title: Risk of grade 3-4 diarrhea and mucositis in colorectal cancer patients receiving anti-EGFR monoclonal antibodies regimens: A meta-analysis of 18 randomized controlled clinical trials.
abstract: The anti-Epidermal Growth Factor Receptor monoclonal antibodies (anti-EGFR MoAbs) are beneficial in the treatment of wild type (WT) KRAS colorectal cancer, but are burdened by serious toxicities. We conducted a systematic review and meta-analysis to determine incidence and relative risk (RR) of severe and life-threatening diarrhoea and mucositis in colorectal cancer patients and WT-KRAS subpopulation. PubMed and Embase were searched for trials comparing the same therapeutic regimens with or without anti-EGFR for colorectal cancer. Data on severe and life-threatening diarrhoea and mucositis were extracted from 18 studies involving 13,382 patients. Statistical analyses calculated incidence of AEs, RRs and 95% confidence intervals by using either random or fixed effects models. Patients receiving anti-EGFR MoAbs showed an increased risk of diarrhoea (RR: 1.66, CI 1.52-1.80) and mucositis (RR: 3.44, CI 2.66-4.44). The risk was similar among WT-KRAS patients. Prevention and risk reduction strategies of these AEs are mandatory to optimize clinical outcomes.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Miroddi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. Electronic address: csterrantino@unime.it.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Sterrantino
authors.affiliation: Service of Medical Statistics and Information Technology (SeSMIT), Fatebenefratelli Hospital-Isola Tiberina, Rome, Italy; Laboratory of Neurodegeneration, IRCSS San Raffaele Pisana, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Simonelli
authors.affiliation: Health Economics Consulting group, University of East Anglia, Norwich, United Kingdom.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ciminata
authors.affiliation: Centre for Reviews and Dissemination, University of York, York, United Kingdom; Department of Paediatric Oncology Haematology, Leeds General Infirmary, Leeds, United Kingdom.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Phillips
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Calapai
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000068818:Cetuximab / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced* / Q000453:epidemiology; D066246:ErbB Receptors / Q000276:immunology*; D006801:Humans; D015994:Incidence; D052016:Mucositis / Q000139:chemically induced* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Adverse events; Anti-egfr monoclonal antibodies; Cetuximab; Colorectal cancer; Diarrhoea; Meta-analysis; Mucositis; Panitumumab; Pharmacovigilance; Systematic review