Phase II evaluation of cetuximab (C225) combined with induction paclitaxel and carboplatin followed by C225, paclitaxel, carboplatin, and radiation for stage III/IV operable squamous cancer of the head and neck (ECOG E2303)

Reviewer: Christopher Dolinsky, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 2 de junio del 2007

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Presenter: H.J. Wanebo
Presenter's Affiliation: Landmark Medical Center, Woonsocket, RI
Type of Session: Scientific

Background

  • C225 (Cetuximab) is a monoclonal antibody directed against the epithelial growth factor receptor.
  • The combination of C225 and radiotherapy has been proven superior to radiation alone for the treatment of head and neck cancer, and the addition of C225 to radiation does not appear to increase the toxicity of radiation therapy.
  • Induction chemotherapy before combined chemoradiotherapy for locally advanced head and neck cancer has had mixed results; however, recent data suggests that this strategy may make sense in certain patients.
  • The addition of C225 to induction chemotherapy could potentially benefit certain patients with disease features that are predictive for poor outcomes following treatment.

Materials and Methods

  • A phase II study was undertaken to study the addition of C225 to induction chemotherapy with paclitaxel and carboplatin followed by concurrent C225, paclitaxel, carboplatin and radiation for patients with stage III/IV head and neck squamous cancers.
  • 74 patients were enrolled, and 67 were evaluable.
  • Primary and secondary endpoints included 1 year event free survival, pathologic complete response rates at the primary site, and toxicity.
  • Patients received induction C225, paclitaxel and carboplatin for 6 weeks and then had restaging biopsies performed at week 8 if they had a clinical response to treatment; patients with a positive biopsy went on to have radiotherapy to 50 Gy concurrent with C225, paclitaxel, and carboplatin.
  • If patients had an initially negative biopsy, they received full dose chemoradiotherapy to 68-72 Gy.
  • If patients had a positive biopsy after induction therapy, they then received another biopsy at 14 weeks (after the 50 Gy); if the biopsy was negative at that time, then they went on to receive completion chemoradiotherapy to 68-72 Gy.
  • If they had a persistent positive biopsy at 14 weeks, they were referred for salvage surgery.
  • Sites of disease included tonsil (30%), oral cavity/tongue (24%), base of tongue (42%), and larynx (34%).
  • 11% of patients were node negative.

Results

  • Of the 40 patients who received a biopsy at week eight, 26 (65%) of them had no residual tumor detected.
  • Restaging biopsy was done at week fourteen in 28 patients (14 who had an initially positive biopsy and 14 who had persistent gross tumor), and was negative in all 28 patients.
  • All 54 patients who had negative biopsies at some point were sent for completion chemoradiotherapy.
  • 44% of patients were able to receive the entire planned treatment.
  • The most common grade 3 or 4 toxicities included stomatitis (82%), dysphagia (29%), leukopenia (32%), and acneiform rash (12%).
  • There was one treatment related death.

Author's Conclusions

  • Neoadjuvant C225, paclitaxel and carboplatin followed by radiation concurrent with C225, paclitaxel, and carboplatin produced a complete pathologic response in 100% of patients who received at least 50 Gy.
  • This appears to be promising regimen and it deserves further study in a randomized setting.

Clinical/Scientific Implications

On the surface, this appears to be a "home run" considering that they are reporting that 100% of patients who got at least 50 Gy had a pathologic complete response to therapy. Although the follow-up is too short to get a sense of survival data, a complete response rate of 100% is quite impressive. However, we need to have a closer look at this trial. Why is it that only 44% of patients were able to receive the entire planned course of therapy? This number is very low and somewhat unsettling. The long term implications to this are unclear and need further follow up.  The standard of care for locally advanced head and neck cancer treatment involves concurrent chemoradiotherapy, and even though there are serious challenges in delivering an aggressive treatment to this body site, most centers can get a whole lot more than 44% of their patients through a planned course of chemoradiation. This trial is very interesting, and the authors should be commended for attempting this novel treatment approach. However, using C225 during induction therapy should only be considered in a trial setting.

Patient Summary: Phase II evaluation of cetuximab (C225) combined with induction paclitaxel and carboplatin followed by C225, paclitaxel, carboplatin, and radiation for stage III/IV operable squamous cancer of the head and neck (ECOG E2303)

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