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.
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.
Wirth
L J
LJ
Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital. Electronic address: lwirth@partners.org.
Allen
A M
AM
Departments of Radiation Oncology.
Posner
M R
MR
Departments of Medical Oncology.
Haddad
R I
RI
Departments of Medical Oncology.
Li
Y
Y
Departments of Biostatistics and Computational Biology, Dana-Farber Cancer Institute.
Clark
J R
JR
Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital.
Busse
P M
PM
Department of Radiation Oncology, Massachusetts General Hospital.
Chan
A W
AW
Department of Radiation Oncology, Massachusetts General Hospital.
Goguen
L A
LA
Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Norris
C M
CM
Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Annino
D J
DJ
Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Tishler
R B
RB
Departments of Radiation Oncology.
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
D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D016190:Carboplatin; D017239:Paclitaxel