Severe encephalopathy and polyneuropathy induced by dichloroacetate

Abstract

Dear Sirs,In 2007, an article in the New Scientist presented dichlo-roacetate (DCA) as ‘a cheap and safe drug that kills mostcancers’ [1]. This statement was based on the findings ofBonnet et al. (2007) [2], who showed that DCA inducesapoptosis and decreases in vitro tumor growth in severalcancer cell lines by shifting the metabolism of cancer cellsfrom glycolysis to glucose oxidation. In the same study,DCA was administered to nude rats in the drinking water(75 mg/L, during 3 months) and could prevent and reversetumor growth without apparent toxicity. Dichloroacetatewas proposed as an attractive candidate for proapoptoticcancer therapy [3]. Without any clinical data, DCA washailed as a ‘miracle drug’ on internet-based patient forumsand has since been prescribed off-label by alternativephysicians or bought directly by patients via webshops(http://www.puredca.com and http://www.pharma-dca.com).Recently, a small clinical study was performed in fiveglioblastoma patients treated with various DCA doses.Grade II and grade III polyneuropathy occurred in patientstreated with DCA 25 mg/kg/day and 50 mg/kg/day,respectively. The maximum DCA dose at which none ofthe patients had a clinically significant peripheral neurop-athy was 6.25 mg/kg orally, twice a day (12.5 mg/kg/day)for at least 3 months [4]. For the first time, we present apatient who developed encephalopathy and grade III sen-sorimotor polyneuropathy after 4 weeks of DCA treatment(15 mg/kg/day).A 46-year old patient with melanoma which hadmetastasized to the lung and lymph nodes 2 years previ-ously, was admitted to the Antoni van LeeuwenhoekHospital in The Netherlands because of confusion and gaitdisturbance. Four weeks before admission he had startedtaking capsules with identified DCA (400 mg, thrice daily,corresponding with 15 mg/kg/day) and vitamin A capsules(150,000 IU/day), prescribed by an alternative physician.On neurological examination he showed impaired mentalprocessing, dysarthria and an unsteady gait. MRI of thebrain and serum blood tests were normal. In the followingdays he became more confused, showed aggressivebehaviour, had visual hallucinations and dysphasia. Cere-brospinal fluid (CSF) examination demonstrated normalbiochemical parameters, no malignant cells and negativePCRs for neurotrophic viruses. Antineuronal antibodyscreening was negative. Both the DCA and vitamin Acapsules were stopped on the day of admission. The DCAconcentration in the CSF on day 2 after hospital admissionwas 78 lg/mL, as measured by liquid chromatographytandem mass-spectrometry. On day 16, the DCA CSFconcentration decreased to 11 lg/mL, indicating an elim-ination half-life for DCA in the CSF of approximately5 days. No serum samples for DCA measurement wereavailable.