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Case presentation
The patient is a 75-year-old male who presented with a 4 week history of a sore throat and a left neck mass. He had a 60-pack per year history of smoking, a moderate history of alcohol intake and a history of depression, hypertension and diabetes. He lived alone, though he had family nearby. He was found to have a large left tonsil mass extending onto the soft palate and base of the tongue. There was an adjacent enlarged lymph node that was FDG avid on Positron Emission Tomography. With his advanced disease (stage IV), he would normally be a candidate for Cisplatin chemotherapy concurrent with radiotherapy. However, because of his age, medical problems and social condition, it was elected to treat him with Cetuximab (Erbitux, ImClone Systems) and Intensity Modulated Radiotherapy (IMRT) after placement of a feeding tube. After just 4 weeks of a planned 7-week course of treatment, his disease had completely resolved. He did have a severe enough skin reaction to cause a 2-week break in treatment, but he completed the rest of his care uneventfully.
Discussion
The treatment of advanced head and neck cancer has evolved over the years from a predominately surgery-based disease, to one that is treated primarily with radiotherapy. Advances in the prognosis of patients have been found with the addition of chemotherapy, altered fractionation schedules (i.e. twice daily) or a combination of the two. However, each of these advances has come at the price of increased short-term toxicity, especially in the elderly with co-morbid illnesses. This patient’s disease was advanced enough to warrant an aggressive approach that would be tolerable to him.
A recently reported randomized study (NEJM 2006;354:567-78) compared standard radiotherapy alone to standard radiotherapy with Cetuximab, an antibody against the binding region of the Epidermal Growth Factor Receptor (EGFR) which is abnormally activated in head and neck malignancies. In this trial, the median duration of local control of disease was 24 months with Cetuximab versus 15 months with radiotherapy alone. Median survival was also prolonged to 49 months compared to 30 months. The toxicity of treatment was no different between the two arms of the study except for some infusion reactions and an acneiform rash with the use of Cetuximab.
In this patient, it was felt that the addition of Cetuximab to IMRT would be tolerated well enough to warrant the potential of greater skin reaction with the combined treatment. It has been our experience that there has been greater oral cavity toxicity with the combined therapy that was not seen in the trial where the radiotherapy was delivered with opposed lateral fields (which was the convention at the time the trial was open). The use of IMRT technology in radiotherapy has improved local treatment control and lessened the long-term incidence of dry mouth by sparing the contralateral parotid and submandibular salivary glands from high doses of radiation (see accompanying figures 
). However, more of the oral cavity is exposed to modest doses of radiation. In our early experience with the use of Cetuximab, excessive lip radiation reactions were seen. We have since modified our planning approach to limit dose to the lips of patients with orpharyngeal cancer with gratifying results.
This patient has benefited from the advances in both radiation therapy and the biological treatment of malignancies found by testing newer treatment paradigms in cooperative clinical trials.
Email Dr. Bader. (Stephen.Bader@providence.org).