title: MC11C4: a pilot randomized, placebo-controlled, double-blind study of venlafaxine to prevent oxaliplatin-induced neuropathy.
abstract: OBJECTIVE
  Previous pilot data suggested that venlafaxine could prevent acute and chronic oxaliplatin-related neuropathy. The purpose of this randomized, placebo-controlled, double-blinded pilot study was to obtain additional data to support conducting a phase III trial to test the use of venlafaxine to prevent oxaliplatin neurotoxicity.
  
  
  METHODS
  Fifty patients, scheduled to undergo oxaliplatin-based therapy (FOLFOX) for stages II-III (67%) or stage IV (33%) colon cancer, were randomized to receive venlafaxine extended release (37.5 mg) or placebo, twice daily, through their last dose of oxaliplatin and then titrated off. Neurotoxicity was evaluated via several patient- and physician-reported measures, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20) instrument.
  
  
  RESULTS
  Baseline patient characteristics were equivalent for the two arms, with a median age of 60 years. There was a trend toward benefit for the venlafaxine arm, when evaluated by the oxaliplatin-specific neuropathy scale and by acute neuropathy measures of throat discomfort and discomfort swallowing cold liquids, the latter only for the first two oxaliplatin doses. These trends were outweighed by a lack of any such trends in all other measurements including the following: (1) the CIPN20 sensory subscale (P = 0.55, primary endpoint), physician-completed NCI CTCAE assessment, or cumulative administered oxaliplatin doses (median 716 vs 631 mg for placebo and venlafaxine, respectively, P = 0.34).
  
  
  CONCLUSIONS
  The present study neither supports the use of venlafaxine for preventing oxaliplatin-induced neuropathy in clinical practice nor the initiation of a phase III trial to investigate venlafaxine in this setting.
authors.affiliation: Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Collin
authors.initials: C
authors.lastname: Zimmerman
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Atherton
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Pachman
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Drew
authors.initials: D
authors.lastname: Seisler
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Wagner-Johnston
authors.affiliation: Cancer Center of Kansas, Wichita, KS, USA.
authors.forename: Shaker
authors.initials: S
authors.lastname: Dakhil
authors.affiliation: Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Lafky
authors.affiliation: Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.|Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.affiliation: Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.affiliation: Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA. cloprinzi@mayo.edu.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
mesh_terms: D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D010865:Pilot Projects; D011788:Quality of Life; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D009944:Organoplatinum Compounds; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D000077150:Oxaliplatin; D000069470:Venlafaxine Hydrochloride
keywords: Chemotherapy-induced neuropathy prevention; Venlafaxine