Tracing the incidence of paclitaxel-induced peripheral neuropathy (2009)

I read with great interest the recently published paper in your distinguished journal by Loven et al. (2009), on the insignificant effect of oral glutamine in preventing paclitaxel-induced peripheral neuropathy (PIPN). PIPN is widely acknowledged as a major and potentially dose-limiting adverse event of paclitaxel-based chemotherapy, with incidence rates ranging between 25% and 70% (Argyriou et al. 2007). To address the important clinical issue of PIPN protection, Loven et al. (2009) conducted an otherwise well-designed randomised placebo-controlled trial, using oral glutamate. To my opinion however, the reliability of their results is limited from a significant methodological drawback. Authors evaluated the effect of glutamine administration on the incidence of PIPN using a self-invented instrument, termed as ‘severity score’. The severity score of a symptom was arbitrarily considered as the increment in its grade of toxicity as measured pre-treatment evaluation compared with post-treatment follow up. Despite the different comprehensive neurotoxicity scales used thus far to assess PIPN, its accurate tracing of incidence and grading still represents an unsolved issue (Postma & Heimans. 2000; Argyriou et al. 2008). Validity and reliability are considered the minimum requirements for outcome measures prior to their use in assessing any particular medical condition. Outcome measures need to be clinimetrically well evaluated, meeting the demands of being simple, valid, reliable and responsive (Hobart et al. 1996). I strongly support the view that that the monitoring of PIPN should be performed using a valid, reliable and composite measure that includes symptoms, signs, ability aspects and where available electrophysiological measures. In line this view, Loven et al. (2009) assessed the effect of glutamate on the incidence of PIPN, using clinical and electrophysiological examination. However, the results of these examinations were not summarised by means of a valid grading scale, thereby significantly degrading their reliability. As authors acknowledge, the limited number of patients possibly lacked the statistical power to detect statistically significant differences in outcome measures. Use of a valid and reliable grading instrument would possibly allow the decrease in the number of patients needed in randomised controlled trials (van Doorn & Merkies 2008) and would as well have possibly facilitated the discovery of a beneficial effect of glutamate in preventing PIPN in the Loven et al. (2009) randomised placebo-controlled trial. Overall, with this letter to the editor I would like to bolster the argument that the identification of a proper and validated outcome measure will allow the design of clinical trials, reliably assessing the prophylactic efficacy of drugs in the clinical setting. The Total Neuropathy Score fulfils these conditions and to my opinion should be implemented so as to asses the extent of peripheral nerve damage secondary to paclitaxel-based chemotherapy. Total Neuropathy Score has been recently found reliable and valid in the assessment of chemotherapy-induced peripheral neuropathy, including the neurotoxicity secondary to paclitaxel-based chemotherapy (Cavaletti et al. 2007).