Acetyl-L-carnitine Ineffective for Taxane-related Peripheral Neuropathy
Various studies have suggested that acetyl-L-carnitine, a natural compound involved in neuronal protection, may be effective in preventing and treating sensory neuropathy. Dawn L. Hershman, MD, MS, of Columbia University Medical Center, and colleagues recently assessed whether daily acetyl-L-carnitine could reduce chemotherapy-induced peripheral neuropathy in women receiving adjuvant taxane therapy for breast cancer. The study, published online in the Journal of Clinical Oncology, showed that acetyl-L-carnitine was associated with no improvement in chemotherapy-induced peripheral neuropathy at 12 weeks and with worse peripheral neuropathy at 24 weeks.
Study Details
In this 24-week double-blind trial, 409 patients with stage I to III breast cancer undergoing taxane-based adjuvant therapy were randomly assigned to receive acetyl-L-carnitine 3,000 mg/d (n = 208) or placebo (n = 201). The primary objective was to determine if acetyl-L-carnitine prevents chemotherapy-induced peripheral neuropathy as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT)-Taxane scale at 12 weeks.
Patients in the acetyl-L-carnitine and placebo groups were well matched for age (median 52 and 50 years), race/ethnicity, type of taxane treatment, performance status (0 in 75% and 73% of patients, respectively), disease stage (II in 53% and 54% of patients, respectively; III in 20% and 21%), and baseline serum carnitine level.
Effect at Week 12
Week 12 FACT-NTX assessment (in 92% of patients in the acetyl-L-carnitine group and 90% of patients in the placebo group) showed that the mean scores were reduced from baseline (worse chemotherapy-induced peripheral neuropathy) by 5.2 points in the acetyl-L-carnitine group and 4.9 points in the placebo group. On linear regression analysis adjusting for baseline score, type of taxane treatment, and age, the 12-week score was a nonsignificant 0.9 points lower in the acetyl-L-carnitine group versus the placebo group (P = .17). Reductions of greater than 5 points occurred in 38% of patients receiving acetyl-L-carnitine and 30% of patients receiving placebo (odds ratio [OR] = 1.48, P = .08).
Effect at Week 24
At the week 24 assessment (in 84% of patients receiving acetyl-L-carnitine and 86% of patients receiving placebo), FACT-NTX scores were reduced from baseline by 5.3 points in the acetyl-L-carnitine group and 3.6 points in the placebo group. Linear regression analysis showed that acetyl-L-carnitine treatment was associated with a significant 1.8 point reduction compared with placebo (P = .01). Reductions of greater than 5 points occurred in 38% of patients receiving acetyl-L-carnitine and 28% of patients receiving placebo patients (OR = 1.57, P = .05). Grade 3 or 4 neuropathy occurred in eight patients receiving acetyl-L-carnitine and one patient on placebo (P = .46). There were no differences between groups with regard to treatment delays or chemotherapy dose reductions.
Functional Status and Fatigue
Functional status assessed by the FACT-Trial Outcome Index scale did not differ between the two groups at week 12, but the acetyl-L-carnitine group had a significantly lower score (poorer functional status) at week 24 (3.5-point reduction vs placebo, P = .03). There were no differences between groups at 12 or 24 weeks in fatigue assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale. Throughout the trial, serum carnitine levels were elevated in the acetyl-L-carnitine group and remained stable in the placebo group.
The investigators concluded, “There was no evidence that acetyl-L-carnitine affected chemotherapy-induced peripheral neuropathy at 12 weeks; however, acetyl-L-carnitine significantly increased chemotherapy-induced peripheral neuropathy by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased chemotherapy-induced peripheral neuropathy. Patients should be discouraged from using supplements without proven efficacy.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
