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

Crit Rev Oncol Hematol. 2015 Nov;96(2):355-71. doi: 10.1016/j.critrevonc.2015.06.004. Epub 2015 Jun 24.

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.

Keywords: Adverse events; Anti-egfr monoclonal antibodies; Cetuximab; Colorectal cancer; Diarrhoea; Meta-analysis; Mucositis; Panitumumab; Pharmacovigilance; Systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Cetuximab / adverse effects
  • Colorectal Neoplasms / drug therapy*
  • Diarrhea / chemically induced*
  • Diarrhea / epidemiology
  • ErbB Receptors / immunology*
  • Humans
  • Incidence
  • Mucositis / chemically induced*
  • Mucositis / epidemiology
  • Randomized Controlled Trials as Topic
  • Risk

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab