Head and neck cancer medical therapy

General considerations
Improvements in diagnosis and local management, as well as targeted therapy, have led to improvements in quality of life and survival for head and neck cancer patients since 1992

After a histologic diagnosis has been established and tumor extent determined, the selection of appropriate treatment for a specific cancer depends on a complex array of variables, including tumor site, relative morbidity of various treatment options, patient performance and nutritional status, concomitant health problems, social and logistic factors, previous primary tumors, and patient preference. Treatment planning generally requires a multidisciplinary approach involving specialist surgeons and medical and radiation oncologists.

Several generalizations are useful in therapeutic decision making, but variations on these themes are numerous. Surgical resection and radiation therapy are the mainstays of treatment for most head and neck cancers and remain the standard of care in most cases. For small primary cancers without regional metastases (stage I or II), wide surgical excision alone or curative radiation therapy alone is used. More extensive primary tumors, or those with regional metastases (stage III or IV), planned combinations of pre- or postoperative radiation and complete surgical excision are generally used. Survival and recurrence risk has been roughly equivalent between surgical and radiation-based approaches, with a head-to-head comparison in only one randomized study. More recently, as historical survival and control rates are recognized as less than satisfactory, there has been an emphasis on the use of various induction or concomitant chemotherapy regimens.

Patients with head and neck cancer can be categorized into three clinical groups: those with localized disease, those with locally or regionally advanced disease, and those with recurrent and/or metastatic disease. Comorbidities (medical problems in addition to the diagnosed cancer) associated with tobacco and alcohol abuse can affect treatment outcome and the tolerability of aggressive treatment in a given patient.

Many different treatments and therapies are used in the treatment of throat cancer. The type of treatment and therapies used are largely determined by the location of the cancer in the throat area and also the extent to which the cancer has spread at time of diagnosis. Patients’ also have the right to decide whether or not they wish to consent to a particular treatment. For example, some may decide to not undergo radiation therapy which has serious side effects if it means they will be extending their lives by only a few months or so. Others may feel that the extra time is worth it and wish to pursue the treatments.

Radiation therapy
Radiation therapy is the most common form of treatment. There are different forms of radiation therapy. One of newer treatments is Intensity-modulated radiotherapy or IMRT which is able to focus more precisely so that fewer healthy cells are destroyed than was the case with some of the older radiation therapies. IMRT reduces incidental damage to the many important structures of the throat and mouth that may not be involved. However, if the cancer has metastisized or is widespread, the older form of treatment may be the most effective at slowing the progression of the disease. Radiation will generally cause the patient to feel sicker and weaker for several weeks following the treatment, but is a very effective treatment in stopping the disease.



Chemotherapy
Chemotherapy in throat cancer is not generally used to cure the cancer as such. Instead, it is used to provide an inhospitable environment for metastases so that they will not establish in other parts of the body. Typical chemotherapy agents are a combination of Taxol and Carboplatin. Erbitux is also used in the treatment of throat cancer. While not specifically a chemotherapy, Amifostine is often administered intravenously by a chemotherapy clinic prior to a patient's radiotherapy sessions. Amifostine protects the patient's gums and salivary glands from the effects of radiation.

Targeted therapy
Targeted therapy, according to the National Cancer Institute, is "a type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells without harming normal cells." Some targeted therapy used in squamous cell cancers of the head and neck include cetuximab, bevacizumab, and erlotinib.

The best quality data are available for cetuximab since the 2006 publication of a randomized clinical trial comparing radiation treatment plus cetuximab versus radiation treatment alone. This study found that concurrent cetuximab and radiotherapy improves survival and locoregional disease control compared to radiotherapy alone, without a substantial increase in side effects, as would be expected with the concurrent chemoradiotherapy, which is the current gold standard treatment for advanced head and neck cancer. Whilst this study is of pivotal significance, interpretation is difficult since cetuximab-radiotherapy was not directly compared to chemoradiotherapy. The results of ongoing studies to clarify the role of cetuximab in this disease are awaited with interest.

Another study evaluated the impact of adding cetuximab to conventional chemotherapy (cisplatin) versus cisplatin alone. This study found no improvement in survival or disease-free survival with the addition of cetuximab to the conventional chemotherapy.

However, another study which completed in March 2007 found that there was an improvement in survival.

The EXTREME (Erbitux in First-Line Treatment of Recurrent or Metastatic Head & Neck Cancer) study is a European multicenter phase III trial to determine whether adding cetuximab improves the impact of platinum-based chemotherapy.

Between December 2004 and March 2007, researchers enrolled 442 patients in 17 countries who had stage III or IV recurrent and/or metastatic SCCHN, and who were not candidates for further surgery or radiation. About half of the patients had cancer in their pharynx (throat), and a quarter in their larynx (voice box), but none in the nasopharynx (upper part of the throat). The patients averaged 57 years of age. Only about 10 percent were women.

Patients were randomly assigned to receive either chemotherapy (222 patients) or the same chemotherapy with cetuximab (220 patients). Chemotherapy consisted of 5-fluorouracil plus either carboplatin or cisplatin.

The trial was led by Jan Vermorken, M.D., Ph.D., of the University of Antwerp in Belgium. Vermmorken as well as other researchers involved in the trial have various relationships with Merck KGaA, Amgen, Oxygene, and sanofi-aventis. Merck KGaA provided funding for the study. (See the protocol summary.)

Results Patients treated with cetuximab reduced their risk of dying by 20 percent, surviving a median of 10.1 months compared to 7.4 months for those receiving chemotherapy alone.

Head and neck cancer clinical trials employing bevacizumab, an inhibitor of the angiogenesis receptor VEGF, are recruiting patients as of March, 2007. No published clinical trial information is available as of that date.

Erlotinib is an oral EGFR inhibitor, and was found in one Phase II clinical trial to retard disease progression. Scientific evidence for the effectiveness of erlotinib is otherwise lacking to this point. A clinical trial evaluating the use of erlotinib in metastatic head and neck cancer is recruiting patients as of March, 2007.