No Benefit of Calcium/Magnesium in Preventing Oxaliplatin-Induced Sensory Neurotoxicity in Patients With Colon Cancer
In a phase III N08CB/Alliance trial reported in the Journal of Clinical Oncology, Loprinzi et al assessed whether calcium and magnesium treatment reduced oxaliplatin-related neurotoxicity in patients with colon cancer receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin). They found that calcium/magnesium treatment did not reduce cumulative neurotoxicity and also did not substantially reduce oxaliplatin-related acute neuropathy.
Study Details
In this double-blind trial, 353 patients receiving FOLFOX adjuvant therapy for colon cancer were randomly assigned to receive intravenous calcium gluconate plus magnesium sulfate (1 g of each) immediately before and after chemotherapy (n = 118), calcium/magnesium before and placebo after chemotherapy (n = 116), or placebo before and after (n = 119). The primary endpoint 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 (EORTC QLQ-CIPN20).
Median ages in the 3 groups were 56 to 57 years, and most patients were female (52% in each), white (81%-88%), had stage III disease (74%-76%), and received mFOLFOX6 (92%-94%).
No Reduction in Cumulative Neurotoxicity
The rates of grade 2 or higher neurotoxicity were 43% in the calcium/magnesium before and after group, 46% in the calcium/magnesium before and placebo after group, and 45% in the placebo before and after group. There were no significant differences between the two calcium/magnesium groups and the placebo group in the EORTC QLQ-CIPN sensory neuropathy scale (P = .727 and P = .292) or on the motor neuropathy scale (P = .294 and P =.251) or autonomic neuropathy scale (P = .054 and P = .270). There were no significant differences in time to grade 2 or higher neuropathy on clinician assessment (P = .338 for trend) or using an oxaliplatin-specific neuropathy scale (P = .972 for trend). There was no evidence of benefit of treatment in subgroups defined by age, sex, disease stage, and specific FOLFOX regimens.
For acute neuropathy (within 5 days after each oxaliplatin dose), there was no beneficial effect of treatment in sensitivity to touching cold items, discomfort swallowing cold liquids, or muscle cramps, but a benefit in reducing throat discomfort (P = .036 for trend).
With regard to potential calcium toxicity, there were no differences among treatment groups with regard to diarrhea, constipation, stomach cramping, bowel problems, or laboratory parameters.
The investigators concluded:“This study does not support using calcium/magnesium to protect against oxaliplatin-induced neurotoxicity.”
Charles L. Loprinzi, MD, of the Mayo Clinic, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Public Health Service grants. Study author Axel Grothey, MD, has received research funding from sanofi-aventis.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
