ALZA Corporation and MedImmune, Inc, recently announced the results of a phase III study evaluating the use of amifostine(Drug information on amifostine) (Ethyol) in the care of head and neck cancer patients who received radiation therapy. Recently published in the Journal of Clinical Oncology.(18:3339-3345, 2000), the report details the expanded use of amifostine in the reduction of moderate-to-severe xerostomia. Amifostine was approved by the US Food and Drug Administration in June 1999.
Reduces Incidence of Xerostomia
"The results of this study may be particularly useful to radiation oncologists in designing treatment approaches for the care of patients with head and neck cancer, a majority of whom will receive radiation treatment," said David Brizel, MD, associate professor of radiation oncology at Duke University Medical Center and one of the principal investigators in the study. "Ethyol has been demonstrated to help limit the degree of xerostomia that many patients may suffer as a result of head and neck cancer. In this study, the reduced incidence of xerostomia was evaluated according to accepted medical criteria as well as according to patients, who provided self-assessments of their symptoms."
Study Highlights Safety and Efficacy of Amifostine
The phase III, open-label, prospective, multicenter, randomized trial enrolled more than 300 patients with head and neck cancer. Results showed that approximately 1 month following treatment, 78% of patients given radiation alone experienced moderate-to-severe xerostomia, compared with 51% of patients who had been treated with amifostine prior to radiation. This represented a 35% reduction in incidence (P = .0001).
At 1 year following the completion of radiotherapy, 72% of the patients receiving amifostine could produce a clinically relevant volume of saliva (> 0.1 mL), compared with only 49% of those who did not receive amifostine. Moreover, 9 to 12 months after radiation therapy, 57% of patients in this trial who had been treated with radiation alone were still experiencing moderate-to-severe xerostomia, compared to 35% of patients in the amifostine arm.
In the study, patients evaluated their symptoms via the use of a questionnaire given during and after treatment. The questions addressed issues such as impairment of speech, taste, swallowing, need for oral comfort aids, and mouth dryness. Improvements in these subjective measurements of oral dryness were considered to support the efficacy of amifostine.
Treatment Side Effects
Side effects related to treatment with amifostine included nausea and vomiting (sometimes severe), hypotension, fever, allergic-type skin reactions, dizziness/lightheadedness, fatigue/lethargy, rigors/chills, sneezing, sleepiness/somnolence, and flushing. Of the 26 patients who discontinued amifostine due to side effects, all but one continued to receive radiation treatment.
Amifostine is indicated to reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation therapy for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands. It should not be administered in patients receiving definitive radiation therapy, except in the context of a clinical trial.