Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy

Dawn L. Hershman*, Joseph M. Unger, Katherine D. Crew, Lori M. Minasian, Danielle Awad, Carol M. Moinpour, Lisa Hansen, Danika L. Lew, Heather Greenlee, Louis Fehrenbacher, James L. Wade, Siu Fun Wong, Gabriel N. Hortobagyi, Frank L. Meyskens, Kathy S. Albain

*Corresponding author for this work

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is common and leads to suboptimal treatment. Acetyl-L-carnitine (ALC) is a natural compound involved in neuronal protection. Studies have suggested ALC may be effective for the prevention and treatment of CIPN. Patients and Methods: A 24-week randomized double-blind trial comparing ALC (3,000 mg per day) with placebo in women undergoing adjuvant taxane-based chemotherapy was conducted. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) -Taxane scale at 12 weeks. Secondary objectives included changes in 24-week end points, functional status (FACT-Trial Outcome Index [TOI]), fatigue (Functional Assessment of Chronic Illness Therapy [FACIT] -Fatigue), and NTX grade. Results: A total of 409 patients were evaluable (208 received ALC; 201, placebo). In a multivariate linear regression, week-12 scores were 0.9 points lower (more CIPN) with ALC than placebo (95% CI, -2.2 to 0.4; P = .17), whereas week-24 scores were 1.8 points lower with ALC (95% CI, -3.2 to -0.4; P = .01). Patients receiving ALC were more likely to have a > 5-point decrease in FACT-NTX scores (38% v 28%; P = .05), and FACT-TOI scores were 3.5 points lower with ALC (P = .03). Grade 3 to 4 neurotoxicity was more frequent in the ALC arm (eight v one). No differences between arms were observed for FACIT-Fatigue or other toxicities. Serum carnitine level increased with ALC but remained stable with placebo. Conclusion: There was no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy.

Original languageEnglish (US)
Pages (from-to)2627-2633
Number of pages7
JournalJournal of Clinical Oncology
Volume31
Issue number20
DOIs
StatePublished - Jul 10 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hershman, D. L., Unger, J. M., Crew, K. D., Minasian, L. M., Awad, D., Moinpour, C. M., Hansen, L., Lew, D. L., Greenlee, H., Fehrenbacher, L., Wade, J. L., Wong, S. F., Hortobagyi, G. N., Meyskens, F. L., & Albain, K. S. (2013). Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. Journal of Clinical Oncology, 31(20), 2627-2633. https://doi.org/10.1200/JCO.2012.44.8738