Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab

Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity.

We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck.

Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7 years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%).

Sixty-nine patients received at least 7 cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade ≥ 3 dermatitis; grade ≥ 2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade ≥ 3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56 days (47–75) compared to 51 days (47–65) in patients who did not require toxicity-related radiation interruptions (p < 0.05). After a median follow-up of 17.5 months (1.3–107.6) for all patients, median overall survival was 17.9 months (95% CI: 12.7–23.2), and loco-regional control (LRC) was 9.2 months (95% CI: 3.9–14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade ≥ 2 were independent prognostic factors for LRC (p = 0.023 and p = 0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p = 0.048 and 0.052, respectively).

Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.