P16.01 Duloxetine in chemotherapy-induced peripheral neuropathy: experience beyond the clinical trial.

Abstract

Background: Duloxetine, a serotonin‐norepinephrine reuptake inhibitor, is the only agent demonstrated effective in treating pain related with chemotherapy‐induced peripheral neuropathy (CIPN). The phase III randomized, double‐blind, placebo‐controlled trial published in 2013 showed a moderate effect of duloxetine on CIPN pain relief, becoming the drug of first choice. Methods: Consecutive CIPN patients treated with duloxetine were prospectively collected in a single‐institution, between September 2013 and December 2015. Aim of the study was to evaluate the drug's efficacy, rate of compliance and adverse effects profile. Only patients with chronic s CIPN with positive symptoms (pain, numbness and/or paresthesia), and non‐progressive disease were included. CIPN was graded employing the Total Neuropathy Score (TNSc) and National Cancer Institute‐Common Toxicity Criteria v4. Response to duloxetine was assessed with patient global impression of change (PIGC) scale (1: no benefit; 7: excellent response). Results: One hundred patients with symptomatic CIPN were consecutively treated with duloxetine. Median age was 62 (29‐81). 59, 37, 2 and 2 received platinum, taxane, bortezomib and vincristine‐based regimen, respectively, for colorectal (n= 47), breast (n=30), gynecologic (n=6), germinal (n=5), and other (n=12) cancer. Median TNSc was 9 (1‐17). Severity of neuropathy was grade 1 (20%), grade 2 (66%), and grade 3 (14%). Sixteen patients were on treatment with other agents against neuropathic pain. Median PIGC score was 3 [1‐7]. Among responders, 45.5% and 54.5% scored low (2‐4) and high (5‐7) benefit, respectively. Fifty‐seven (57%) patients discontinued early duloxetine due to intolerable side effects (n=37) or lack of efficacy (n=20). No differences on rates of stopping treatment due to side‐effects were observed in men (41%) and women (59%). Most frequently reported adverse events were cognitive (26%), gastrointestinal (14%) and genitourinary (9%). Discontinuation due to perception of lack of efficacy was more frequently reported by men (75% vs 25% p=0.001). Women presented higher punctuations on PIGC scale compared with men (3.8 ± 2.1 vs 1.9 ± 1.7, p=0.005). PIGC scores were significantly higher in patients receiving taxane (3.8 ± 2.4) than platinum (2.5 ± 1.9) agents (p=0.027). No significant differences according severity of neuropathy neither type of chemotherapy were observed in drop‐out and retention rates. Conclusion: More than one‐third of all patients early stop duloxetine due to intolerable side‐effects, which is a rate three times higher than reported. Among treated, women population seems to experiment more benefit. The improvement experienced by patients responding to duloxetine was modest in half of them. Low tolerability and male gender limit duloxetine usefulness in treatment of symptomatic CIPN.