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SEQUENCE DEPENDENCE OF CELL GROWTH INHIBITION BY EGFR–TYROSINE KINASE INHIBITOR ZD1839, DOCETAXEL, AND CISPLATIN IN HEAD AND NECK CANCER

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Author(s)
Carmen M. KlassMi Sun ChoeSelwyn J. HurwitzMourad TighiouartXin ZhangZhuo (Georgia) ChenDong M. Shin
Keimyung Author(s)
Choe, Mi Sun
Department
Dept. of Pathology (병리학)
Journal Title
Head & Neck
Issued Date
2009
Volume
31
Issue
10
Abstract
Background. This study was to explore whether
the efficacy of the epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitor ZD1839 (Z, Iressa, gefitinib) plus
chemotherapeutic agents docetaxel (D) and cisplatin (P) may
benefit from sequencing of the combination.
Methods. Three head and neck cancer cell lines were
used to study the effect of various combinations of and relative
sequencing of D, P, and Z in cell growth inhibition. A popula-
tion pharmacokinetic stimulation study was conducted on Z
in silico and used together with the growth inhibition data to
derive principles for future in vivo use of this drug
combination.
Results. The inhibitory effects of Z on combinations of D
and P were sequence dependent. Treatment simultaneously
with DPZ or with DP followed by Z (DP!Z) showed synergistic
effects in all 3 cell lines. However, sequencing with Z followed
by DP (Z!DP), gave an antagonistic effect, suggesting that D
and P should be administered when the effect of Z is low. The
induction of apoptosis was also sequence dependent. The in
silico pharmacokinetic study suggested the feasibility of deriv-
ing a 5-day-on/2-day-off regimen for Z, in which D and P
administration commences when levels of Z are low, allowing
levels of Z to accumulate sufficiently during the remainder of
the cycle.
Conclusion. These data suggests that it is feasible to
design clinical trials with these settings to maximize the effi-
cacy of this combined drug regimen.
V
V
C
2009 Wiley Periodi-
cals, Inc. Head Neck 31: 1263–1273, 2009
Keywords: EGFR; cytotoxic agent; docetaxel; cisplatin;
apoptosis; head and neck cancer
Keimyung Author(s)(Kor)
최미선
Publisher
School of Medicine
Citation
Carmen M. Klass et al. (2009). SEQUENCE DEPENDENCE OF CELL GROWTH INHIBITION BY
EGFR–TYROSINE KINASE INHIBITOR ZD1839, DOCETAXEL,
AND CISPLATIN IN HEAD AND NECK CANCER. Head & Neck, 31(10), 1263–1273. doi: 10.1002/hed.21103
Type
Article
ISSN
1043-3074
Source
https://onlinelibrary.wiley.com/doi/full/10.1002/hed.21103
DOI
10.1002/hed.21103
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35809
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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