acute lymphoblastic leukaemia, lymphomas, Wilm's tumour and various brain tumours. It does have side-effects, notable neurotoxicity which manifests in various ways. It is accepted that malnutrition (more common in resource-poor nations) can exacerbate vincristine-related neurotoxicity.

A report from Delhi highlights the prevalence of vincristine-related neurotoxicity (at dose of 1.4 mg/m2) which was seen in 10 out ot 20 children with various cancers treated over a two year period (Ref - Gomber et al, Indian J Pediatrics, Jan 2010). This is much higher than that reported from resource-rich nations. In 6 cases, the severity of the toxicity warranted temporary discontinuation of the drug. The weight of all patients who developed neurotoxicity was below the 3rd centile for age and was significantly lower than those children who did not develop neurotoxicty.

Clues to the mechanism by which malnutrition can increase vincristine-related neurotoxicity can be found in another recent paper (ref - Israel et al, European Journal of Cancer, 2010). The pharmacockinetics of vincristine (at dose of 1.5 mg/m2) were studied in 11 children with Wilm's tumour from Malawi and 8 children from UK. The children from Malawi had significantly lower weight-for-height than those in UK. The clearence of vincristine was significantly slower in Malawian children and as a result the exposure to vincristine (measured by area under the curve) was almost two times longer. There was a linear corelation between the extent of malnutrition and the area under the curve for vincristine.

The above two studies would suggest that in children with cancer who are malnourished, we may have to reconsider the dose of vincristine. Clearly, this area merits more research in India and in other resource-poor settings.

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