Abstract
Chemotherapy continues to play an essential role in the treatment of most stages of non-small-cell lung cancer (NSCLC). In fact, within the past 5 years, this role has greatly expanded into adjuvant therapy for early-stage resected disease. Likewise, agents targeting the epidermal growth factor receptor (EGFR), particularly the tyrosine kinase inhibitors gefitinib and erlotinib, have proven to be clinically active in patients with advanced-stage NSCLC. Because of these findings, it is logical to expect that combinations of these 2 classes of antineoplastic agents would prove more efficacious than either one alone. Yet 4 large randomized phase III trials of chemotherapy with or without an EGFR tyrosine kinase inhibitor in unselected patients with advanced-stage NSCLC, altogether totaling > 4000 patients, did not demonstrate improvement in clinical outcomes with the combination. Whether these negative results will be reproduced in ongoing combination studies of chemotherapy plus monoclonal antibodies directed against EGFR remain to be determined. Herein, we review recent preclinical and clinical data addressing this topic and explore the biologic rationale for developing new combination strategies based on patient selection by molecular and clinical factors, or by pharmacodynamic parameters.
| Original language | English (US) |
|---|---|
| Journal | Clinical Lung Cancer |
| Volume | 8 |
| Issue number | SUPPL. 2 |
| DOIs | |
| State | Published - Feb 2007 |
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Keywords
- Antineoplastic agents
- Monoclonal antibodies
- Tyrosine kinase inhibitors
ASJC Scopus subject areas
- Cancer Research
- Pulmonary and Respiratory Medicine
Cite this
Epidermal growth factor receptor inhibitors plus chemotherapy in non-small-cell lung cancer : Biologic rationale for combination strategies. / Gandara, David R; Davies, Angela M.; Gautschi, Oliver; Mack, Philip; Lau, Derick H; Lara, Primo N; Hirsch, Fred R.
In: Clinical Lung Cancer, Vol. 8, No. SUPPL. 2, 02.2007.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epidermal growth factor receptor inhibitors plus chemotherapy in non-small-cell lung cancer
T2 - Biologic rationale for combination strategies
AU - Gandara, David R
AU - Davies, Angela M.
AU - Gautschi, Oliver
AU - Mack, Philip
AU - Lau, Derick H
AU - Lara, Primo N
AU - Hirsch, Fred R.
PY - 2007/2
Y1 - 2007/2
N2 - Chemotherapy continues to play an essential role in the treatment of most stages of non-small-cell lung cancer (NSCLC). In fact, within the past 5 years, this role has greatly expanded into adjuvant therapy for early-stage resected disease. Likewise, agents targeting the epidermal growth factor receptor (EGFR), particularly the tyrosine kinase inhibitors gefitinib and erlotinib, have proven to be clinically active in patients with advanced-stage NSCLC. Because of these findings, it is logical to expect that combinations of these 2 classes of antineoplastic agents would prove more efficacious than either one alone. Yet 4 large randomized phase III trials of chemotherapy with or without an EGFR tyrosine kinase inhibitor in unselected patients with advanced-stage NSCLC, altogether totaling > 4000 patients, did not demonstrate improvement in clinical outcomes with the combination. Whether these negative results will be reproduced in ongoing combination studies of chemotherapy plus monoclonal antibodies directed against EGFR remain to be determined. Herein, we review recent preclinical and clinical data addressing this topic and explore the biologic rationale for developing new combination strategies based on patient selection by molecular and clinical factors, or by pharmacodynamic parameters.
AB - Chemotherapy continues to play an essential role in the treatment of most stages of non-small-cell lung cancer (NSCLC). In fact, within the past 5 years, this role has greatly expanded into adjuvant therapy for early-stage resected disease. Likewise, agents targeting the epidermal growth factor receptor (EGFR), particularly the tyrosine kinase inhibitors gefitinib and erlotinib, have proven to be clinically active in patients with advanced-stage NSCLC. Because of these findings, it is logical to expect that combinations of these 2 classes of antineoplastic agents would prove more efficacious than either one alone. Yet 4 large randomized phase III trials of chemotherapy with or without an EGFR tyrosine kinase inhibitor in unselected patients with advanced-stage NSCLC, altogether totaling > 4000 patients, did not demonstrate improvement in clinical outcomes with the combination. Whether these negative results will be reproduced in ongoing combination studies of chemotherapy plus monoclonal antibodies directed against EGFR remain to be determined. Herein, we review recent preclinical and clinical data addressing this topic and explore the biologic rationale for developing new combination strategies based on patient selection by molecular and clinical factors, or by pharmacodynamic parameters.
KW - Antineoplastic agents
KW - Monoclonal antibodies
KW - Tyrosine kinase inhibitors
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UR - http://www.scopus.com/inward/citedby.url?scp=34147105416&partnerID=8YFLogxK
U2 - 10.3816/CLC.2007.s.003
DO - 10.3816/CLC.2007.s.003
M3 - Article
C2 - 17382026
AN - SCOPUS:34147105416
VL - 8
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
SN - 1525-7304
IS - SUPPL. 2
ER -