Effects of Calcium and Magnesium on Acute and Chronic Neurotoxicity Caused by Oxaliplatin: A Meta-analysis

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2012 Dec 11

PMID 23226752

Citations 6

Authors

Rui Ao

Yu-Hui Wang

Rui-wen Li

Zheng-Rong Wang

Affiliations

Soon will be listed here.

Abstract

The primary toxicity of oxaliplatin is neurotoxicity. Calcium and magnesium (Ca/Mg) are reported to be beneficial in protecting against this adverse effect. However, the results obtained from clinical trials are not definitive. The aim of this study was to evaluate whether Ca/Mg alleviates the neurotoxicity of oxaliplatin by performing a meta-analysis of the literature involving available randomized controlled trials. Systematic searches for trials were undertaken from the Cochrane Library, MEDLINE, CENTRAL, Embase, CBMdisc and CNKI databases without language limitations. The primary outcome was severe chronic neurotoxicity and the secondary outcome was acute neurotoxicity. Four randomized double-blind trials met the search criteria. The odds ratio (OR) comparing Ca/Mg treatment with placebo was 0.44 (0.23-0.85, P=0.01) for severe chronic neurotoxicity of oxaliplatin (grade ≥2) and 0.41 (0.11-1.49, P=0.18) for acute neurotoxicity. In conclusion, Ca/Mg treatment does not reduce the incidence of acute neurotoxicity of oxaliplatin, but does reduce the incidence of severe chronic neurotoxicity (grade ≥2). No differences were observed in the outcomes of chemotherapy. Thus, Ca/Mg treatment is recommended for use as an adjunct with oxaliplatin.

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References

Knijn N, Tol J, Koopman M, Werter M, Imholz A, Valster F . 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. Eur J Cancer. 2010; 47(3):369-74. DOI: 10.1016/j.ejca.2010.10.006. View

de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J . Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000; 18(16):2938-47. DOI: 10.1200/JCO.2000.18.16.2938. View

Muto O, Ando H, Ono T, Itagaki H, Kobayashi Y, Onuki M . [Reduction of oxaliplatin-related neurotoxicity by calcium and magnesium infusions]. Gan To Kagaku Ryoho. 2007; 34(4):579-81. View

Jadad A, Moore R, Carroll D, Jenkinson C, Reynolds D, Gavaghan D . Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996; 17(1):1-12. DOI: 10.1016/0197-2456(95)00134-4. View

Chay W, Tan S, Lo Y, Ong S, Ng H, Gao F . Use of calcium and magnesium infusions in prevention of oxaliplatin induced sensory neuropathy. Asia Pac J Clin Oncol. 2010; 6(4):270-7. DOI: 10.1111/j.1743-7563.2010.01344.x. View

Kurniali P, Luo L, Weitberg A . Role of calcium/ magnesium infusion in oxaliplatin-based chemotherapy for colorectal cancer patients. Oncology (Williston Park). 2010; 24(3):289-92. View

Gamelin L, Boisdron-Celle M, Delva R, Guerin-Meyer V, Ifrah N, Morel A . 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. Clin Cancer Res. 2004; 10(12 Pt 1):4055-61. DOI: 10.1158/1078-0432.CCR-03-0666. View

Gamelin L, Boisdron-Celle M, Morel A, Poirier A, Berger V, Gamelin E . Oxaliplatin-related neurotoxicity: interest of calcium-magnesium infusion and no impact on its efficacy. J Clin Oncol. 2008; 26(7):1188-9. DOI: 10.1200/JCO.2007.15.3767. View

Cersosimo R . Oxaliplatin-associated neuropathy: a review. Ann Pharmacother. 2004; 39(1):128-35. DOI: 10.1345/aph.1E319. View

10.

Khattak M . Calcium and magnesium prophylaxis for oxaliplatin-related neurotoxicity: is it a trade-off between drug efficacy and toxicity?. Oncologist. 2011; 16(12):1780-3. PMC: 3248777. DOI: 10.1634/theoncologist.2011-0157. View

11.

Therasse P, Arbuck S, Eisenhauer E, Wanders J, Kaplan R, Rubinstein L . New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3):205-16. DOI: 10.1093/jnci/92.3.205. View

12.

Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C . Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000; 18(1):136-47. DOI: 10.1200/JCO.2000.18.1.136. View

13.

Ishibashi K, Okada N, Miyazaki T, Sano M, Ishida H . Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: a prospective randomized study. Int J Clin Oncol. 2010; 15(1):82-7. DOI: 10.1007/s10147-009-0015-3. View

14.

Hochster H, Grothey A, Childs B . Use of calcium and magnesium salts to reduce oxaliplatin-related neurotoxicity. J Clin Oncol. 2007; 25(25):4028-9. DOI: 10.1200/JCO.2007.13.5251. View

15.

Grolleau F, Gamelin L, Boisdron-Celle M, Lapied B, Pelhate M, Gamelin E . A possible explanation for a neurotoxic effect of the anticancer agent oxaliplatin on neuronal voltage-gated sodium channels. J Neurophysiol. 2001; 85(5):2293-7. DOI: 10.1152/jn.2001.85.5.2293. View

16.

Penz M, Kornek G, Raderer M, Ulrich-Pur H, Fiebiger W, Scheithauer W . Subcutaneous administration of amifostine: a promising therapeutic option in patients with oxaliplatin-related peripheral sensitive neuropathy. Ann Oncol. 2001; 12(3):421-2. DOI: 10.1023/a:1011184609963. View

17.

Cascinu S, Catalano V, Cordella L, Labianca R, Giordani P, Baldelli A . Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2002; 20(16):3478-83. DOI: 10.1200/JCO.2002.07.061. View

18.

Meyerhardt J, Mayer R . Systemic therapy for colorectal cancer. N Engl J Med. 2005; 352(5):476-87. DOI: 10.1056/NEJMra040958. View

19.

Grothey A, Nikcevich D, Sloan J, Kugler J, Silberstein P, Dentchev T . Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7. J Clin Oncol. 2010; 29(4):421-7. PMC: 3058288. DOI: 10.1200/JCO.2010.31.5911. View

20.

Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T . Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004; 350(23):2343-51. DOI: 10.1056/NEJMoa032709. View