Two-year trends of taxane-induced neuropathy in women enrolled in a randomized trial of acetyl-l-carnitine (SWOG S0715).

Abstract

10093 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect of taxanes that leads to suboptimal treatment and adversely affects quality of life. Acetyl-L-Carnitine (ALC) was unexpectedly found to increase CIPN in a randomized trial. We investigated the long-term patterns of CIPN among patients enrolled in this trial. Methods: S0715 was a randomized, double-blind, multi-center trial comparing ALC (1000 mg TID) versus placebo for 24 weeks in women with stage I-III breast cancer undergoing taxane-based chemotherapy. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the FACT-Taxane scale at 12 weeks. Additional assessments were conducted at weeks 24, 36, 52 and 104. We examined the reduction of NTX score over 2 years using linear mixed models for longitudinal data, adjusting for stratification factors and the baseline NTX score. Individual assessment time-points were examined using linear regression. Results: SWOG S0715 registered 437 patients, of whom 409 were eligible and evaluable, including 208 assigned to receive ALC and 201 to placebo. Patterns of evaluability were similar over time by arm. The results for the primary outcome of interest, NTX, show a statistically significant (p = 0.01) average difference of -1.39 (95% CI: -2.47 to -0.31) between treatment groups, with the ALC group having lower scores (worse CIPN) on average than the placebo group. These differences were particularly evident at Weeks 24 (p = 0.02), 36 (p = 0.04), and 52 (p = 0.02). A clinically meaningful (≥5 points) reduction in NTX score over baseline was observed more frequently for the ALC vs. control arm (week 24, 41% vs. 34%; week 36, 41% vs. 28%; 1 year, 41% vs. 32%; 2 years, 40% vs. 34%). For both treatment groups 2 year NTX scores were significantly different compared to baseline (p < 0.001). Conclusions: For both groups NTX scores were reduced with taxane-therapy and remained persistently low 2-years following treatment. Twenty-four weeks of ALC therapy resulted in significantly worse CIPN at weeks 24 36 and 52. Understanding the mechanism of this persistent effect may inform prevention and treatment strategies. Clinical trial information: NCT00775645.