Bianchi, G., Vitali, A., Caraceni, A., Ravaglia, S., Capri, G., Cundari, S., . . . Gianni, L. (2005). Symptomatic and neurophysiological responses of paclitaxel or cisplatin-induced neuropathy to oral acetyl-L-carnitine. European Journal of Cancer, 41(12), 1746–1750.

Oral acetyl L-carnitine (ALC) was given at 1 g three times per day for eight weeks.

• The total samples consisted of 25 patients (3 men and 22 women) with a mean age of 53 years.
• The patients had grade 3 or greater neuropathy (based on the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI-CTCAE]) during paclitaxel or cisplatin therapy or grade 2 or greater persistent neuropathy after three months of therapy discontinuance.
• Exclusion criteria included having diabetes mellitus and neuropathy from origins other than paclitaxel or cisplatin.

The study had a non-randomized clinical trial design.

• Physical and neurologic examinations were conducted before and after ALC administration by an independent neurologist using the NCI-CTCAE grading scale.
• Conduction velocity of sensory and motor fibers was measured by electromyography.
• Neuropathy was measured by the Total Neuropathy Score (TNS), with each variable scored on a scale of 0 (none) to 4 (severe), and the sum of these forms the TNS.
• For a general neurologic evaluation, patients were evaluated for bulbar symptoms of muscle weakness sensory disturbances (negative, positive) and autonomic symptoms.

Twenty patients had neuropathy attributed to paclitaxel and five from cisplatin. Six of the 25 were receiving a taxane at enrollment; the remaining 18 patients has persistent neuropathy at enrollment. Sensory neuropathy improved in 15 patients and motor neuropathy improved in 11. In addition, sensory and motor action potentials (SNAP and CMAP) improved significantly in 21 patients and CMAP improved in 12 patients (non-significant). Twenty-three patients had amelioration of the TNS score, and one patient (receiving concomitant vinorelbine) worsened. Patients showed improved bulbar and limb muscle weakness and sensory disturbance scores after eight weeks of ALC. No change in autonomic symptoms was observed. All patients had normalization of motor strength, deep tendon reflexes, and vibration.

• Limitations include a small sample size of 25 patients with differing levels of neuropathy and no statistical control for confounding variables.
• Although the researchers used comprehensive testing for neuropathy, the use of many variables of neuropathy that were assessed by statistical t tests is cause for concern related to galloping alpha effect, making obtaining statistical significance more likely.
• The one-group, non-randomized design and lack of a control group makes it impossible to infer causality. Testing for these patients (clinical, neurophysiological) is time consuming, painful (nerve conduction), and costly.