Efficacy of venlafaxine for the prevention and relief of acute neurotoxicity of oxaliplatin: Results of EFFOX, a randomized, double-blinded, placebo-controlled prospective study

Abstract

9533 Background: Neurosensory toxicity of oxaliplatin is dose-limiting and presents as two distinct clinical syndromes: acute symptoms and cumulative peripheral neuropathy. Methods: From October 2005 to May 2008, patients (pts) presenting oxaliplatin-induced acute neurotoxicity were randomized in a double-blinded study, to receive either arm A: venlafaxine hydrochloride (Effexor, Wyeth Pharmaceuticals Inc.) 50 mg 1 hour prior oxaliplatin infusion and venlafaxine extended release 37.5 mg b.i.d. from day 2 to day 11, either arm B : placebo. The primary endpoint was percentage of pts without acute neuropathy. The study was designed to detect, with 54 pts, a difference of 25%. The neurotoxicity was evaluated using a numeric rating scale of symptoms relief and the Neuropathic Pain Symptom Inventory (Pain 2004;108(3):248–57). Results: 45 pts were included (male : 24; median age : 67.5). Most pts had colo-rectal cancer (75.6%). The two most used chemotherapy regimens were FOLFOX (82.2%) and GEMOX (11.1%). Median number of cycles administered at inclusion was 5. In January 2009, 16 pts out of 22 in arm A (venlafaxine) and 21 pts out of 23 in arm B (placebo) were evaluable. Venlafaxine reduced the incidence of neurosensory acute symptoms : 35.3 % in arm A vs 76.2% in arm B (p=.023, Fisher's exact test). Side effects were emesis (4 pts) and somnolence (3 pts). Conclusions: Venlafaxine is effective for prevention and relief of oxaliplatin-induced acute neurotoxicity. No significant financial relationships to disclose.