Cetuximab Improves Outcomes of Head and Neck Cancers

NEW YORK FEB 09, 2006 (Reuters Health) - Treating patients with locoregionally advanced squamous-cell carcinoma of the head and neck with cetuximab plus radiotherapy improves survival over radiotherapy alone, without an increase in toxic effects, an international team of investigators reports.

Cetuximab (Erbitux, ImClone Systems) is a monoclonal antibody against the epidermal growth factor receptor (EGFR). EGFR is abnormally activated in epithelial cancers, the investigators note, and blockade of EGFR signaling sensitizes cells to the effects of radiation.

Dr. James A. Bonner, from the University of Alabama at Birmingham, and his colleagues conducted a phase 3 trial of patients with stage III or IV, nonmetastatic, squamous-cell carcinoma of the oropharynx, hypopharynx, or larynx.  They report their results in the New England Journal of Medicine for February 9.

A 7- to 8-week course of radiotherapy with curative intent was administered to patients in the radiotherapy only group (n = 213) and to the radiotherapy plus cetuximab group (n = 211).  Cetuximab was initiated 1 week before radiotherapy at a loading dose of 400 mg per square meter of body-surface area, followed by weekly 60-minute infusions of 250 mg per square meter for the duration of radiotherapy.

The median duration of locoregional control was 24.4 months in the combined therapy group and 14.9 months in the radiotherapy alone group (32% reduction in risk of locoregional progression, p = 0.005).

Corresponding overall median survival was 49.0 months versus 29.3 months (26% reduction in risk of death, p = 0.03).

Except for acneiform rash and infusion-related events, the incidence rates of severe reactions were similar in the two treatment groups, the authors report.

"Notably," they add, "cetuximab did not exacerbate the common toxic effects associated with radiotherapy of the head and neck, including mucositis, xerostomia, dysphagia, pain, weight loss, and performance-status deterioration."  Chemoradiotherapy, they note, is associated with high rates of severe and protracted mucositis.

They also suggest that efficacy of cetuximab plus radiotherapy compares favorably with the increases in efficacy associate with chemoradiotherapy.

While this regimen should be compared with other forms of chemoradiotherapy, Dr. Bonner and his colleagues note, "in the absence of these comparisons, physicians and patients should discuss the risks and benefits of each regimen on an individualized basis."

However, in a related editorial, Dr. Marshall R. Posner and Dr. Lori J. Wirth, from the Dana-Farber Cancer Institute in Boston, point out that chemoradiotherapy is the standard of care for locoregionally advanced squamous-cell carcinoma of the head and neck.

"Oncologists should keep in mind that all studies of platinum-based chemoradiotherapy have shown greater improvement in patients than Bonner et al. found with cetuximab," they note, and that phase 3 studies comparing the two regimens are warranted.

However, "Patients who cannot tolerate platinum-based chemotherapy for any of a variety of reasons should be expected to benefit from the addition of cetuximab to radiotherapy," Drs. Posner and Wirth indicate.

SOURCE:

• N Engl J Med 2006;354:567-578,634-635.