Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected].
OBJECTIVE
To compare survival in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with gefitinib 250 or 500 mg/day or standard methotrexate.


METHODS
Four hundred eighty-six patients with recurrent SCCHN were randomly assigned to oral gefitinib 250 mg/day, gefitinib 500 mg/day, or methotrexate 40 mg/m(2) intravenously weekly. Primary end point was overall survival, secondary end points were objective response rate (ORR), safety, symptom improvement, and quality of life (QOL). Exploratory end points included association of efficacy with epidermal growth factor receptor gene copy number and other biomarkers.


RESULTS
Neither gefitinib 250 nor 500 mg/day improved overall survival compared with methotrexate (hazard ratio [HR], 1.22; 95% CI, 0.95 to 1.57; P = .12; and HR, 1.12; 95% CI, 0.87 to 1.43; P = .39, respectively). In the gefitinib 250 mg/day, 500 mg/day, and methotrexate groups, respectively, median overall survival was 5.6, 6.0, and 6.7 months; ORRs (Response Evaluation Criteria in Solid Tumors) were 2.7%, 7.6% and 3.9%, with no statistically significant difference between either gefitinib arm and methotrexate. No unexpected adverse events were observed, except for tumor hemorrhage-type events with gefitinib (8.9%, gefitinib 250 mg/day; 11.4%, gefitinib 500 mg/day; 1.9%, methotrexate). QOL improvement rates (Functional Assessment of Cancer Therapy-Head & Neck total score) were 13.4%, 18.0%, and 6.0% for gefitinib 250 mg/day, 500 mg/day, and methotrexate, respectively.


CONCLUSIONS
In patients with recurrent or metastatic SCCHN, while responses with gefitinib were seen, neither gefitinib 250 nor 500 mg/day improved overall survival compared with methotrexate. With the exception of tumor hemorrhage-type events with gefitinib, the adverse event profiles were generally consistent with those previously observed.
Stewart
J Simon W
JS
Charing Cross Hospital, London, UK. s.stewart@imperial.ac.uk
Cohen
Ezra E W
EE
Licitra
Lisa
L
Van Herpen
Carla M L
CM
Khorprasert
Chonlakiet
C
Soulieres
Denis
D
Vodvarka
Pavel
P
Rischin
Danny
D
Garin
Avgust M
AM
Hirsch
Fred R
FR
Varella-Garcia
Marileila
M
Ghiorghiu
Serban
S
Hargreaves
Laura
L
Armour
Alison
A
Speake
Georgina
G
Swaisland
Alan
A
Vokes
Everett E
EE
D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage*; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib; D008727:Methotrexate