EXPRESSION OF EGFR AND P-AKT PROTEINS AS PREDICITIVE
FACTORS OF THERAPEUTIC RESPONSE TO ERLOTINIB COMBINED
WITH CISPLATIN AND RADIOTHERAPY IN LOCALLY ADVANCED
SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
Santos I C, MD, Herchenhorn D, MD, Dias F L, MD, Michaluart P, MD, Farias PA MD, Bernardo V,
Raposo D, Simão T, Santos P T, Pinto L F R, Costa ALA, MD.
Brazilian National Cancer Institute-INCA (MS/RJ)
PURPOSE
Erlotinib, an oral tyrosine-kinase inhibitor, is active against
squamous cell carcinoma of the head and neck (HNSCC) and
possibly has a synergistic interaction with chemotherapy and
radiotherapy. We investigated the expression of EGFR and
phosphorylated Akt by immunohistochemistry as predictors of
response to Erlotinib in a cohort of 27 locally advanced HNSCC,
enrolled in a Phase II trial. In addition, we assessed mutations on
hotspots of EGFR gene (exons18,19,20,21).
PATIENTS AND METHODS
Figure 2: Electropherogram without mutations of exons 18,19,20,21
EGFR
> 38.8
< 38.8
Months
p-Akt
RESULTS
> 22.8
< 22.8
Response to therapy was evident in 20 (62.5%) patients. Neither
EGFR nor p-Akt predicted for overall survival. Mutations were not
found on hotspots of EGFR gene.
Months
Figure 3: Results of Immunohistochemistry of EGFR and p-Akt
CONCLUSION
Additional biomarker studies with larger sample sizes are required to
elucidate HNSCC patients who may benefit from this targeted therapy.
Figure 1: Slides from the same patient showing (A) EGFR and (B) p-Akt immunostaining. (Scale
bars: 100m
m)
Keywords: chemotherapy; epidermal growth factor receptor;
erlotinib; head and neck neoplasms; radiotherapy; squamous cell
carcinoma
Projeto Gráfico: Serviço de Edição e Informação Técnico-Científica / INCA
This study was conducted in a Phase I/II trial of cisplatin 100
mg/m2 on days 8, 29 and 50; and radiotherapy 70.2 Gy starting on
day 8. Erlotinib was started orally 1 week before chemo radiation
and continued daily until the last day of chemo radiation.
Pretreatment archival tumor specimens were evaluated for EGFR
and phosphorylated-Akt (p-Akt) by immunohistochemistry. These
immunostains were quantified by digital image analysis. EGFR
gene mutational status was also assessed using conventional PCR
and sequencing.