title: Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance).
abstract: OBJECTIVE
  Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy. Intravenous calcium and magnesium have been extensively used to reduce oxaliplatin-induced neurotoxicity. This trial was designed to definitively test whether calcium/magnesium decreases oxaliplatin-related neurotoxicity.
  
  
  METHODS
  In all, 353 patients with colon cancer undergoing adjuvant therapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were randomly assigned to intravenous calcium/magnesium before and after oxaliplatin, a placebo before and after, or calcium/magnesium before and placebo after. The primary end point was cumulative neurotoxicity measured by the sensory scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 tool.
  
  
  RESULTS
  There were no statistically significant neuropathy differences among the study arms as measured by the primary end point or additional measures of neuropathy, including clinician-determined measurement of the time to grade 2 neuropathy by using the National Cancer Institute Common Terminology Criteria for Adverse Events scale or an oxaliplatin-specific neuropathy scale. In addition, calcium/magnesium did not substantially decrease oxaliplatin-induced acute neuropathy.
  
  
  CONCLUSIONS
  This study does not support using calcium/magnesium to protect against oxaliplatin-induced neurotoxicity.
authors.affiliation: Charles L. Loprinzi, Rui Qin, Pamela Atherton, Drew Seisler, and Axel Grothey, Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN; Shaker R. Dakhil, Wichita Community Clinical Oncology Program, Wichita, KS; Louis Fehrenbacher, Kaiser Permanente-Vallejo, Vallejo, CA; Kathleen A. Flynn, Michigan Cancer Research Consortium, Ann Arbor, MI; Rubina Qamar, Aurora Cancer Care-Milwaukee West, Wauwatosa, WI; and Grant C. Lewis, Summit Cancer Care, Savannah, GA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Flynn
authors.forename: Pamela
authors.initials: P
authors.lastname: Atherton
authors.forename: Drew
authors.initials: D
authors.lastname: Seisler
authors.forename: Rubina
authors.initials: R
authors.lastname: Qamar
authors.forename: Grant C
authors.initials: GC
authors.lastname: Lewis
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002118:Calcium / Q000008:administration & dosage / Q000627:therapeutic use*; D003080:Cold Temperature; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects; D008274:Magnesium / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009120:Muscle Cramp / Q000139:chemically induced / Q000517:prevention & control; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D012678:Sensation Disorders / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D008274:Magnesium; D002955:Leucovorin; D002118:Calcium; D005472:Fluorouracil