Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance)

J Clin Oncol. 2014 Apr 1;32(10):997-1005. doi: 10.1200/JCO.2013.52.0536. Epub 2013 Dec 2.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: This study does not support using calcium/magnesium to protect against oxaliplatin-induced neurotoxicity.

Trial registration: ClinicalTrials.gov NCT01099449.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intravenous
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Calcium / administration & dosage
  • Calcium / therapeutic use*
  • Cold Temperature
  • Colonic Neoplasms / drug therapy*
  • Double-Blind Method
  • Female
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / adverse effects
  • Magnesium / administration & dosage
  • Magnesium / therapeutic use*
  • Male
  • Middle Aged
  • Muscle Cramp / chemically induced
  • Muscle Cramp / prevention & control
  • Organoplatinum Compounds / adverse effects*
  • Oxaliplatin
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / prevention & control*
  • Sensation Disorders / chemically induced
  • Sensation Disorders / prevention & control

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Magnesium
  • Leucovorin
  • Calcium
  • Fluorouracil

Supplementary concepts

  • Folfox protocol

Associated data

  • ClinicalTrials.gov/NCT01099449