Combination treatment using the monoclonal antibody cetuximab, along with high dose radiotherapy in the treatment of patients with loco-regionally advanced squamous cell carcinoma of the head and neck results in significant improvements in both loco-regional control and overall survival, according to Dr Jordi Giralt of Val d'Hebron University Hospital.
Head and neck cancers (e.g. oropharynx, hypopharynx and larynx) account for around 5% of all cancers and are responsible for around 200,000 deaths globally each year. The development of head and neck cancers is strongly linked to tobacco use. Squamous cell carcinoma accounts for nearly 95% of all head and neck cancers and the majority of these express the epidermal growth factor receptor (EGFR) that is associated with aggressive tumour growth and poor clinical outcome. Head and neck cancer is normally treated with high dose radiotherapy in combination with surgery.
These phase III results were based on data from 424 patients (recruited from April 1999 - March 2002) with a median follow-up of 38 months. Patients with loco-regionally advanced squamous cell carcinoma of the oropharynx, hypopharynx or larynx were randomised to receive either high-dose radiation alone for 6-7 weeks, or high-dose radiation plus weekly cetuximab. Cetuximab is a monoclonal antibody raised against EGFR. It is thought to work by binding to the EGFR so that epidermal growth factors cannot bind and stimulate the cells to grow. Pre-clinical studies have demonstrated radiosensitisation (enhancing the effect of radiation) with anti-EGFR treatments.
Median survival in the combined treatment arm was 54 months, versus 28 months in the radiotherapy alone arm. At 3 years post-treatment the overall survival benefit of the combined treatment was 57%, compared to 44% in the radiotherapy alone arm. Loco-regional control was also improved by cetuximab with radiotherapy: increasing from 59% - 69% at one year and from 48% - 56% at two years. “This is proof that drugs coming from the laboratory can be used to cure more patients”, said Dr Giralt.
Overall toxicity resulting from the combined treatment was dominated by recognised side effects of high dose head and neck irradiation e.g. mucositis (inflammation of the mucous membranes) and skin reactions. Treatment with cetuximab and radiotherapy in combination did raise the incidence of grade 3-4 skin reaction from 18% to 34% but the risk of grade 3-4 mucositis remained similar in both treatment arms. Cetuximab also carried a low (3%) risk of allergic reaction. “The substantial clinical benefit of this combination treatment can therefore be achieved with minimal enhancement of the toxicity we would expect to find associated with high dose radiotherapy alone”, explained Dr Giralt.
“These results are extremely promising and represent a major step forward in the treatment of squamous cell carcinoma of the head and neck,” said Dr Giralt. “This combination treatment should be explored in other common epithelial malignancies that demonstrate EGFR overexpression in which radiotherapy plays a central role.”