Toxicity of targeted therapy: Implications for response and impact of genetic polymorphisms.

Abstract:

:Targeted therapies have unique toxicity profiles. Common adverse events include rash, diarrhea, hypertension, hypothyroidism, proteinuria, depigmentation, and hepatotoxicity. Some of these toxicities are caused by on-target, mechanism-associated effects, which can be stratified as to whether or not the targets are relevant to response. Other toxicities are off-target and may be caused by the class of agent, e.g. antibody vs small molecule tyrosine kinase inhibitor, or by immune reactions or toxic metabolites. Both on- and off-target toxicities may be due to higher drug concentrations or altered end-organ sensitivity, which in turn can be a consequence of genetic polymorphisms controlling metabolism or tissue responsiveness. On-target toxicities are important to identify as some correlate with response and, hence, amelioration of these side effects is preferable to dose reduction or stopping drug. Toxicities secondary to relevant target impact may be recognized when distinct types of agents, such as antibodies and small molecule kinase inhibitors, with the same target have a similar side effect. For example, both bevacizumab and vascular endothelial growth factor receptor (VEGFR) kinase inhibitors cause hypertension; both epidermal growth factor receptor (EGFR) antibodies and kinase inhibitors cause rash; and these toxicities correlate with response. Herein we review common targeted agent-related toxicities, relevant genetic polymorphisms, and implications for response and patient management.

journal_name

Cancer Treat Rev

journal_title

Cancer treatment reviews

authors

Liu S,Kurzrock R

doi

10.1016/j.ctrv.2014.05.003

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

883-91

issue

7

eissn

0305-7372

issn

1532-1967

pii

S0305-7372(14)00088-7

journal_volume

40

pub_type

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