Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib

Authors

Lokesh Jain, Virginia Commonwealth University
Tristan M. Sissung, National Cancer Institute
Romano Danesi, University of Pisa
Elise C. Kohn, National Cancer Institute
William L. Dahut, National Cancer Institute
Shivaani Kummar, National Cancer Institute
David Venzon, National Cancer Institute
David Liewehr, National Cancer Institute
Bevin C. English, National Cancer Institute
Caitlin E. Baum, National Cancer Institute
Robert Yarchoan, National Cancer Institute
Guiseppe Giaccone, National Cancer Institute
Jurgen Venitz, Virginia Commonwealth University
Douglas K. Price, National Cancer Institute
William D. Figg, National Cancer Institute

Document Type

Article

Original Publication Date

2010

Journal/Book/Conference Title

Journal of Experimental & Clinical Cancer Research

DOI of Original Publication

10.1186/1756-9966-29-95

Comments

Originally published at http://dx.doi.org/10.1186/1756-9966-29-95

Date of Submission

August 2014

Abstract

Background Hypertension (HT) and hand-foot skin reactions (HFSR) may be related to the activity of bevacizumab and sorafenib. We hypothesized that these toxicities would correspond to favorable outcome in these drugs, that HT and HFSR would coincide, and that VEGFR2 genotypic variation would be related to toxicity and clinical outcomes.

Methods Toxicities (≥ grade 2 HT or HFSR), progression-free survival (PFS), and overall survival (OS) following treatment initiation were evaluated. Toxicity incidence and VEGFR2 H472Q and V297I status were compared to clinical outcomes.

Results Individuals experiencing HT had longer PFS following bevacizumab therapy than those without this toxicity in trials utilizing bevacizumab in patients with prostate cancer (31.5 vs 14.9 months, n = 60, P = 0.0009), and bevacizumab and sorafenib in patients with solid tumors (11.9 vs. 3.7 months, n = 27, P = 0.052). HT was also linked to a > 5-fold OS benefit after sorafenib and bevacizumab cotherapy (5.7 versus 29.0 months, P = 0.0068). HFSR was a marker for prolonged PFS during sorafenib therapy (6.1 versus 3.7 months respectively, n = 113, P = 0.0003). HT was a risk factor for HFSR in patients treated with bevacizumab and/or sorafenib (OR(95%CI) = 3.2(1.5-6.8), P = 0.0024). Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136).

Conclusions This study suggests that HT and HFSR may be markers for favorable clinical outcome, HT development may be a marker for HFSR, and VEGFR2 alleles may be related to the development of toxicities during therapy with bevacizumab and/or sorafenib.

Rights

© 2010 Jain et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Is Part Of

VCU Pharmaceutics Publications