The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatin-based systemic treatment in advanced colorectal cancer patients.
BACKGROUND
Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment. Calcium and magnesium (Ca/Mg) infusions are frequently used to prevent this toxicity. However, concerns about a negative impact of Ca/Mg infusions on outcome have been raised. We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer (ACC) patients treated in the phase III CAIRO2 study.


METHODS
Seven hundred and fifty five previously untreated ACC patients were randomised between treatment with capecitabine, oxaliplatin and bevacizumab or the same combination with the addition of cetuximab. Patients were retrospectively divided into two groups: patients in the Ca/Mg(+) group received Ca/Mg at least during their first treatment cycle, and patients in the Ca/Mg(-) group did not.


RESULTS
Seven hundred and thirty two patients were evaluable for this analysis. The Ca/Mg(+) group consisted of 551 patients, the Ca/Mg(-) group consisted of 181 patients. The incidence of all grade neurotoxicity in the Ca/Mg(+) group and the Ca/Mg(-) group was 85% and 92%, respectively (p = 0.02), and the incidence of grade ≥ 2 neurotoxicity was 40% and 45%, respectively (p = 0.22). The median PFS in the Ca/Mg(+) versus Ca/Mg(-) group was 10.1 versus 10.7 months (p = 0.92), the median OS was 19.8 versus 20.7 months (p = 0.10), and the response rate was 43.1% versus 50% (p = 0.11), respectively.


CONCLUSIONS
In this largest retrospective analysis to date we observed that Ca/Mg infusions significantly reduced all grade oxaliplatin-related neurotoxicity. Ca/Mg infusions did not affect the clinical efficacy of treatment.
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
N
N
Knijn
J
J
Tol
M
M
Koopman
M J B P
MJ
Werter
A L T
AL
Imholz
F A A
FA
Valster
L
L
Mol
A D
AD
Vincent
S
S
Teerenstra
C J A
CJ
Punt
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000068258:Bevacizumab; D002118:Calcium / Q000008:administration & dosage*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008274:Magnesium / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D012189:Retrospective Studies; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D008274:Magnesium; D002118:Calcium; D005472:Fluorouracil