Phase II trial of sorafenib in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or nasopharyngeal carcinoma.
OBJECTIVE
To determine the efficacy and safety of single-agent sorafenib in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and nasopharyngeal carcinoma (NPC).


METHODS
In this single-arm phase II trial, oral continuous sorafenib was administered in 28-day cycles. Patients had <or= one line of chemotherapy for recurrent and/or metastatic disease, Eastern Cooperative Oncology Group performance status of <or= 2, and adequate organ function. At the end of stage 1, efficacy criteria for further accrual were not met, but the study was amended to enroll an additional five patients for paired tumor biopsies.


RESULTS
Twenty-seven and 26 patients were eligible for toxicity and efficacy evaluations, respectively. One patient (3.7%; 95% CI, 0.1% to 19.0%) achieved a partial response. Disease stabilization was maintained in 10 patients (37.0%; 95% CI, 22.4% to 61.2%). The median time to progression was 1.8 months (95% CI, 1.6 to 3.4 months), and median overall survival time was 4.2 months (95% CI, 3.6 to 8.7 months). Sorafenib was well tolerated with few grade 3 and no grade 4 toxicities. Biomarker analysis of paired tumor samples before and after treatment with sorafenib revealed a decrease of pERK in all five patients, with a decrease in Ki67 in four patients, consistent with a disruption of ERK signaling. The antiapoptotic protein Mcl-1 was downregulated in four patients, and there was also evidence of antiangiogenic activity.


CONCLUSIONS
Sorafenib was well tolerated and had modest anticancer activity comparable to monotherapy with other targeted agents in this group of patients. Further development in combination with radiation or other agents may be warranted.
Elser
Christine
C
Princess Margaret Hospital, University Health Network, Department of Medical Oncology and Hematology, Toronto, Ontario, Canada.
Siu
Lillian L
LL
Winquist
Eric
E
Agulnik
Mark
M
Pond
Gregory R
GR
Chin
Soo F
SF
Francis
Peggy
P
Cheiken
Robin
R
Elting
James
J
McNabola
Angela
A
Wilkie
Dean
D
Petrenciuc
Oana
O
Chen
Eric X
EX
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use*; D000077157:Sorafenib; D015996:Survival Rate; D048490:raf Kinases / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048490:raf Kinases