Phase II study of sunitinib malate in head and neck squamous cell carcinoma.
BACKGROUND
Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor of RET, VEGFR, PDGFR, and c-KIT. We conducted a phase II trial to evaluate the tolerability and efficacy of sunitinib in metastatic and/or recurrent SCCHN patients.


METHODS
Patients who had received no more than two prior chemotherapy regimens were eligible and, depending on ECOG performance status (PS), were entered into either Cohort A (PS 0-1) or Cohort B (PS 2). Sunitinib was administered in 6-week cycles at 50 mg daily for 4 weeks followed by 2 weeks off. Primary endpoint for Cohort A was objective tumor response. A Simon two-stage design required twelve patients to be enrolled in the first stage and if 1 or fewer responses were observed, further study of this cohort would be terminated due to lack of treatment efficacy. Primary endpoint of Cohort B was to determine the feasibility of sunitinib in patients with ECOG performance status 2.


RESULTS
Twenty-two patients were accrued (Cohort A - 15 patients, Cohort B - 7 patients). Median age in cohort A and B was 56 and 61 years, respectively. Grade 3 hematologic toxicities encountered were lymphopenia (18%), neutropenia (14%) and thrombocytopenia (5%). There was only one incidence of grade 4 hematologic toxicity which was thrombocytopenia. Fatigue and anorexia were the most common non-hematologic toxicities. Grade 3 fatigue occurred in 23% of patients. The only grade 4 non-hematologic toxicity was one incidence of gastrointestinal hemorrhage. Non-fatal hemorrhagic complications occurred in 8 patients: epistaxis (3 patients), pulmonary hemorrhage (2 patients), gastrointestinal hemorrhage (2 patients) and tumor hemorrhage (1 patient). Four patients were not evaluable for tumor response (Cohort A - 3patients, Cohort B - 1 pt). One partial response was observed in the entire study. Dose reduction was required in 5 patients (Cohort A - 3 patients for grd 3 fatigue, grd 3 mucositis and recurrent grd 3 neutropenia; Cohort B - 2 patients for grd 3 fatigue and grd 3 nausea). Median time to progression for cohort A and B were 8.4 and 10.5 weeks, respectively. Median overall survival for cohort A and B was 21 and 19 weeks, respectively.


CONCLUSIONS
Sunitinib had low single agent activity in SCCHN necessitating early closure of cohort A at interim analysis. Sunitinib was well tolerated in PS 2 patients. Further evaluation of single agent sunitinib in head and neck is not supported by the results of this trial.
Choong
Nicholas W
NW
Section of Hematology-Oncology and Phase II network, University of Chicago Medical Center, S. Maryland Avenue, Chicago, IL 60637, USA. nchoong@mcw.edu
Kozloff
Mark
M
Taber
David
D
Hu
H Shawn
HS
Wade
James
J
Ivy
Percy
P
Karrison
Theodore G
TG
Dekker
Allison
A
Vokes
Everett E
EE
Cohen
Ezra E W
EE
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003710:Demography; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib