Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for the Prevention of Taxane-Induced Neuropathy in Women Undergoing Adjuvant Breast Cancer Therapy

1. Dawn L. Hershman⇑,
2. Joseph M. Unger,
3. Katherine D. Crew,
4. Lori M. Minasian,
5. Danielle Awad,
6. Carol M. Moinpour,
7. Lisa Hansen,
8. Danika L. Lew,
9. Heather Greenlee,
10. Louis Fehrenbacher,
11. James L. Wade III,
12. Siu-Fun Wong,
13. Gabriel N. Hortobagyi,
14. Frank L. Meyskens and
15. Kathy S. Albain

+ Author Affiliations

1. Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger and Danika L. Lew, Southwest Oncology Group Statistical Center; Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Lori M. Minasian, National Cancer Institute, Bethesda, MD; Lisa Hansen, Legacy Good Samaritan Hospital, Portland, OR; Louis Fehrenbacher, Kaiser Permanente Northern California, Vallejo; Siu-Fun Wong, Loma Linda University School of Pharmacy, Loma Linda; Frank L. Meyskens, University of California at Irvine, Orange, CA; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; Gabriel N. Hortobagyi, MD Anderson Cancer Center, Houston, TX; and Kathy S. Albain, Loyola University Chicago Stritch School of Medicine, Maywood, IL.

1. Corresponding author: Dawn L Hershman, MD, MS, Columbia University, 161 Fort Washington Ave, 10-1068, New York, NY 10032; e-mail: dlh23@columbia.edu.

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.