title: Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck.
abstract: BACKGROUND
  Panitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  This phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III-IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT.
  
  
  RESULTS
  Nineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m(2) (n = 3) and 30 mg/m(2) (n = 16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free.
  
  
  CONCLUSIONS
  Panitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital. Electronic address: lwirth@partners.org.
authors.forename: L J
authors.initials: LJ
authors.lastname: Wirth
authors.affiliation: Departments of Radiation Oncology.
authors.forename: A M
authors.initials: AM
authors.lastname: Allen
authors.affiliation: Departments of Medical Oncology.
authors.forename: M R
authors.initials: MR
authors.lastname: Posner
authors.affiliation: Departments of Medical Oncology.
authors.forename: R I
authors.initials: RI
authors.lastname: Haddad
authors.affiliation: Departments of Biostatistics and Computational Biology, Dana-Farber Cancer Institute.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital.
authors.forename: J R
authors.initials: JR
authors.lastname: Clark
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital.
authors.forename: P M
authors.initials: PM
authors.lastname: Busse
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital.
authors.forename: A W
authors.initials: AW
authors.lastname: Chan
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Goguen
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Norris
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Annino
authors.affiliation: Departments of Radiation Oncology.
authors.forename: R B
authors.initials: RB
authors.lastname: Tishler
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D000077544:Panitumumab; D010349:Patient Compliance; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D016190:Carboplatin; D017239:Paclitaxel