Use of calcium and magnesium infusions in prevention of oxaliplatin induced sensory neuropathy.
OBJECTIVE
Oxaliplatin-related neurotoxicity is frequently dose-limiting. Following retrospective studies suggesting neuroprotective effects of calcium and magnesium (Ca and Mg), we conducted a prospective study using nerve conduction studies (NCS) to evaluate the effectiveness of such infusions in oxaliplatin-related neuropathy.


METHODS
Colorectal cancer patients receiving FOLFOX-4 or capecitabine plus oxaliplatin were randomized to (Arm A) calcium gluconate 1g +15% magnesium sulphate 1g diluted in 100 mL of dextrose 5% or (Arm B) placebo. Neuropathy was assessed using the National Cancer Center common toxicity criteria, oxaliplatin-specific scale and NCS.


RESULTS
This study was terminated prematurely based on the initial negative results of the CONcePT trial. Median follow up was 8.7 months. Overall 22 out of 27 patients experienced neuropathy. The subjective neuropathy rate was 77% in Arm A and 86% in Arm B, (P = 0.6). At the end of treatment, three patients in Arm A and 0 in Arm B had grade 3 numbness (P = 0.09). There was no significant difference in neuropathy between arms, whether during or at the end of treatment. Median objective neuropathy score was 6 in Arm A and 0 in Arm B, (P = 0.02).


CONCLUSIONS
Premature closure of this study limits the interpretation of results. While there was a trend towards reduced subjective acute sensory neuropathy with Ca and Mg, this was not significant. Ca and Mg failed to reduce the rate of cumulative sensory neuropathy and instead increased the rate of abnormal NCS, suggesting a significant difference in perceived sensory and objective neuropathy.
Department of Medical Oncology, National Cancer Centre, Singapore. chay.w.y@nccs.com.sg
Wen-Yee
WY
Chay
Sze-Huey
SH
Tan
Yew-Long
YL
Lo
Simon Yew-Kwang
SY
Ong
Hui-Cheng
HC
Ng
Fei
F
Gao
Wen-Hsin
WH
Koo
Su-Pin
SP
Choo
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002125:Calcium Gluconate / Q000008:administration & dosage*; D000069287:Capecitabine; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000009:adverse effects; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010292:Paresthesia / Q000139:chemically induced / Q000517:prevention & control; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D008278:Magnesium Sulfate; D002955:Leucovorin; D002125:Calcium Gluconate; D005472:Fluorouracil