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Supportive Care in Cancer
Published in: Supportive Care in Cancer 6/2015

01-06-2015 | Original Article

Tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR) have distinct cutaneous toxicity profiles: a meta-analysis and review of the literature

Authors: Paul R. Massey, Jonathan S. Okman, Julia Wilkerson, Edward W. Cowen

Published in: Supportive Care in Cancer | Issue 6/2015

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Abstract

Purpose

Inhibition of the vascular endothelial growth factor 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 trials.

Methods

PubMed was queried for phase II or III trials of anti-VEGFR TKIs between 2000 and 2013 involving ≥50 patients. Adverse events were abstracted, with results presented in both fixed and random effects models. Odds ratios (OR) and 95 % confidence intervals (CIs) were estimated for studies with at least two arms.

Results

Across 82 included studies, all grades rash (OR, 2.68; 95 % CI, 2.45–2.94), hand-foot skin reaction (HFSR) (OR, 2.70; 95 % CI, 2.43–3.00), and pruritus (OR, 1.25; 95 % CI, 1.12–1.39) were associated with anti-VEGFR TKIs. Vandetanib had 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 trend (r 2 = 0.042, p = 0.10) and in sunitinib therapy increased significantly (r 2 = 0.237, p = 0.04).

Conclusion

The incidence of HFSR, rash, and pruritus varies considerably by drug. Our data suggest a continued need to address skin toxicities and improve reporting strategies.
Appendix
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Metadata
Title
Tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR) have distinct cutaneous toxicity profiles: a meta-analysis and review of the literature
Authors
Paul R. Massey
Jonathan S. Okman
Julia Wilkerson
Edward W. Cowen
Publication date
01-06-2015
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 6/2015
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-014-2520-9

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