Pilot study of neoadjuvant treatment with erlotinib in nonmetastatic head and neck squamous cell carcinoma.
OBJECTIVE
To determine the safety and efficacy of erlotinib given as neoadjuvant treatment in patients with head and neck squamous cell carcinoma (HNSCC). Further objectives were to identify markers of response to erlotinib and to assess the pharmacodynamic effects of erlotinib in tumor cells.


METHODS
Patients with locally advanced nonmetastatic HNSCC were treated with erlotinib 150 mg daily pending surgical management. Tumor samples were collected before and after erlotinib treatment and were analyzed using immunohistochemistry. Epidermal growth factor receptor copy number was determined in tumors using CISH analysis.


RESULTS
Between November 2003 and December 2005, 35 patients were included in the study. Neoadjuvant treatment with erlotinib in HNSCC patients was well tolerated and did not necessitate modification to routine surgical procedures. Among 31 evaluable patients, erlotinib was given for a median of 20 days. At the time of surgery, tumor shrinkage was observed in nine patients (29%). Immunohistochemistry analyses were done for 31 patients and showed a decrease in phosphorylated tyrosine residues and phosphorylated erk immunostaining after erlotinib treatment. In a retrospective analysis, baseline p21(waf) expression in the basal-like cell layer was statistically positively correlated with clinical response to treatment. Epidermal growth factor receptor copy number did not correlate with response to erlotinib.


CONCLUSIONS
Neoadjuvant treatment of HNSCC with erlotinib was well tolerated. Baseline p21(waf) expression was associated with response to erlotinib and so might be useful as a tool to select patients for erlotinib therapy in this setting.
Thomas
Fabienne
F
Laboratoire de Pharmacologie Clinique et Expérimentale des Médicaments Anticancéreux, EA3035, Institut Claudius Regaud, Université Paul Sabatier, France.
Rochaix
Philippe
P
Benlyazid
Adil
A
Sarini
Jérôme
J
Rives
Michel
M
Lefebvre
Jean Louis
JL
Allal
Ben C
BC
Courbon
Frédéric
F
Chatelut
Etienne
E
Delord
Jean-Pierre
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors