title: A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck.
abstract: OBJECTIVE
  Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN.
  
  
  METHODS
  A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m(2) day 1; cisplatin, 75 mg/m(2) day 1; 5-fluorouracil [5-FU], 750 mg/m(2) day 1-5) and cetuximab, 250 mg/m(2) weekly (loading dose of 400 mg/m(2)). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF.
  
  
  RESULTS
  Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%).
  
  
  CONCLUSIONS
  C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.
authors.affiliation: Medical Oncology Department, Institut Català d'Oncologia L'Hospitalet, Barcelona, Spain. Electronic address: rmesia@iconcologia.net.
authors.forename: Ricard
authors.initials: R
authors.lastname: Mesía
authors.affiliation: Medical Oncology Department, Institut Català d'Oncologia L'Hospitalet, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vázquez
authors.affiliation: Medical Oncology Department, Hospital Clínic i Provincial, Barcelona, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Grau
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: García-Sáenz
authors.affiliation: Radiation Oncology Department, Institut Català d'Oncologia L'Hospitalet, Barcelona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Lozano
authors.affiliation: Medical Oncology Department, Hospital General Yagüe, Burgos, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: García
authors.affiliation: Medical Oncology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.affiliation: Medical Oncology Department, Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Irigoyen
authors.affiliation: Department of Otorhinolaryngology, Hospital de Bellvitge, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Mañós
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: García-Paredes
authors.affiliation: Medical Oncology Department, Gregorio Marañón University Hospital, Madrid, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: del Barco
authors.affiliation: Medical Oncology Department, Institut Català d'Oncologia L'Hospitalet, Barcelona, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Taberna
authors.affiliation: Medical Oncology Department, Gregorio Marañón University Hospital, Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Escobar
authors.affiliation: Medical Oncology Department, Hospital Clínico de Salamanca, Salamanca, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Cruz
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000068818:Cetuximab / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil