A Drug-Interaction Study of Effects of Calcium and Magnesium Infusions on Oxaliplatin Pharmacokinetics, Motor Nerve Hyperexcitability and Acute Neurotoxicity Symptoms in Colorectal Cancer Patients — ASN Events
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A Drug-Interaction Study of Effects of Calcium and Magnesium Infusions on Oxaliplatin Pharmacokinetics, Motor Nerve Hyperexcitability and Acute Neurotoxicity Symptoms in Colorectal Cancer Patients (#173)

Catherine H Han 1 2 , Prashannata Khwaounjoo 2 , Dean H Kilfoyle 3 , Andrew G Hill 1 2 , Mark J McKeage 1 2
  1. Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand
  2. Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand
  3. Department of Neurophysiology, Auckland City Hospital, Auckland, New Zealand

Aims: Calcium and magnesium (Ca/Mg) infusions have been suggested as an effective intervention for preventing oxaliplatin-induced neurotoxicity, but their effects on oxaliplatin pharmacokinetics, motor nerve hyperexcitability and acute neurotoxicity symptoms are unclear.

Methods: Colorectal cancer patients undergoing oxaliplatin-based chemotherapy were randomised to receive Ca/Mg (1g Ca Gluconate plus 1g MgSO4) on cycle 1 and placebo (vehicle alone) on cycle 2, or to receive the same treatments in the opposite sequence. Primary endpoint was plasma pharmacokinetics of intact oxaliplatin and free platinum. Secondary endpoints included electromyography (EMG) detection of abnormal spontaneous high-frequency motor unit action potential discharges; and patient-reported acute neurotoxicity symptoms and their preferred study treatment for reducing these symptoms. 

Results:The planned accrual target was achieved. Nineteen of 20 enrolled patients completed the study. Plasma pharmacokinetics of intact oxaliplatin and free platinum were similar when oxaliplatin was given with Ca/Mg or placebo (ratio of geometric means of AUC0-t with Ca/Mg or placebo: intact oxaliplatin, 0.95 (90% CI, 0.90 – 1.01); free platinum, 0.99 (90% CI, 0.94 – 1.05)). EMG motor nerve hyperexcitability scores were similar with Ca/Mg and placebo (mean difference in EMG score between Ca/Mg and placebo: -0.3 (95% CI, -2.2 – 1.6)). Patient-reported acute neurotoxicity symptoms were similar in frequency with Ca/Mg and placebo.  For reducing neurotoxic symptoms, fewer patients preferred Ca/Mg than placebo or neither treatment (26% versus 74%; P<0.01).

Conclusions: Ca/Mg infusions do not alter the clinical pharmacokinetics of oxaliplatin and do not seem to reduce its motor nerve hyperexcitability or acute neurotoxicity symptoms.