Phase II trial of concomitant hyperfractionated-accelerated radiotherapy (HART) with cisplatin (Cis) plus cetuximab (Cet) for locoregionally advanced inoperable squamous cell carcinoma of the head and neck (LA SCCHN): Feasibility and 2-year OS.

Abstract

6077 Background: To report the mature data of a prospective phase II-trial to investigate the feasibility, efficacy and safety of combination therapy with Cis, Cet and HART in LA SCCHN. Methods: Patients (pts) with stage III or IV, M0 SCCHN were enrolled and treated with an initial dose of Cet (400 mg/m2), followed by weekly dose of 250 mg/m² before 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 for 6 weeks. Results: From February 2007 through November 2010, 74 pts were enrolled, 68 pts with a median age of 56 years (range 37 to 69 years) were evaluable. 50% had oropharyngeal SCC. Of these, 65 pts (96%) received > 90% RT dosage, 50 pts (74%) > 90% Cet dosage and 56 pts (82%) > 4 cycles Cis 40 mg/m². 3D-CRT was used in 72% and 28 patients are currently still being followed up. The most common grade >3 toxicities were mucositis (59%) and dysphagia (52%). Cet-related grade >2- toxicities included dermatitis (15%) within the radiotherapy portals. Nine (14%) pts were missing for response evaluation (e.g. withdrawal of consent). Complete remission rate [(p)CR] was observed in 23/68 (34%) including with 16 pts (24%) who reached a CR of the primary tumor but a selective lymph node dissection was performed 6-8 weeks after end of radiation treatment for residual neck disease. Furthermore, partial remission (PR) was achieved in 29/68 (43%), so an overall response (OR) of 52/68 (77%) was reached. No change/stable disease occurred in 3/68 pts (4%), progressive disease (PD) occurred in 1 pt (1%) and 3 pts (4%) have died due to disease progression. The 2-year overall survival and disease-free survival were 64.2% and 45.3%, respectively. Conclusions: Combination therapy of LA SCCHN consisting of HART-Cis-Cet is an highly active regimen. The addition of Cet to weekly Cis and daily RT was well tolerated and resulted in encouraging local disease control and survival rates. Clinical trial information: 2005-000355-15.