title: Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7.
abstract: OBJECTIVE
  Cumulative sensory neurotoxicity (sNT) is the dose-limiting toxicity of oxaliplatin, which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant settings. In a nonrandomized, retrospective study, intravenous (IV) calcium/magnesium (Ca/Mg) was associated with reduced oxaliplatin-induced sNT.
  
  
  METHODS
  Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) were randomly assigned to Ca/Mg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo, in a double-blinded manner. The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria. An oxaliplatin-specific sNT scale and patient questionnaires were also used to assess sNT. After 104 of 300 planned patients were enrolled, the study was closed. This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy; these data were subsequently found to be incorrect.
  
  
  RESULTS
  Overall, 102 patients were available for analysis. Ca/Mg decreased the incidence of chronic, cumulative, grade 2 or greater sNT, as measured by NCI CTCAE (P = .038) and also by the oxaliplatin-specific sNT scale (P = .018). In addition, acute muscle spasms associated with oxaliplatin were significantly reduced (P = .01) No effect on acute, cold-induced sNT was found. No substantial differences in adverse effects were noted between Ca/Mg and placebo.
  
  
  CONCLUSIONS
  Despite early termination and decreased statistical power, this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer.
authors.affiliation: Mayo Clinic Rochester, Rochester, MN 55905, USA.
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nikcevich
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
authors.forename: John W
authors.initials: JW
authors.lastname: Kugler
authors.forename: Peter T
authors.initials: PT
authors.lastname: Silberstein
authors.forename: Todor
authors.initials: T
authors.lastname: Dentchev
authors.forename: Donald B
authors.initials: DB
authors.lastname: Wender
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Novotny
authors.forename: Umesh
authors.initials: U
authors.lastname: Chitaley
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002125:Calcium Gluconate / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004311:Double-Blind Method; D004338:Drug Combinations; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D011446:Prospective Studies; D012678:Sensation Disorders / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D008278:Magnesium Sulfate; D002125:Calcium Gluconate