title: Electrolyte disorders assessment in solid tumor patients treated with anti-EGFR monoclonal antibodies: a pooled analysis of 25 randomized clinical trials.
abstract: The role of anti-epithelial growth factor receptor monoclonal antibodies (anti-EGFR MoAbs) in treatment-related electrolyte disorders is still controversial. Therefore, we conducted a meta-analysis of published randomized controlled trials (RCTs) to evaluate the incidences and overall risks of all-grade and grade 3/4 electrolyte disorder events. We searched relevant clinical trials from PubMed, EMBASE, and Web of Knowledge databases, meeting proceedings of American Society of Clinical Oncology and the European Society of Medical Oncology, as well as ClinicalTrials.gov. Eligible studies included phases II, III, and IV RCTs. Statistical analysis was performed to calculate the summary incidence, relative risk (RR), and 95 % confidence intervals (CIs) using fixed effects or random effects models based on the heterogeneity of included studies. A total of 16,411 patients from 25 RCTs were included in this meta-analysis. The all-grade incidence of hypomagnesemia related to anti-EGFR MoAbs was 34.0 % (95 % CI 28.0-40.5 %), and that for hypokalemia and hypocalcemia were 14.5 % (95 % CI 8.2-24.4 %) and 16.8 % (95 % CI 14.2-19.7 %), respectively. Compared with chemotherapy alone in colorectal cancer, addition of cetuximab increased the risk of grade 3/4 hypomagnesemia and grade 3/4 hypokalemia with RRs of 7.14 (95 % CI 3.13-16.27, p < 0.001) and 2.19 (95 % CI 1.14-4.23, p = 0.019). Additionally, colorectal cancer patients in panitumumab cases were more vulnerable to grade 3/4 hypomagnesemia and hypokalemia (RR 18.29, 95 % CI 7.29-48.41, p < 0.001, and RR 3.3, 95 % CI 1.32-8.25, p =  .011). Treatment with anti-EGFR MoAbs is associated with significantly higher risks of electrolyte disorders such as hypomagnesemia, hypomagnesemia, and hypocalcemia, especially in colorectal cancer. Rigorous monitoring and early treatment of electrolyte disorders are proposed.
authors.affiliation: Department of Radiation Oncology and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No. 169 Donghu Road, Wuhan, Hubei, 430071, People's Republic of China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuexiao
authors.initials: Y
authors.lastname: Qi
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Caifeng
authors.initials: C
authors.lastname: Gong
authors.forename: Anqi
authors.initials: A
authors.lastname: Yao
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Zhou
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D004573:Electrolytes / Q000378:metabolism*; D066246:ErbB Receptors / Q000276:immunology*; D006801:Humans; D006996:Hypocalcemia / Q000453:epidemiology / Q000209:etiology; D007008:Hypokalemia / Q000453:epidemiology / Q000209:etiology; D007010:Hyponatremia / Q000453:epidemiology / Q000209:etiology; D008274:Magnesium / Q000097:blood; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic
chemical_list: D000911:Antibodies, Monoclonal; D004573:Electrolytes; D066246:ErbB Receptors; D008274:Magnesium