Annals of Oncology Advance Access published online on November 5, 2009
Annals of Oncology, doi:10.1093/annonc/mdp477
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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
1 Division of Hematology–Oncology, Department of Medicine, Massachusetts General Hospital
2 Department of Radiation Oncology
3 Department of Medical Oncology
4 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute
5 Department of Radiation Oncology, Massachusetts General Hospital
6 Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA
* Correspondence to: Dr L. J. Wirth, Division of Hematology–Oncology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Yawkey 7B, Boston, MA 02114 USA. Tel: +1-617-724-4000; Fax: +1-617-643-1915; E-mail: lwirth{at}partners.org
Background: Panitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN).
Patients and 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/m2 (n = 3) and 30 mg/m2 (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.
chemoradiotherapy, locoregionally advanced head and neck cancer, panitumumab
These authors contributed equally to this work. Received for publication January 20, 2009. Revision received August 28, 2009. Accepted for publication August 31, 2009.