title: Addition of gabapentin to a modified FOLFOX regimen does not reduce oxaliplatin-induced neurotoxicity.
abstract: BACKGROUND
  Sensory neurotoxicity is dose limiting for oxaliplatin, an effective drug in the treatment of colorectal cancer (CRC) and other malignancies. This study assessed the impact of gabapentin on oxaliplatin dose intensity and neurotoxicity.
  
  
  METHODS
  Patients with previously untreated metastatic CRC were recruited sequentially to 2 cohorts: the first used a modified FOLFOX6 (fluorouracil/leucovorin/oxaliplatin) regimen alone with oxaliplatin 100 mg/m(2) every 2 weeks (mFOLFOX; n = 40), and the second included the addition of gabapentin (mFOLFOX+G; n = 41). Gabapentin commenced at 300 mg daily, increasing to a maximum of 600 mg 3 times daily to decrease neurotoxicity.
  
  
  RESULTS
  Doses of gabapentin were increased in 31 of 41 patients, with 39% of patients receiving >or= 900 mg daily. The median relative dose intensity of oxaliplatin and requirement for dose reductions or delays because of neurotoxicity were similar in the 2 cohorts. There was no grade 4 neurotoxicity. Whereas grade 3 neurotoxicity was observed in 10% of patients treated with gabapentin versus 21% of patients treated with mFOLFOX alone, there was no statistically significant difference in the severity of neurotoxicity between the 2 cohorts (P = 0.89) or the time to recover from grade 2/3 neurotoxicity (P = 0.97). There were also no significant differences in nonneurologic toxicity or antitumor efficacy between the 2 cohorts.
  
  
  CONCLUSIONS
  This study does not support a role for gabapentin in reducing the incidence or severity of oxaliplatin-induced sensory neurotoxicity.
authors.affiliation: Austin Hospital, Heidelberg, Melbourne, Australia ; e-mail: paul.mitchell@austin.org.au.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Mitchell
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Michael
authors.initials: M
authors.lastname: Michael
authors.forename: Philip
authors.initials: P
authors.lastname: Beale
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.forename: John
authors.initials: J
authors.lastname: Zalcberg
authors.forename: Shane
authors.initials: S
authors.lastname: White
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Thomson
authors.forename: Stephen
authors.initials: S
authors.lastname: Clarke
mesh_terms: D000588:Amines / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D000077206:Gabapentin; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D002955:Leucovorin; D005472:Fluorouracil