artemisinin derived drugs are available for the treatment of malaria. Except for two case reports, no major side effects have been reported in humans at doses used for the treatment of malaria but it is still unknown whether the higher doses required for the treatment of cancer patients could cause major side effects. In vivo studies showed that doses of artemisinin-related endoperoxides of at least 5 times higher than those used for antimalaria therapy are required in order to induce an effect. The safety of such doses has not yet been evaluated in Phase I clinical trials.
A first case report describes a boy who received artesunate suppositories and died 13 days.25 He had received a dose 7-fold higher than the maximum recommended dose which reportedly led to toxicity of the brain stem.
In a second case report a woman with recently resected early breast carcinoma described symptoms of toxic brainstem encephalopathy.26 Since this neurotoxicity has also been seen in animals, the authors of the case report ascribe the toxicity to artemisinin consumption, although she received also chemotherapy and a mixture of other herbs on top.
On the other hand, a review of the toxicity of artemisinin derivatives suggested that the toxicity seen in laboratory animals does not necessarily occur in humans due to the differences in pharmacokinetic profile after different routes of administration. The oral administration used in humans is unlikely to cause the neurotoxicity seen after intramuscular administration in mice.27,28