Phase II-trial of concomitant hyperfractionated-accelerated radiotherapy (HART) with cisplatin (Cis) plus cetuximab (Cet) for locoregionally advanced inoperable squamous cell head and neck cancer: 5-year end results

Background: Cet is a potent inhibitor of the epidermal growth factor receptor and has shown activity in squamous cell carcinoma of the head and neck (SCCHN) enhancing both radiotherapy and chemotherapy. We conducted a single arm phase II-trial to investigate the feasibility, efficacy and safety of combination therapy with Cis, Cet and HART. Methods: Patients ( pts) with stage III or IV, M0 SCCHN were enrolled and treated with an initial dosage of Cet (400mg/m2), followed by weekly dosage of 250mg/m2 during HART, which started with a prescribed dosage of 2.0 Gy per day for three weeks followed by 1.4 Gy twice daily to a total dosage of 70.6 Gy to the gross tumor volume. Cis 40 mg/m2 was administered weekly (d1,8,15,22,29,36). Results: From November 2007 through November 2010, 74 pts were enrolled, 65 pts (83% men) with a median age of 56 years (range 37 to 69 years) were evaluable. The median Karnofsky status, 90%; range, 50% to 100%; oropharynx primary tumor, 49% of patients; T4a,b, 65%; N2/3, 95%; stage IVA/B disease, 92%. Of theses were 85% smokers or ex-smokers. In the OPC patients neither p16 and HPV16 status was investigated. Of these 60 pts (92%) > 90% RT dosage, 49 pts (75%) > 90% Cet dosage and 56 pts (82%) > 4 cycles Cis 40 mg/m2 were applied. Complete remission rate (CR) was observed in 23/65 (35%). The most common grade >3 toxicity were mucositis (58%) and dysphagia (52%), grade >2 Cet related toxicity included dermatitis acneiform (15%) within the radiotherapy portals. With a median follow-up of 27 months; range 0 to 69 months; the 2- and 5-year overall survival rates are 64% and 41%, the 2-and 5- year progression-free survival rate are 45% and 32%, and the 2-year and 5-locoregional control rates are 47% and 33%. Conclusions: Combination therapy of SCCHN consisting of HART-Cis-Cet is an highly active regimen in this smoke - and alcohol-induced cancers. Further investigation is warranted to evaluate the efficacy of the trimodal approach in this very high risk patient Population.