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.
OBJECTIVE
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.


METHODS
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.


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/m(2) 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/m(2) oxaliplatin dosage.
Gamelin
Laurence
L
Department of Medical Oncology and Oncopharmacology, INSERM U564, Anticancer Centre Paul Papin, Angers Cedex, France.
Boisdron-Celle
Michele
M
Delva
Remy
R
Guérin-Meyer
Véronique
V
Ifrah
Norbert
N
Morel
Alain
A
Gamelin
Erick
E
D000368:Aged; D000970:Antineoplastic Agents / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002118:Calcium / Q000627:therapeutic use*; D002125:Calcium Gluconate / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007826:Laryngismus / Q000517:prevention & control; D002955:Leucovorin / Q000627:therapeutic use*; D008274:Magnesium / Q000627:therapeutic use*; D008278:Magnesium Sulfate / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D010292:Paresthesia / Q000517:prevention & control; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D002614:Chelating Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D008278:Magnesium Sulfate; D008274:Magnesium; D002955:Leucovorin; D002125:Calcium Gluconate; D002118:Calcium; D005472:Fluorouracil