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Epidermal Growth Factor Receptor
Tyrosine Kinase Inhibitors: Evolving Role
in the Treatment of Solid Tumors
Peggy Krozely, RN, BSN
ince the 1980s, the
Targeting
Inhibitors of epidermal growth factor receptor tyrosine
search for new anticanEpidermal Growth
cer therapies has benkinase (EGFR-TK) activity have shown promise as novel
efited from advances in the unFactor Receptors
anticancer agents in a variety of common solid tumors.
derstanding of tumor biology and
In preclinical studies and phase I trials, tumor responses
EGFR-TK plays a pivotal
the genetics of cancer. A variety
role in the development of
to EGFR-TK inhibitors (EGFR-TKIs), such as gefitinib
of agents has been discovered
many of the most common solid
(e.g., targeted therapies) that stop
(Iressa® , AstraZeneca Pharmaceuticals LP, Wilmington,
tumors (Dy & Adjei, 2002; Prentumor growth by inhibiting speDE) and erlotinib (TarcevaTM, OSI Pharmaceuticals, Melzel, Fischer, Streit, Hart, & Ullcific molecular targets in tumors.
ville, NY, and Genentech, Inc., South San Francisco, CA)
rich, 2001; Raymond et al., 2000).
These target molecules are esEGFR, also known as ErbB1 or
sential to the growth and progreswere observed in heavily pretreated patients with adHER1, is present in most cell
sion of tumors but are not
vanced non-small cell lung cancer (NSCLC), head and
types, with the exception of heneeded in normal tissues (Kelloff
neck cancer, breast cancer, colorectal cancer, and other
matopoietic cells. Under normal
et al., 1996; Raymond, Faivre, &
circumstances, EGFR-TK signalsolid tumors. Subsequent phase II studies resulted in tuArmand, 2000). This is in coning is controlled strictly. In tumor
trast to cytotoxic chemotherapy
mor responses, disease stabilization, symptom improvecells, however, normal regulaagents that do not discriminate
ment, and improved quality of life in patients with adtions that limit EGFR-TK enbetween killing proliferating tuvanced NSCLC who had received prior platinum-based
zyme activity and the subsemor cells and normal cells and
quent transduction of growth
chemotherapy or platinum and docetaxel chemotheramay lead to severe or debilitatsignals are lost. A variety of tuing drug-related toxicities. The
pies. Side effects related to treatment with EGFR-TKIs
mor cell responses results from
goal for targeted therapies is to
were generally mild, reversible, and noncumulative. Seaberrantly activated EGFR-TK,
provide antitumor benefits with
verity
and
frequency
of
drug-related
adverse
events
were
including stimulation of cell
better tolerability.
growth, promotion of cell motilThe epidermal growth factor
related directly to dose. The potential role of EGFR-TKIs
ity, alteration of adhesion and
receptor tyrosine kinase (EGFRin treating other solid tumors currently is being studied.
invasiveness, prolongation of
TK) is one key target molecule
Furthermore,
research
is
being
conducted
to
explore
the
cell survival, and stimulation of
in tumor cells that is responsible
angiogenesis (Herbst & Shin,
potential use of EGFR-TKIs in novel combinations with
for activating multiple downstream signaling pathways govchemotherapy, radiation therapy, endocrine therapy, and
erning tumor growth. Clinical
other molecular targeted therapies.
Submitted August 2003. Actrials of targeted EGFR-TK incepted for publication October 8,
hibitors (EGFR-TKIs) have
Key Words: carcinoma, non-small-cell lung; receptor,
2003. (Mention of specific proddemonstrated benefits in paepidermal growth factor
ucts
and opinions related to
tients with advanced solid tuthose
products do not indicate or
mors and have been associated
with unique clinical features and safety or for patients who cannot tolerate the tox- imply endorsement by the Clinical Journal of
profiles compared with conventional cyto- icity associated with chemotherapy. Strat- Oncology Nursing or the Oncology Nursing
toxic therapies. Molecular targeted thera- egies for incorporating EGFR-TKIs into Society.) Peggy Krozely, RN, BSN, has served
to AstraZeneca, manufacturer
pies, such as EGFR-TKIs, may provide im- treatment plans for patients with solid ma- as a consultant
®
portant treatment options for patients with lignancies are evolving, and their optimal of Iressa (gefitinib), which is mentioned in
advanced solid tumors whose disease has use represents an active area of clinical re- this article.
progressed while receiving chemotherapy search.
Digital Object Identifier: 10.1188/04.CJON.163-168
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CLINICAL JOURNAL OF ONCOLOGY NURSING • VOLUME 8, NUMBER 2 • EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITORS
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