Calcium and Magnesium Fail to Prevent Oxaliplatin Neuropathy
David H. Ilson, MD, PhD
Prophylactic administration did not benefit patients receiving adjuvant chemotherapy for colon cancer.
Oxaliplatin is increasingly the standard agent to combine with 5-fluorouracil to treat a broad range of gastrointestinal cancers, including colorectal, pancreaticobiliary, and esophagogastric cancers. However, both acute and chronic sensory neurotoxicity are problematic with this agent, and chronic neurotoxicity is dose limiting in oxaliplatin therapy.
To determine whether prophylactic administration of calcium and magnesium reduces oxaliplatin neurotoxicity, investigators conducted a phase III, multicenter, randomized, double-blind, placebo-controlled trial involving 353 patients with colon cancer receiving FOLFOX (fluorouracil, leucovorin, and oxaliplatin) as adjuvant therapy or as treatment for metastatic disease. Patients were randomized to chemotherapy plus placebo, chemotherapy plus 1gram of calcium gluconate and magnesium sulfate before and after oxaliplatin infusion, or chemotherapy plus 1 gram of calcium and magnesium before and placebo after oxaliplatin infusion. The majority of patients received mFOLFOX6 (93%–94%) and had stage III disease (75%–76%). The primary endpoint was the development of sensory neuropathy as measured by the area under the curve of a sensory neuropathy scale developed by the European Organization for Research and Treatment of Cancer.
Administration of calcium and magnesium — either before oxaliplatin or before and after oxaliplatin — had no effect on the development of sensory neuropathy compared with placebo (P=0.727 and P=0.292, respectively) or incidence of grade 2 or higher neurotoxicity (43%–46%). Calcium and magnesium infusion also had no effect on acute neurotoxicity measures or on the ability to deliver oxaliplatin during the course of therapy.
Citation(s):
Loprinzi CL et al. Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol 2013 Dec 2; [e-pub ahead of print].
