A phase III, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of pregabalin in the prevention and reduction of oxaliplatin-induced painful neuropathy (PreOx).

3575 Background: Patients with colorrectal cancer receiving Oxaliplatin usually develop acute and chronic painful chemotherapy-induced peripheral neuropathy (CIPN). Despite having different mechanisms, both conditions lead to central sensitization (CS). Recent data suggest that the degree of CS after acute use of Oxaliplatin increases the risk of painful CIPN. We hypothesized that preemptive use of anti-hyperalgesic drug (pregabaline) during Oxaliplatin infusions would decrease the incidence of chronic painful CIPN. Methods: Pain-free, chemotherapy-naïve patients (stage III/IV) receiving at least one complete cycle of modified FLOX (5-FU+leucovorin for 6 consecutive weeks+oxaliplatin 85 mg/m2 at weeks 1, 3 and 5, every 8 weeks) were randomised (1:1). Eligible patients received either pregabaline or placebo (150-600mg/d) for three days before and three days after each oxaliplatin infusion. Patients were followed for 3-6 months after the end of chemotherapy. Clinical assessments were performed at baseline, at the end of chemotherapy treatment and after the followup period. The main outcome was average pain at the last visit assessed by the visual numerical scale (0-10) item of the Brief Pain Inventory in pts with neuropathic pain according to the Douleur Neuropathique-4 score (DN4). Secondary endpoints were pain interference (BPI), pain dimensions (McGill Pain Questionnaire), score of the Neuropathic Pain Symptom Inventory (NPSI). Results: 206 patients (56.6±11yo, 111 female) were enrolled. Both groups presented similar baseline demographic characteristics (p > 0.20). The cumulative dose of oxaliplatin was similar between groups throughout the study. Data from 82 patients in the pregabaline and 84 in the placebo group were retained for analises. At the last visit, pain intensity in the pregabaline group was 0.85±2.35 and 0.88±2.40 in the placebo group (p = 0.673). Scores from other pain scales did not differ between groups. Conclusions: The preemptive use of the antihyperalgesic drug pregabaline during oxaliplatin infusions was safe, but did not decrease the incidence of chronic pain related to CIPN. Clinical trial information: NCT0145016.