title: 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.
abstract: BACKGROUND
  Oxaliplatin neurosensory toxicity is dose limiting and may present as acute symptoms and/or cumulative peripheral neuropathy.
  
  
  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.
  
  
  CONCLUSIONS
  Venlafaxine has clinical activity against oxaliplatin-induced acute neurosensory toxicity.
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Paris. Electronic address: jean-philippe.durand@cch.aphp.fr.
authors.forename: J P
authors.initials: JP
authors.lastname: Durand
authors.affiliation: Department of Medical Oncology, Saint Joseph Hospital, Paris.
authors.forename: G
authors.initials: G
authors.lastname: Deplanque
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Paris.
authors.forename: V
authors.initials: V
authors.lastname: Montheil
authors.affiliation: Department of Gastro-Enterology, Saint Louis Teaching Hospital, AP-HP, Paris.
authors.forename: J M
authors.initials: JM
authors.lastname: Gornet
authors.affiliation: Department of Medical Oncology, Georges Pompidou European Hospital, AP-HP, Paris.
authors.forename: F
authors.initials: F
authors.lastname: Scotte
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Paris.
authors.forename: O
authors.initials: O
authors.lastname: Mir
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Paris.
authors.forename: A
authors.initials: A
authors.lastname: Cessot
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Paris.
authors.forename: R
authors.initials: R
authors.lastname: Coriat
authors.affiliation: Department of Medical Oncology, Beaujon Teaching Hospital, AP-HP, Clichy.
authors.forename: E
authors.initials: E
authors.lastname: Raymond
authors.affiliation: Department of Gastro-Enterology, Ambroise Paré Teaching Hospital, AP-HP, Boulogne-Billancourt.
authors.forename: E
authors.initials: E
authors.lastname: Mitry
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Paris.
authors.forename: P
authors.initials: P
authors.lastname: Herait
authors.affiliation: Oncology Unit, Sanofi Aventis France, Paris, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Yataghene
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Paris.
authors.forename: F
authors.initials: F
authors.lastname: Goldwasser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003511:Cyclohexanols / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride
chemical_list: D000970:Antineoplastic Agents; D003511:Cyclohexanols; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride