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.

Molecular targeting in combination with platinum‐based chemoradiotherapy in head and neck cancer treatment

“…This skin toxicity was observed in a similar frequency as in the RTOG 0522 trial, although less often than in the trial of Bonner et al (87% of patients), which added cetuximab to RT. In terms of grade ≥3 mucositis, the rates were higher (45%, 54%, 59%, and 65%) than described in the group receiving CRT alone in RTOG 0522 (35%). In conclusion, the addition of cetuximab is associated with a higher rate of early and reversible side effects, such as mucositis and skin rash.…”

“…Data on survival and disease control stemming from this study are not yet available. Two other European studies showed response rates of 77% and 91% with cetuximab, but with lower OS rates (64% and 40%) than observed in the U.S. studies by Pfister et al (76%) and Ang et al (80%).…”

“…One of these studies was ended early after 2 treatment‐related deaths, which were considered to be severe adverse events . The other studies reported no treatment‐related deaths, but did describe, as expected, high rates of skin rash (15%, 18%, 28%, and 57%). This skin toxicity was observed in a similar frequency as in the RTOG 0522 trial, although less often than in the trial of Bonner et al (87% of patients), which added cetuximab to RT.…”

“…This could be due to the fact that the U.S. studies included a higher proportion of patients with oropharyngeal squamous cell carcinomas (SCCs; 60% and 70%) and fewer hypopharyngeal SCC tumors (hypopharyngeal SCC = 5% and 7%) compared with the European studies by Merlano et al (oropharyngeal SCC = 30%; hypopharyngeal SCC = 28%) and Kuhnt et al (oropharyngeal SCC = 49%; hypopharyngeal SCC = 30%). Compared with Europe, a higher percentage of oropharyngeal SCC in North America are induced by human papillomavirus (HPV) infection and show better survival when treated with radiation +/‐ chemotherapy in contrast to patients with tobacco‐related or alcohol‐related cancer .…”

“…A total of 4 phase II trials have previously investigated the effects of cetuximab together with platinum‐based CRT on treatment response, survival, and toxicity in single‐armed settings . One of these studies was ended early after 2 treatment‐related deaths, which were considered to be severe adverse events .…”