title: Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Columbia University, 161 Fort Washington Ave, 10-1068, New York, NY 10032, USA. dlh23@columbia.edu
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Hershman
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Unger
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Crew
authors.forename: Lori M
authors.initials: LM
authors.lastname: Minasian
authors.forename: Danielle
authors.initials: D
authors.lastname: Awad
authors.forename: Carol M
authors.initials: CM
authors.lastname: Moinpour
authors.forename: Lisa
authors.initials: L
authors.lastname: Hansen
authors.forename: Danika L
authors.initials: DL
authors.lastname: Lew
authors.forename: Heather
authors.initials: H
authors.lastname: Greenlee
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: James L
authors.initials: JL
authors.lastname: Wade
authors.forename: Siu-Fun
authors.initials: SF
authors.lastname: Wong
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Frank L
authors.initials: FL
authors.lastname: Meyskens
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Albain
mesh_terms: D000108:Acetylcarnitine / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D009416:Nerve Regeneration / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D043823:Taxoids / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000108:Acetylcarnitine