Prognostic significance of p16 in locoregionally advanced head and neck             cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity-modulated             radiation therapy.
A phase II trial was conducted to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) into a well-described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Patients with stage IVa-IVb or high-risk stage III squamous cell carcinomas were enrolled. Prior organ-conserving surgery or induction chemotherapy was allowed. IMRT was administered in 1.5 Gy fractions twice daily on days 1-5 of weeks 1, 3, 5, 7±9 for a total dose of 60-73.5 Gy. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg BID) and cetuximab (250 mg/m2). p16INK4A expression was assessed by immunohistochemistry. From January 2007 to January 2010, 65 patients (61 with stage IV disease; 31 with oropharyngeal primaries) were enrolled. At a median follow-up of 28 months, 2-year locoregional control, distant control, progression-free survival, event-free survival and overall survival were 79, 83, 72, 63 and 80%, respectively. In 48 patients with available pre-treatment tissue, p16 overexpression was associated with significantly increased distant control (p=0.03), progression-free survival (p=0.02), event-free survival (p=0.007) and overall survival (p=0.03). The most common grade 3-4 toxicities were mucositis (46%), leukopenia (18%), anemia (18%) and dermatitis (17%). Concurrent 5-FU, HU, cetuximab and SIB-IMRT is a highly active regimen, particularly in patients with p16-positive disease.
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA. charles.tong@mssm.edu
Charles C L
CC
Tong
K H Vincent
KH
Lau
Michael
M
Rivera
David
D
Cannan
Julio
J
Aguirre-Ghiso
Andrew G
AG
Sikora
Vishal
V
Gupta
Kevin
K
Forsythe
Eric C
EC
Ko
Krzysztof
K
Misiukiewicz
Vivek
V
Gurudutt
Marita S
MS
Teng
Stuart H
SH
Packer
Eric M
EM
Genden
Johnny
J
Kao
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000068818:Cetuximab; D005472:Fluorouracil; D006918:Hydroxyurea