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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 total incidence of all-grade diarrhea of patients with carcinomas receiving vandetanib.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 incidence of all-grade diarrhea. Since heterogeneity test indicated no heterogeneity, the total incidence of all-grade diarrhea was calculated using the fixed-effects model.Abbreviation: ES, effect size.
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f2-ott-9-3621: Forest plot of the total incidence of all-grade diarrhea of patients with carcinomas receiving vandetanib.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 incidence of all-grade diarrhea. Since heterogeneity test indicated no heterogeneity, the total incidence of all-grade diarrhea was calculated using the fixed-effects model.Abbreviation: ES, effect size.

Mentions: For the incidence analysis, we considered only arms receiving vandetanib 300 mg as a single agent. All-grade diarrhea was reported in all the 13 studies, with 1,964 patients treated by 300 mg vandetanib, and its incidence ranged from 42.11% in a randomized-controlled Phase II study of patients of hepatocellular carcinoma17 to 78.85% in another randomized-controlled Phase II study of patients of SCLC.23 Since the meta-analysis revealed no evidence of heterogeneity of the included studies (heterogeneity test, I2=18.7%, P=0.255), the fixed-effects model was applied. The calculated summary incidence of all-grade diarrhea was calculated to be 52.1% (95% CI, 48.3%–55.8%) (Figure 2).


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 total incidence of all-grade diarrhea of patients with carcinomas receiving vandetanib.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 incidence of all-grade diarrhea. Since heterogeneity test indicated no heterogeneity, the total incidence of all-grade diarrhea was calculated using the fixed-effects model.Abbreviation: ES, effect size.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ott-9-3621: Forest plot of the total incidence of all-grade diarrhea of patients with carcinomas receiving vandetanib.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 incidence of all-grade diarrhea. Since heterogeneity test indicated no heterogeneity, the total incidence of all-grade diarrhea was calculated using the fixed-effects model.Abbreviation: ES, effect size.
Mentions: For the incidence analysis, we considered only arms receiving vandetanib 300 mg as a single agent. All-grade diarrhea was reported in all the 13 studies, with 1,964 patients treated by 300 mg vandetanib, and its incidence ranged from 42.11% in a randomized-controlled Phase II study of patients of hepatocellular carcinoma17 to 78.85% in another randomized-controlled Phase II study of patients of SCLC.23 Since the meta-analysis revealed no evidence of heterogeneity of the included studies (heterogeneity test, I2=18.7%, P=0.255), the fixed-effects model was applied. The calculated summary incidence of all-grade diarrhea was calculated to be 52.1% (95% CI, 48.3%–55.8%) (Figure 2).

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