When missing data were experienced, FDA package inserts were used as well mainly because the adverse events listing in the Effects tab of clinicaltrials.gov. diarrhea marks 1/2 (G), diarrhea Racecadotril (Acetorphan) marks 3/4 (H). Supplemental Fig 3. Additional Time Interval Scatter Plots Separated by Adverse Events Grade. Additional time interval scatter plots for rates of adverse events in individuals taking sunitinib and sorafenib, structured by low grade (1/2) and high grade (3/4) HFSR and diarrhea. Supplemental Fig 4ACD. Additional Subgroup Analysis of Monotherapy v. Combination Therapy By Drug. Forest plots of randomized tests demonstrating odds percentage for going through all grade rash (A), all grade HFSR (B), all grade pruritus (C), or all grade diarrhea (D), structured by drug and relating to whether drug was given as monotherapy or in combination with standard cytotoxic chemotherapy. Supplemental Table 1. Summary Table of Included Studies. Summary table of 82 tests meeting inclusion criteria including treatment, author name, yr of publication, dose of drug, quantity of individuals and if randomization or use of placebo were present. NIHMS646820-product-520_2014_2520_MOESM1_ESM.pdf (1.9M) GUID:?80BE3283-41EB-43EF-A346-B0C224E9E55B Abstract Purpose Inhibition of the vascular endothelial growth element receptor (VEGFR) with tyrosine kinase inhibitors (TKIs) is associated with cutaneous adverse effects that increase patient morbidity. Our objective was to examine the skin toxicity profile of anti-VEGFR TKIs and determine the changing incidence in clinical tests. Methods PubMed was queried for Phase II or III tests of anti-VEGFR TKIs between 2000 and 2013 including 50 individuals. Adverse events were abstracted, with results offered in both fixed and random effects models. Odds ratios (OR) and 95% CIs were estimated for studies with at least two arms. Results Across 82 included studies, all Racecadotril (Acetorphan) marks rash (OR, 2.68; 95% CI, 2.45C2.94), hand foot pores and skin reaction (HFSR) Racecadotril (Acetorphan) (OR, 2.70; 95% CI, 2.43C3.00) and pruritus (OR, 1.25; 95% CI, 1.12C1.39) were associated with anti-VEGFR TKIs. Vandetanib experienced the highest incidence of rash (41%), while sorafenib was most commonly associated with HFSR (37%) and pruritus (14%). The incidence of HFSR from 2000 to 2013 showed an upward tendency (r2=0.042, p=0.10) and in sunitinib therapy increased significantly (r2=0.237, p=0.04). Summary The incidence of HFSR, rash and pruritus varies substantially by Racecadotril (Acetorphan) drug. Our data suggest a continued need to address pores and skin toxicities and improve reporting strategies. multikinase inhibition profiles. MATERIAL AND METHODS Data Sources A PubMed search was performed for content articles published between January 2000 and March 2013 using common drug titles and unique designations (e.g. BAY734506) as keywords. When missing data were encountered, FDA package inserts were used as well as the adverse events listing in the Results tab of clinicaltrials.gov. Where adverse event data were reported below a particular threshold percentage, data were entered into the database as threshold % – 1% (e.g. if authors reported HFSR occurred in 10% of subjects, a value of 9% was came into for that adverse event). Study Selection The following inclusion criteria were applied to all identified medical studies: 1) published in English; 2) Phase II or III trial; 3) 50 individuals in the security analysis; 4) 50 individuals in the dose arm or routine for that particular arm to be included. A minimum of 50 individuals per study or treatment arm was used to limit the number of small tests. If one study arm met access criteria but another did not, the arm with 50 individuals was omitted. Data Extraction Trials were reviewed individually by two study authors (P.M. and J.O.). The following data elements were abstracted: treatment, human population under study, dose, administration method and schedule, yr of publication, median day of individual enrollment, region of study, trial phase, trial design, quantity of individuals on study and Fgfr1 quantity of individuals evaluated in the security analysis. Adverse events data included HFSR, pruritus, rash, diarrhea, fatigue, quantity of individuals who discontinued the trial and quantity who underwent dose reductions. Statistical Analysis Meta-analyses were performed on randomized studies that compared anti-VEGFR TKI therapy having a non-anti-VEGFR TKI therapy. For studies with more than two arms, each unique experimental/control arm combination was treated as a separate entry. The summary measure utilized for the pooling of studies in fixed effects (weighted with inverse variance) meta-analyses was an odds ratio (OR) and the DerSimonian-Laird method was used to estimate the between-study variance. A level of 0.95 was.