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

A B S T R A C T PurposeChemotherapy-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 MethodsA 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 ( ResultsA 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, Ϫ2.2 to 0.4; P ϭ .17), whereas week-24 scores were 1.8 points lower with ALC (95% CI, Ϫ3.2 to Ϫ0.4; P ϭ .01). Patients receiving ALC were more likely to have a Ͼ 5-point decrease in FACT-NTX scores (38% v 28%; P ϭ .05), and FACT-TOI scores were 3.5 points lower with ALC (P ϭ .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. ConclusionThere 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.

Chemotherapy-induced peripheral neuropathy: review for clinical practice

“…The Southwest Oncology Group (SWOG) S0715 study has contradicted initial optimism after evaluating the role of Alcar in preventing CIPN in 409 patients receiving taxanes during adjuvant breast cancer therapy. With regard to control group, there has been a trend to worsening neurological symptoms in the intervention group after 24 weeks of follow-up 36 . A randomized placebo-controlled study has evaluated the efficacy of baclofen (10mg), amitriptyline (40mg) and ketamine (20mg) in a lecithin in organogel (BAK-OLP) versus placebo (OLP) to treat CIPN during 4 weeks in 208 patients.…”

Pharmacological Approaches and Natural Products for Prevention of Chemotherapy-Induced Peripheral Neuropathy - A Review

“…More encouraging results were obtained with the administration of all-trans retinoic acid in an animal model and patients with lung cancer [33]. Conversely, acetyl-L-carnitine increased CIPN at 24 weeks compared with placebo although no difference was observed at 12 weeks in women undergoing adjuvant breast cancer therapy [34]. New alternative therapies have been considered for prevention of CIPN and there is considerable interest in the prophylactic role of natural products, such as curcumin [35], matricaria chamomilla [36], ginkgo biloba extract [37], and green tea [38].…”

Nutraceuticals for Fertility and Erectile Health: A Brief Overview of What Works and What Is Worthless

“…Yet a recent concern over L-carnitine utilization by potentially heart disease producing flora received attention [46], but so did a meta-analysis demonstrating a lower risk of cardiovascular events with L-carnitine from secondary prevention studies [47]. Another recent phase 3 trial in cancer to reduce chemotherapy induced neuropathy actually found an increase in neuropathy with this supplement at 3,000 mg per day [48]. Therefore, the controversy of whether or not this supplement could be beneficial will continue.…”