THalidomide sensory neurotoxicity: results of a collaborative clinical and neurophysiolgical study

Abstract

Despite long‐lasting use, several features of thalidomide neurotoxicity have yet to be resolved. A more detailed knowledge of thalidomide‐induced sensory neurotoxicity is desirable, particularly in view of the future use of thalidomide derivatives which are currently under investigation. Our study demonstrates that thalidomide sensory neurotoxicity is cumulative dose‐dependent, but this effect is evident only when the dose is relatively high (in our study >20 g). In fact, the risk of developing sensory neuropathy is low (around 10%) below this threshold, while it steadily increases with increasing cumulative doses. In our series, a discrepancy between clinical and neurophysiological results was frequent when a low cumulative dose of thalidomide was administered. Regarding the need for thalidomide withdrawal at the onset of any evidence of peripheral neuropathy, we followed up the course of seven patients who were clinically and neurophysiologically normal at baseline, but had treatment‐induced neurotoxicity and a very severe change in their SAPs. In all these cases the thalidomide dose was reduced and no clinically‐relevant worsening was observed despite a further marked reduction in their SAPs. This finding suggests that thalidomide withdrawal is not mandatory even in the presence of marked abnormalities in sensory neurophysiological parameters, provided that an accurate clinical follow‐up is guaranteed and the dose is adjusted.