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According to a study published in the Journal of Clinical Oncology, patients with head and neck cancers are more likely to benefit from accelerated radiation therapy if a high proportion of their cancer cells have receptors for epidermal growth factor, a growth factor that plays a role in cell proliferation and survival.

Among head and neck cancer patients receiving radiation therapy, one reason for treatment failure is the accelerated regrowth of cancer cells that can occur during fractionated radiation therapy (radiation therapy that is split into smaller doses and administered over the course of several days). To overcome this problem, researchers have investigated accelerated radiation therapy schedules. According to these schedules, higher daily doses of radiation are given over fewer days. Some patients may be more likely than others to benefit from these accelerated schedules. One factor that may influence patient response to different radiation therapy approaches is the presence of epidermal growth factor receptors (EGFR) on cancer cells. Epidermal growth factor plays a role in cell proliferation and survival, and cancer cells are more likely than normal cells to have receptors for this growth factor.

In order to determine whether patients with higher levels of EGFR are more likely to benefit from accelerated radiation schedules than patients with lower levels of EGFR, an international group of researchers assessed 304 head and neck cancer patients.

The researchers conclude that EGFR expression on cancer cells influences response to radiation therapy. Head and neck cancer patients with high EGFR levels appear to benefit from accelerated radiation therapy. Recent research has also evaluated the combination of radiation therapy with the EGFR-blocking drug Erbitux® (cetuximab) among patients with advanced head and neck cancer. These results are promising

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Researchers concluded that the addition of Erbitux to radiation therapy improves overall survival, progression-free survival and controls the spread of cancer more than radiation therapy alone in patients with advanced head and neck cancer. Patients with advanced head and neck cancer may wish to speak with their physician regarding their individual risks and benefits of participating in a clinical trial further evaluating Erbitux.

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According to results recently presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, the addition of Erbitux® (cetuximab) to radiation therapy improved survival by nearly 20 months compared to radiation therapy alone in the treatment of head and neck cancer.

A large phase III clinical trial (the MCL-9815 trial) was recently conducted to evaluate the effectiveness of Erbitux in head and neck cancers. Although preliminary results of this trial were previously released, results including specific survival times have recently been presented.

This trial included over 420 patients with head and neck cancer that had spread from the site of origin within the head and neck area, but not to distant sites in the body. Approximately half of the patients were treated with Erbitux plus radiation, while the other half was treated with radiation alone.

The researchers concluded that the addition of Erbitux to radiation therapy significantly improves survival and reduces the risk of a cancer recurrence compared to radiation therapy alone in patients with head and neck cancer.

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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.

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Recently, the following Head and Neck Cancers news articles have been published or updated:

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  Erbitux® Plus Chemotherapy and Radiation Therapy Promising in Head and Neck Cancer (2nd March 2006)
  According to results recently published in the Journal of Clinical Oncology, the treatment combination consisting of Erbitux® (cetuximab) plus chemotherapy and radiation therapy provides promising outcomes in the treatment of advanced head and neck cancer.
  
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  FDA Approves Erbitux® For Treatment of Head and Neck Cancer (2nd March 2006)
  The United States Food and Drug Administration (FDA) has approved the monoclonal antibody Erbitux® (cetuximab) for the treatment of head and neck cancer. The indication is for the use of Erbitux in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck, or as a single agent in recurrent or metastatic squamous cell carcinoma of the head and neck that has progressed following prior platinum-based chemotherapy.

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It’s the first significant treatment advance since the 1950s for a cancer that strikes some 29,000 Americans every year. The drug has been approved for use in combination with radiation in localized tumors or alone in metastatic disease.

Erbitux is one of the new targeted therapies in development against cancer. Unlike more conventional chemotherapy agents, which attack all rapidly reproducing cells, targeted therapies hone in on unique characteristics of cancer cells. As a result, the collateral damage to healthy tissue isn’t as great and side effects are greatly reduced.

“We consider this approval an important advance,” Dr. Steven Galson, the director of the Food and Drug Administration’s Center for Drug Evaluation and Research said in the FDA press release.

“When used with radiation, it (Erbitux) improves survival and reduces relapse without increasing side effects,” Dr. Ang said.

Unfortunately, not all tumors respond to Erbitux, as has been discovered in its use treating colon cancer. Dr. Ang said about 10-12% of patients will respond but he considers that a very good percentage. In addition, the physician will know within a couple of weeks whether the drug is eliciting a response.

Erbtiux is not without side effects. The most common are fever and chills, skin rash, fatigue/malaise, and nausea. Interestingly, the severity of the skin rash can be a good sign, showing that the drug is having eliciting a response.

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Researchers recently conducted a clinical trial to evaluate the effectiveness of Erbitux in combination with chemotherapy including Taxol® (paclitaxel) and Paraplatin as initial therapy in patients with head and neck cancers. This trial included patients who did not have metastatic cancer; some patients also received treatment with surgery and/or radiation therapy, depending on the aggressiveness and/or extent of spread of their cancer.

• 100% of patients achieved anticancer responses.
  
• 83% of patients achieved a complete disappearance of cancer (complete response).
  
• 17% of patients achieved a partial disappearance of cancer (partial response).
  
• Nearly one-quarter of patients were considered to be cancer-free following chemotherapy/Erbitux.
  
• Currently, three patients have experienced a recurrence of their cancer.
  Erbitux did not increase notable side effects; however, approximately half of patients treated with Erbitux experienced severe skin rash.
  
• Longer follow-up will provide progression-free and overall survival data for these patients.

The researchers concluded that the addition of Erbitux to standard chemotherapy appears highly active in the treatment of head and neck cancer. Longer follow-up will provide additional data regarding this treatment option.