Efficacy of Venlafaxine for the Prevention and Relief of Oxaliplatin-Induced Acute Neurotoxicity: Results of EFFOX, a Randomized, Double-Blind, Placebo-Controlled Phase III Trial

Ann Oncol. 2012 Jan;23(1):200-5. doi: 10.1093/annonc/mdr045. Epub 2011 Mar 22.

Abstract

Background: Oxaliplatin neurosensory toxicity is dose limiting and may present as acute symptoms and/or cumulative peripheral neuropathy.

Patients and methods: From October 2005 to May 2008, patients with oxaliplatin-induced acute neurotoxicity were randomized into a double-blind study, to receive either venlafaxine 50 mg 1 h prior oxaliplatin infusion and venlafaxine extended release 37.5 mg b.i.d. from day 2 to day 11 or placebo. Neurotoxicity was evaluated using numeric rating scale (NRS) for pain intensity and experienced relief under treatment, the Neuropathic Pain Symptom Inventory and the oxaliplatin-specific neurotoxicity scale. The primary end point was the percentage of patients with a 100% relief under treatment.

Results: Forty-eight patients were included (27 males, median age: 67.6 years). Most patients had colorectal cancer (72.9%). Median number of cycles administered at inclusion was 4.5 (mean cumulative oxaliplatin dose: 684.6 mg). Twenty out of 24 patients in arm A (venlafaxine) and 22 out of 24 patients in arm B (placebo) were assessable for neurotoxicity. Based on the NRS, full relief was more frequent in the venlafaxine arm: 31.3% versus 5.3% (P=0.03). Venlafaxine side-effects included grade 1-2 nausea (43.1%) and asthenia (39.2%) without grade 3-4 events.

Conclusion: Venlafaxine has clinical activity against oxaliplatin-induced acute neurosensory toxicity.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Colorectal Neoplasms / drug therapy
  • Cyclohexanols / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurotoxicity Syndromes / prevention & control*
  • Organoplatinum Compounds / adverse effects*
  • Oxaliplatin
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / prevention & control
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Venlafaxine Hydrochloride

Substances

  • Antineoplastic Agents
  • Cyclohexanols
  • Organoplatinum Compounds
  • Serotonin Uptake Inhibitors
  • Oxaliplatin
  • Venlafaxine Hydrochloride