title: Induction chemotherapy and cetuximab for locally advanced squamous cell carcinoma of the head and neck: results from a phase II prospective trial.
abstract: PURPOSE To determine the potential efficacy of combining cetuximab with chemotherapy in patients with advanced nodal disease, we conducted a phase II trial with induction chemotherapy (ICT) consisting of six weekly cycles of paclitaxel 135 mg/m(2) and carboplatin (area under the curve = 2) with cetuximab 400 mg/m(2) in week 1 and then 250 mg/m(2) (PCC). PATIENTS AND METHODS Forty-seven previously untreated patients (41 with oropharynx primaries; 33 men, 14 women; median age, 53 years; performance status of 0 or 1) with squamous cell carcinoma of the head and neck (SCCHN; T1-4, N2b/c/3) were treated and evaluated for clinical and radiographic response. After ICT, patients underwent risk-based local therapy, which consisted of either radiation, concomitant chemoradiotherapy, or surgery, based on tumor stage and site at diagnosis. Results After induction PCC, nine patients (19%) achieved a complete response, and 36 patients (77%) achieved a partial response. The most common grade 3 or 4 toxicity was skin rash (45%), followed by neutropenia (21%) without fever. At a median follow-up time of 33 months, locoregional or systemic disease progression was observed in six patients. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 87% (95% CI, 78% to 97%) and 91% (95% CI, 84% to 99%), respectively. Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P = .012) and OS (P = .046). CONCLUSION ICT with weekly PCC followed by risk-based local therapy seems to be feasible, effective, and well tolerated. PFS is promising, and this sequential treatment strategy should be further investigated. Patients with HPV-positive tumors have an excellent prognosis.
authors.affiliation: Departments of Thoracic/Head and Neck Medical Oncology, Head and Neck Surgery, Radiation Oncology, Biostatistics, Radiology, and Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. mkies@mdanderson.org
authors.forename: Merrill S
authors.initials: MS
authors.lastname: Kies
authors.forename: Floyd Christopher
authors.initials: FC
authors.lastname: Holsinger
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: William N
authors.initials: WN
authors.lastname: William
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Glisson
authors.forename: Heather Y
authors.initials: HY
authors.lastname: Lin
authors.forename: Jan S
authors.initials: JS
authors.lastname: Lewin
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Ginsberg
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Gillaspy
authors.forename: Erminia
authors.initials: E
authors.lastname: Massarelli
authors.forename: Lauren
authors.initials: L
authors.lastname: Byers
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Waun K
authors.initials: WK
authors.lastname: Hong
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Adam S
authors.initials: AS
authors.lastname: Garden
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Papadimitrakopoulou
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D000068818:Cetuximab; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D027383:Papillomaviridae / Q000302:isolation & purification; D011446:Prospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D066246:ErbB Receptors; D017239:Paclitaxel; D000068818:Cetuximab