Phase II Randomized Trial of Surgery Followed by Chemoradiation Plus Cetuximab for High-Risk Squamous Cell Carcinoma of the Head and Neck (RTOG 0234)

Reviewer: Eric Shinohara MD, MSCI
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 29, 2007

Presenter: Paul Harari, MD
Presenter's Affiliation: University of Wisconsin
Type of Session: Scientific


  • Prior studies have demonstrated an improvement in local control and overall survival in post operative, high risk patients with locally advanced squamous cell carcinoma of the head and neck treated with concurrent chemotherapy and radiation (EORTC and RTOG).
  • In the definitive setting, concurrent cetuximab with radiation has been shown to improve local control and overall survival (N Engl J Med. 2006 Feb 9;354(6):567-78.). 
  • The combination of cetuximab with chemotherapy appears to be effective in the treatment of metastatic head and neck cancer (J Clin Oncol. 2006 Jun 20;24(18):2866-72).
  • The present abstract reports the safety and feasibility of concurrent chemoradiation with cetuximab in the postoperative setting.

Materials and Methods

  • The present study is a Phase II randomized trail of patients with locally advanced squamous cell carcinomas of the head and neck.  A total of 238 patients were accrued from April of 2004 to December of 2006.  At the time of the abstract presentation a total of 207 patients were analyzable.
  • All patients had stage III or IV squamous cell carcinoma of the head and neck.
    • The majority of patients had oral cavity or oral pharynx cancers.
    • Most patients in both groups had N2 disease and had stage IV (~94%).
    • All patients had high risk features.  These factors included microscopic positive margins, two or more positive neck nodes, or extracapsular extension (ECE).
    • ~50% of patients had ECE and ~84% of patients had greater than two positive lymph nodes.
  • All patients had a gross total resection.
  • 127 patients were treated with 3D conformal radiation using a shrinking field technique.  87 patients were treated with IMRT.  Patients were treated with 60-66 Gy to the tumor bed with elective nodes receiving 50 Gy.  Dose and technique were selected at the physician discretion.
  • All patients received cetuximab over 6 weeks and were randomized to receive either weekly cisplatin 30 mg/m2 or taxotere 15 mg/m2


  • There was increased hematologic toxicity in the cisplatin arm compared with the taxotere arm.
  • There was higher GI toxicity in the taxotere arm.
  • Grade 3 or 4 toxicity was seen in approximately 80% of patients in both arms.  Approximately 1/3 of patients had grade 3 or 4 mucositis in both groups.
  • Grade 4/5 toxicity was seen in 9.2% of patients in the cisplatin arm and 10.1% in the taxotere arm. 
  • Tolerability was defined as:
    • Completing 90% of radiation treatments
    • Completing 95% of cetuximab treatments
    • Completing 4 weeks of chemotherapy and cetuximab
    • In the cisplatin arm 75.5% of patients tolerated treatment.  In the taxotere arm 83.5% of patients tolerated treatment.
    • >90% of patients treated with IMRT tolerated combined treatment in both arms.
  • One patient in the cisplatin arm died of treatment related complications.

Author's Conclusions

  • Combined treatment with chemotherapy and cetuximab with concurrent radiation is safe and feasible, though highly toxic.
  • ~75% of patients tolerated treatment.
  • Efficacy data is to be available later with longer follow up.
  • Currently, the follow up is not long enough to determine if rates of feeding tube dependence are higher.
  • There will be a further analysis of toxicity in the IMRT versus 3D conformal groups which is to follow at a later date.

Clinical/Scientific Implications

  • Postoperative chemoradiation has been shown to be effective in reducing the risk of local recurrence and improve overall survival in high risk patients. However, local recurrence and mortality may be further improved on with the addition of biological agents.
  • These findings suggest that combined treatment with chemotherapy and cetuximab with concurrent radiation may be tolerable. However, it remains to be seen if there is greater efficacy warranting any possible increase in toxicity compared with concurrent chemotherapy and radiation.
  • Concurrent cetuximab with radiation improves local control in the definitive treatment of patients with locally advanced head and neck cancers. There has not been any large randomized studies demonstrating efficacy of cetuximab in the postoperative setting and this study is one of the first to address cetuximab’s use postoperatively.
  • Additionally, studies comparing cetuximab and cisplatin in the postoperative setting would further help our understanding of postoperative head and neck treatment. The most recent studies of chemotherapy with concurrent cetuximab in metastatic head and neck have been promising (EXTREME (Erbitux in First-Line Treatment of Recurrent or Metastatic Head & Neck Cancer). This suggests that the concurrent use of cetuximab with chemotherapy may have increased efficacy.

Partially funded by an unrestricted educational grant from Bristol-Myers Squibb.