A Double-Blind, Randomized Phase II Study to Evaluate the Safety and Efficacy of Acetyl-L-Carnitine in the Prevention of Sagopilone-Induced Peripheral Neuropathy

Abstract

Background. Peripheral neuropathy (PN) is a recognized side effect of microtubule‐targeting agents and the most clinically relevant toxicity observed with the epothilone sagopilone (SAG). Studies suggest that acetyl‐L‐carnitine (ALC) may prevent chemotherapy‐induced PN. We conducted a prospective, placebo (PBO)‐controlled, double‐blind, randomized trial to investigate the safety and efficacy of ALC for the prevention of SAG‐induced PN. Methods. Patients with ovarian cancer (OC) or castration‐resistant prostate cancer (CRPC) and no evidence of neuropathy received SAG (16 mg/m2 intravenously over 3 hours every 3 weeks) with ALC (1,000 mg every 3 days) or placebo (PBO). The primary endpoint was incidence of PN within six or fewer cycles in both treatment groups. Results. Overall, 150 patients enrolled (98 OC patients, 52 CRPC patients), with 75 per treatment arm. No significant difference in overall PN incidence was observed between treatment arms. The incidence of grade ≥3 PN was significantly lower in the ALC arm in OC patients. Median duration of neuropathy was similar between treatment arms. The best overall response (according to the modified Response Evaluation Criteria in Solid Tumors), response according to tumor markers, time‐to‐event variables, and discontinuations because of adverse events (AEs) were comparable between treatment arms. Conclusion. Administration of ALC with SAG did not result in a significant difference in overall PN incidence compared with a PBO. OC patients in the SAG/ALC arm had a significantly lower incidence of grade 3 or 4 PN compared with OC patients in the SAG/PBO arm.

SANIST: a rapid mass spectrometric SACI/ESI data acquisition and elaboration platform for verifying potential candidate biomarkers

“…A correlation between mitochondrial dysfunction and differentially expressed carnitine has been previously described in rats in the context of ifosfamide chemotherapy toxicity . Propionyl‐L‐carnitine and acetyl‐L‐carnitine have shown to be promising in the management of therapy‐induced peripheral neuropathy in PCa patients without affecting therapeutic efficacy, and androgen deprivation therapy has been shown to significantly decrease numerous carnitines, including octanoylcarnitine and decanoylcarnitine …”

“…Differentially expressed plasma carnitine levels have been found in cancer patients, often ascribed to malnutrition . Clinically, L‐carnitine and its derivatives (acetyl‐L‐carnitine; propionyl‐L‐carnitine) are under study to combat wasting and chemotherapy‐induced peripheral neuropathy . Carnitine supplementation in several experimental models has been shown to slow down tumor growth .…”

Chemotherapy-induced peripheral neuropathy in the adult

“…This is the first trial demonstrating that a nutritional supplement increased CIPN. A phase II European multicenter clinical trial failed to support the efficacy of ALC against the neurotoxicity induced by sagopilone, an analog of ixabepilone [47].…”

Effects of acetyl‐L‐carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double‐blind, controlled trial

“…The therapeutic effect of ALC on DPN was supported by previous studies, in which ALC improved visual analog scale and other symptoms scores, as well as electrophysiological parameters 12,[19][20][21] . Additionally, ALC has also been studied to treat peripheral neuropathy induced by chemotherapy [23][24][25][26][27] or antiviral treatment [28][29][30] . Most of these trials were uncontrolled or placebo-controlled, and showed that ALC is efficacious and safe.…”