Manageable Early Toxicity of Cetuximab Concurrent with Radical Radiotherapy for Locally Advanced Head and Neck Cancer

Abstract

Sir d In 2006, Bonner et al. [1] compared radiotherapy with concurrent cetuximab (CtRT) with radiotherapy alone in the treatment of locally advanced head and neck squamous cell carcinoma (LAHNSCC). CtRT was associated with an improvement in overall survival of 20 months without any difference between groups in acute grade 3/4 in field toxicities or short-term quality of life. Matzinger et al. [2] published a detailed review of concurrent chemoradiotherapy, including the use of CtRT for LAHNSCC, in 2009. The National Institute for Health and Clinical Excellence (NICE) issued guidance on the use of CtRT for LAHNSCC in 2008 [3] for patients with an excellent Karnofsky performance status when platinum-based chemoradiotherapy is contraindicated. We have used CtRT in LAHNSCC from 2008 based on this guidance when there are contraindications to platinum treatment and/or when there is a perceived high risk of severe side-effects potentially leading to treatment interruptions. Such high-risk scenarios include re-irradiation with radical intent and large volume irradiation in the presence of advanced age with associated co-morbidities. In 2008, Lord et al. [4] reported a series of 14 patients receiving CtRT for LAHNSCC who had unexpectedly low rates of completing the cetuximab treatment due to treatment-related toxicities. Pryor et al. [5] reported similar results in a series of 13 patients in 2009. In 2010 we carried out a retrospective audit of cetuximab used in LAHNSCC on the basis of these reports. Twenty patients were treated with CtRT in our centre from 2008 to 2009. The median age was 63 years (range 39e84) and all were Karnofsky performance status score 80%. The primary sites were as follows: oral cavity (one; 5%), floor of mouth (one; 5%), oropharynx (10; 50%), larynx (five; 25%), hypopharynx (three; 15%) and maxillary antrum (one; 5%). Five patients (25%) had stage III disease and 15 (75%) were stage IV non-metastatic. A cetuximab 400 mg/m 2 loading dose was followed by 6 weekly cycles at 250 mg/m 2 . Radiotherapy was computed tomography planned with a three-dimensional conformal technique in eight patients (40%) and with intensity-modulated radiotherapy in 12 (60%). Seven patients received 72e66 Gy/36e33 fractions, 12 received 66 Gy/30 fractions and one patient 55 Gy/20 fractions. Grade 3 in-field skin toxicity was seen in five patients (25%) and grade 4 toxicity in two (10%). Grade 3 mucositis of the oropharynx and oesophagus occurred in 12 (60%) and nine (45%), respectively. No grade 4 mucosal toxicities were noted. Eighteen patients (90%) completed the planned number of cycles of cetuximab. Nineteen patients (95%) completed the radiotherapy course, 18 (90%) without interruption. Five patients (20%) were admitted to hospital for management of acute toxicities, four for mucosal and one for skin toxicity. Based on this experience, we believe CtRT to have acceptable toxicity rates compatible with high rates of completion of treatment that are comparable with those originally reported (Table 1).