title: A systematic review and meta-analysis of the risk of diarrhea associated with vandetanib treatment in carcinoma patients.
abstract: OBJECTIVE
  Vandetanib is a promising anticancer targeted agent for treating advanced carcinomas, such as non-small-cell lung cancer, small-cell lung cancer, breast cancer, malignant glioma, hepatocellular cancer, and unresectable, locally advanced, or metastatic medullary thyroid cancer. However, diarrhea is a frequently reported adverse event. The incidence of vandetanib-associated diarrhea varies extensively in different study populations and has not been carefully estimated. This systematic review and meta-analysis of clinical trials aims to figure out the overall risks of all-grade and high-grade diarrhea during vandetanib treatment and get a better understanding of its prediction and management.
  
  
  METHODS
  A comprehensive search was performed in EMBASE, PubMed, and Cochrane Library for clinical trials studying vandetanib and diarrhea prior to April 2015. Eligible articles were selected according to the inclusion criteria. Data were extracted to calculate the summary incidence of all-grade and high-grade diarrhea caused by vandetanib treatment.
  
  
  RESULTS
  Thirteen clinical trials that involved 3,264 patients were included in this meta-analysis. The overall incidences of all-grade and high-grade diarrhea caused by vandetanib treatment were 52.1% (95% confidence interval [CI], 48.3%-55.8%) and 5.6% (95% CI, 4.4%-76.7%), respectively. The risk ratios of the all-grade and high-grade diarrhea for vandetanib arm versus control arm were 1.932 (95% CI, 1.746-2.138; P<0.001) and 3.190 (95% CI, 2.061-4.938; P<0.001), respectively. Studies with small-cell lung cancer demonstrated the highest incidence of all-grade diarrhea (78.85%) and high-grade diarrhea (17.31%), whereas the lowest incidences of all-grade (42.11%) and high-grade (2.67%) diarrhea are seen in patients with hepatocellular carcinoma and non-small-cell lung cancer, respectively.
  
  
  CONCLUSIONS
  Our findings demonstrate that the administration of vandetanib leads to a significantly increased risk of diarrhea, which varies in different carcinoma patients. Early recognition and timely management may be key factors to avoid dose reduction, drug interruption, and drug discontinuation, which is significant to maximize the treatment benefits.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zijun
authors.initials: Z
authors.lastname: Huo
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Shubin
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Xiu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Xiao
keywords: carcinoma; diarrhea; vandetanib treatment