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A systematic review and meta-analysis of the risk of diarrhea associated with vandetanib treatment in carcinoma patients.

Huo Z, Yu S, Hong S, Cao X, Xiu L, Liao Z, Li Y, Xiao H - Onco Targets Ther (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.

ABSTRACT

Background and purpose: 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.

Materials and 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Forest plot of the relative risk (RR) of all-grade diarrhea events.Notes: The size of the gray square corresponded to the weight of the study in the meta-analysis. The horizontal line represented the 95% confidence interval (CI) and the vertical dotted line showed the total RR of all-grade diarrhea.
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f4-ott-9-3621: Forest plot of the relative risk (RR) of all-grade diarrhea events.Notes: The size of the gray square corresponded to the weight of the study in the meta-analysis. The horizontal line represented the 95% confidence interval (CI) and the vertical dotted line showed the total RR of all-grade diarrhea.

Mentions: There are eight comparative clinical trials in total, which include six trials using placebo as controls, one using erlotinib, and one using gefitinib. Subjects in the vandetanib arm were at a significantly higher risk for all-grade diarrhea than subjects in the control arm (relative risk =1.932; 95% CI, 1.746–2.138; P<0.001) (Figure 4), with the use of the random-effects model (heterogeneity test, I2=90.9%, P<0.001). Seven out of these eight clinical trials provide data of high-grade diarrhea. Subjects in the vandetanib group were at a notably greater risk for high-grade diarrhea than subjects in the control arm (relative risk =3.190; 95% CI, 2.061–4.938, P<0.001) (Figure 5), with the application of the random-effects model (heterogeneity test, I2=59.5%, P=0.022).


A systematic review and meta-analysis of the risk of diarrhea associated with vandetanib treatment in carcinoma patients.

Huo Z, Yu S, Hong S, Cao X, Xiu L, Liao Z, Li Y, Xiao H - Onco Targets Ther (2016)

Forest plot of the relative risk (RR) of all-grade diarrhea events.Notes: The size of the gray square corresponded to the weight of the study in the meta-analysis. The horizontal line represented the 95% confidence interval (CI) and the vertical dotted line showed the total RR of all-grade diarrhea.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4920236&req=5

f4-ott-9-3621: Forest plot of the relative risk (RR) of all-grade diarrhea events.Notes: The size of the gray square corresponded to the weight of the study in the meta-analysis. The horizontal line represented the 95% confidence interval (CI) and the vertical dotted line showed the total RR of all-grade diarrhea.
Mentions: There are eight comparative clinical trials in total, which include six trials using placebo as controls, one using erlotinib, and one using gefitinib. Subjects in the vandetanib arm were at a significantly higher risk for all-grade diarrhea than subjects in the control arm (relative risk =1.932; 95% CI, 1.746–2.138; P<0.001) (Figure 4), with the use of the random-effects model (heterogeneity test, I2=90.9%, P<0.001). Seven out of these eight clinical trials provide data of high-grade diarrhea. Subjects in the vandetanib group were at a notably greater risk for high-grade diarrhea than subjects in the control arm (relative risk =3.190; 95% CI, 2.061–4.938, P<0.001) (Figure 5), with the application of the random-effects model (heterogeneity test, I2=59.5%, P=0.022).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.

ABSTRACT

Background and purpose: 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.

Materials and 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus