In this study, people with advanced head and neck cancer received either radiotherapy alone or radiotherapy together with a drug called cetuximab. Adding cetuximab kept the cancer in the head and neck area under control for longer and helped more people stay alive. Apart from an acne-like skin rash and reactions during the drug infusion, serious side effects were not very different between the two groups.
Locally advanced disease, only in cisplatin-ineligible patients
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Loading dose | |||
| Cetuximab | 400 mg/m² | IV, 120-minute infusion | One week before the start of radiotherapy |
| Subsequent doses | |||
| Cetuximab | 250 mg/m² | IV, 60-minute infusion | Weekly during radiotherapy, 1 hour before the radiation session |
| Radiotherapy | 6 to 7 weeks | External beam | Daily |
In HPV-positive oropharyngeal cancer, cetuximab resulted in lower survival than cisplatin and is not a substitute for it.
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
High-dose radiotherapy over 6 to 7 weeks in one of three schedules (chosen by the investigator before registration; a stratification factor): (1) once daily: 70.0 Gy in 35 fractions, 2.0 Gy per fraction, 5 fractions per week for 7 weeks; (2) twice daily (hyperfractionation): 72.0 to 76.8 Gy in 60 to 64 fractions, 1.2 Gy per fraction, 10 fractions per week for 6.0 to 6.5 weeks; (3) concomitant boost: 72.0 Gy in 42 fractions; first 32.4 Gy at 1.8 Gy per fraction, 5 fractions per week over 3.6 weeks, then two fractions a day over 2.4 weeks: morning 1.8 Gy (total 21.6 Gy) and afternoon 1.5 Gy (total 18.0 Gy), each 5 fractions per week. Across the trial, 56% received concomitant boost, 26% once-daily and 18% twice-daily radiotherapy. Patients with nodal disease greater than N1 at baseline underwent neck dissection 4 to 8 weeks after the end of radiotherapy (213 patients).
Cetuximab IV: initial dose 400 mg/m² over 120 minutes, one week before the start of radiotherapy; then 250 mg/m² over 60 minutes weekly during radiotherapy (6 to 7 weeks; 7 maintenance doses per the registered protocol), with the infusion completed at least 1 hour before the radiotherapy fraction. The protocol gave a 10-minute test dose before the loading dose. Premedication: an H1-receptor antagonist (FDA label). Radiotherapy as in the control group (211 patients).
Source of the regimen details: Radiotherapy dose and fractionation: Table 1 of Bonner et al. (2006) as quoted in the manufacturer's submission to NICE (technology appraisal TA145, 2006); cetuximab dose: FDA label for Erbitux (DailyMed, sections 2 and 14) and ClinicalTrials.gov NCT00004227
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients aged 18 years or older with previously untreated, measurable, locoregionally advanced squamous-cell carcinoma of the oropharynx, hypopharynx or larynx, stage III or IV without distant metastases; Karnofsky performance status 60 to 100; neutrophils 1500/µL or more, platelets 100,000/µL or more, creatinine no more than 1.5 mg/dL or creatinine clearance 50 mL/min or more. 60% oropharynx, 25% larynx and 15% hypopharynx; 90% with Karnofsky 80 or more (FDA label).
Primary endpoint: duration of locoregional disease control. Secondary endpoints: overall survival, progression-free survival, response rate and safety.
Apart from acneiform rash and infusion reactions, the incidence of grade 3 or higher adverse events, including mucositis, did not differ significantly between the two groups.
According to the FDA label (BONNER): acneiform rash 87% (grade 3–4: 17%) vs 10% (1%); infusion reactions 15% (grade 3–4: 3%) vs 2%; grade 3–4 radiation dermatitis 23% vs 18%; grade 3–4 weight loss 11% vs 7%. Cardiopulmonary arrest or sudden death occurred in 2% of 208 patients in the cetuximab group; monitoring of electrolytes (magnesium, potassium and calcium) during and after treatment is recommended.
This trial showed that adding cetuximab to high-dose radiotherapy in locoregionally advanced squamous-cell carcinoma of the head and neck improves locoregional control and overall survival without increasing the common toxic effects of radiotherapy. The place of this approach in current clinical guidelines and drug approvals should be checked separately; the abstract does not address them.
The abstract does not mention the study's limitations. Details of the inclusion criteria, radiotherapy dose and schedule, and subgroup analyses can be checked in the full paper.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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