Cetuximab (Erbitux^®) is an IgG1 epidermal growth factor receptor (EGFR)-targeting monoclonal antibody which has been shown in phase III trials to improve the survival of patients with squamous cell carcinoma of the head and neck (SCCHN) when combined with first-line platinum-based chemotherapy in recurrent and metastatic disease 1 and when combined with radiotherapy for the treatment of locoregionally advanced disease 23. In the phase III EXTREME trial in recurrent and metastatic SCCHN, first-line treatment with a combination of platinum (cisplatin or carboplatin), 5-fluorouracil (5-FU) and cetuximab not only significantly prolonged progression-free and overall survival, compared with platinum-based chemotherapy alone, but also increased the overall tumour response rate by 16 percentage points (36% with cetuximab/platinum/5-FU vs 20% with platinum/5-FU alone) 1. The tolerability of the two regimens was similar, with a few exceptions. As anticipated, grade 3/4 skin reactions and infusion-related reactions were confined to the cetuximab plus platinum-based chemotherapy arm of the trial. In addition, there were significantly more cases of grade 3/4 sepsis and hypomagnesaemia in the cetuximab/platinum/5-FU arm, compared with platinum-based chemotherapy alone, although the absolute numbers of patients were small. The effect of treatment on tumour response in this trial suggests that the combination of cetuximab and platinum-based chemotherapy may be particularly useful for symptomatic relief. We present here the case report of a patient with recurrent squamous cell carcinoma of the gum who derived rapid palliation of symptoms following treatment with a combination of cetuximab, carboplatin and 5-FU.

More than 50% of newly diagnosed patients with head and neck cancer are not cured with standard treatment approaches and will suffer local (more than 80%) and/or distant (less than 15%) relapse despite appropriate, aggressive therapy 4. For selected patients with a single, non-bulky recurrence, salvage surgery can be considered, although this is likely to result in some degree of functional deficit. An alternative option is re-irradiation, with or without concurrent chemotherapy, which may be beneficial in terms of locoregional control and survival, but which is associated with substantial toxicity. Indeed, in general, the use of re-irradiation should be limited to the setting of a clinical trial 5. When local treatment is not an appropriate option, single-agent or combination chemotherapy, is the standard treatment choice for good performance status patients. For the majority of patients with a poor performance status (Eastern Cooperative Oncology Group [ECOG] 2 or worse, equivalent to Karnofsky performance status 60% or less 6), like the patient discussed here, the only real option is best supportive care.

In patients receiving chemotherapy, the most commonly used schedule is one based on cisplatin combinations. For many years investigators have attempted to identify the gold standard first-line treatment, and randomised trials have compared the effects of cisplatin-based chemotherapy with other standard approaches or other cisplatin-based combinations 78. In terms of response rate, combination chemotherapy was superior to monotherapy, but did not improve survival. In addition, cisplatin-based combination chemotherapy was associated with more toxicity than monotherapy. Thus, for 30 years, in recurrent head and neck cancer, no first-line combination chemotherapy regimen had demonstrated a survival advantage over platinum-based chemotherapy. Therefore, the best option for these patients was to be treated within the context of a clinical trial utilizing therapy containing molecules against new targets, such as cetuximab, which was used in combination with a platinum agent and 5-FU in the EXTREME trial 1.

In our case report, adding cetuximab to carboplatin/5-FU led to a rapid reduction in the size of the facial mass, in facial oedema and in pain. Within 7 days of treatment, the patient's pain had reduced from 9/10 on a visual scale to 2/10 and after 3 cycles of treatment, pain was controlled without pain relief. Within 2 cycles of treatment, the facial mass had reduced to less than half its size prior to treatment initiation. The patient also reported an improvement in the ability to chew food. In addition, it was possible to administer cetuximab continuously as monotherapy for 7 months, during which time symptoms remained alleviated. It was eventually interrupted due to grade 2 mucositis and skin reactions. It is notable that facial pain returned on cetuximab cessation and decreased again following cetuximab resumption.

The response to the regimen of cetuximab and carboplatin/5-FU is particularly encouraging in view of the fact that it was achieved in a tumor that had less than six months earlier been irradiated and that had previously progressed rapidly on a combination of cisplatin and radiotherapy.

An association between platinum/5-FU chemotherapy, tumour response and symptom control in patients with recurrent and/or metastatic SCCHN was reported over ten years ago by Constenla et al.9. They reported that patients achieving an objective tumour response to treatment were more likely to obtain some symptom relief and improve their performance status than those not achieving a response. The phase III EXTREME trial showed that adding cetuximab to platinum-based chemotherapy significantly improved response rate compared with platinum-based chemotherapy alone 1. A quality of life analysis of this trial reported that adding cetuximab to platinum/5-FU did not adversely affect global quality of life 10. There were also some improvements with cetuximab/platinum-based therapy compared with platinum-based therapy alone in a number of parameters, including pain and swallowing 10.

The results of our case report are significant in that they demonstrate the speed with which symptom relief, associated with tumour mass reduction, can be achieved with cetuximab/carboplatin/5-FU for a patient with recurrent and/or metastatic SCCHN whose quality of life is severely compromised by their disease.

Written informed consent was obtained from the patient for the publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

RM has received reimbursement from Merck KGaA for participation in advisory boards and conferences. All other authors declare that they have no competing interests.

RM has participated in the conception and design the manuscript, manuscript writing and provided the clinical case. RP has participated in the manuscript design and provided the clinical case. MC has participated in elaborating the CT scan figures and text. EV has participated in providing the clinical case and manuscript writting. SV has participated in the conception and design the manuscript and manuscript writing. Final approval of manuscript: Ricard Mesía, Ramon Palmero, Mònica Cos, Esther Vilajosana and Silvia Vázquez.