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Clinical Cancer Research Vol. 10, 4055-4061, June 15, 2004
© 2004 American Association for Cancer Research

Clinical Trials

Prevention of Oxaliplatin-Related Neurotoxicity by Calcium and Magnesium Infusions

A Retrospective Study of 161 Patients Receiving Oxaliplatin Combined with 5-Fluorouracil and Leucovorin for Advanced Colorectal Cancer

Laurence Gamelin4, Michele Boisdron-Celle1,2, Remy Delva1, Véronique Guérin-Meyer1, Norbert Ifrah3, Alain Morel1,2 and Erick Gamelin1,2

1 Department of Medical Oncology and Oncopharmacology, 2 INSERM U564, Anticancer Centre Paul Papin, and 3 Department of Hematology, and 4 Antipoison Center, University Hospital, Angers Cedex, France

Purpose: Oxaliplatin is active in colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. It may come from an effect on neuronal voltage-gated Na channels, via the liberation one its metabolite, oxalate. We decided to use Ca and Mg as oxalate chelators.

Experimental Design: A retrospective cohort of 161 patients treated with oxaliplatin + 5-fluorouracil and leucovorin for advanced colorectal cancer, with three regimens of oxaliplatin (85 mg/m2/2w, 100/2w, 130/3w) was identified. Ninety-six patients received infusions of Ca gluconate and Mg sulfate (1 g) before and after oxaliplatin (Ca/Mg group) and 65 did not.

Results: Only 4% of patients withdrew for neurotoxicity in the Ca/Mg group versus 31% in the control group (P = 0.000003). The tumor response rate was similar in both groups. The percentage of patients with grade 3 distal paresthesia was lower in Ca/Mg group (7 versus 26%, P = 0.001). Acute symptoms such as distal and lingual paresthesia were much less frequent and severe (P = 10-7), and pseudolaryngospasm was never reported in Ca/Mg group. At the end of the treatment, 20% of patients in Ca/Mg group had neuropathy versus 45% (P = 0.003). Patients with grade 2 and 3 at the end of the treatment in the 85 mg/m2 oxaliplatin group recovered significantly more rapidly from neuropathy than patients without Ca/Mg.

Conclusions: Ca/Mg infusions seem to reduce incidence and intensity of acute oxaliplatin-induced symptoms and might delay cumulative neuropathy, especially in 85 mg/m2 oxaliplatin dosage.




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