Trial Information

Pilot Study to Evaluate Esomeprazole (Nexium) in Treating Gastro-Esophageal Reflux in Patients With Head and Neck Cancer With Prior External Beam Radiation Therapy: a Randomized, Prospective, Placebo-Controlled, Double-Blind Study.

The annual incidence of squamous cell carcinoma of the head and neck (SCCHN) is 40,000 cases
per year in the US and 60,000 cases per year in Europe. Radiation therapy is employed in
combination with chemotherapy in primary treatment or as adjuvant therapy for over half of
patients with SSCHN.

A high incidence of pathologic laryngopharyngeal reflux and gastroesophageal reflux is
observed in patients with head and neck cancer. When treatment for the cancer includes
radiation therapy, an incidence of 90% has been reported [2]. Although the interplay between
acid reflux and the development of head and neck cancer remains unclear, there is a strong
argument that radiation therapy worsens the problem by muting the body's ability to
neutralize acid.

Radiation therapy is extensively used in the treatment of squamous cell carcinoma of the
head and neck. Radiation therapy works by exploiting a survival differential between
malignant cells and normal cells. Simply stated, the malignant cells are more likely to die
with radiation when compared to normal non-malignant cells. However, not all normal cells
respond equally and some normal tissues have marked sensitivity to radiation damage.
Salivary glands are one such radiosensitive tissue that is permanently destroyed with
external-beam radiotherapy.

Damage to salivary tissues by radiation decreases their ability to excrete saliva. This is
supported by Olmos et al, who used salivary scintigraphy on both irradiated and
non-irradiated patients and found that 84% of those irradiated had total or partial
disturbance in both baseline and stimulated function. Of those treated with greater than
4500cGy, salivary excretion was almost invariably impaired. Xerostomia is the term for the
dry mouth, which can result from this loss.

In addition to the volume of the saliva, the contents of the saliva are also important. Helm
et al. "…evaluated the properties of human saliva relevant to its potential contribution to
esophageal acid clearance." By measuring the capacity for acid neutralization and plotting
titration curves, they identified that saliva and especially its bicarbonate content play an
important role in neutralization of esophageal acid in both resting and lozenge-stimulated
states.

As saliva plays an active role in the neutralization of esophageal acid and its clearance
from the esophagus, loss of saliva is predicted to increase the severity and incidence of
reflux as the protective effect of saliva's ability to clear and neutralize acid reflux is
diminished. Korsten et al., assessed the effects of chronic xerostomia on parameters of
gastroesophageal reflux and esophagitis and reported markedly impaired clearance of acid
from the esophagus and abnormal 24-hour intra-esophageal pH studies from a cohort of male
patients with xerostomia.

Medications are available to increase salivary flow but these are often minimally effective
and poorly tolerated. Decreasing stomach acid production is an alternative method of
mitigating the effect of GERD in these patients.

Esomeprazole has been proven beneficial in the treatment of gastroesophageal reflux disease
and is anticipated to be beneficial in treating SCCHN patients treated with external-beam
radiation therapy.