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

• Published in: Clinical cancer research 2004-06, Vol.10 (12), p.4055-4061
• Main Authors: GAMELIN, Laurence, BOISDRON-CELLE, Michele, DELVA, Remy, GUERIN-MEYER, Véronique, IFRAH, Norbert, MOREL, Alain, GAMELIN, Erick
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic agents; Antineoplastic Agents - toxicity; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Calcium - therapeutic use; Calcium Gluconate - therapeutic use; Chelating Agents - therapeutic use; Female; Fluorouracil - therapeutic use; Humans; Laryngismus - prevention & control; Leucovorin - therapeutic use; Magnesium - therapeutic use; Magnesium Sulfate - therapeutic use; Male; Medical sciences; Middle Aged; Organoplatinum Compounds - toxicity; Paresthesia - prevention & control; Pharmacology. Drug treatments; Retrospective Studies; Time Factors; Treatment Outcome; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0666

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. A retrospective cohort of 161 patients treated with oxaliplatin + 5-fluorouracil and leucovorin for advanced colorectal cancer, with three regimens of oxaliplatin (85 mg/m(2)/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. 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/m(2) oxaliplatin group recovered significantly more rapidly from neuropathy than patients without Ca/Mg. Ca/Mg infusions seem to reduce incidence and intensity of acute oxaliplatin-induced symptoms and might delay cumulative neuropathy, especially in 85 mg/m(2) oxaliplatin dosage.