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.
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).
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%.
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.
Clinical trial identification
Legal entity responsible for the study
Merck Serono GmbH Darmstadt
All authors have declared no conflicts of interest.