n ORLANDOAmifostine (Ethyol) given prior to radiation therapy in head and neck cancer patients significantly reduced the incidence of radiation-induced grade 2 xerostomia. Mucositis was not a dose-limiting toxicity, and patients generally were able to receive their scheduled radiation doses without delays,
David Brizel, MD, said at the American Society for Therapeutic Radiation and Oncology (ASTRO) meeting.
Xerostomia leads to secondary problems for patients, including difficulty in eating and speaking, and an increase in dental caries, loss of teeth, and oral infections, resulting in an overall pronounced decrease in quality of life, said Dr. Brizel, of the Department of Radiation Oncol-ogy, Duke University Medical Center.
Xerostomia can occur intermittently with standard fractionation schemes, he said, and can be permanent with cumulative doses exceeding 50 Gy.
This multinational randomized phase III trial took place from Oct 1995 to Aug 1997. The poster presented at the meeting showed the results of data available on the first 234 eligible patients who had a minimum of 3 months follow-up.
All patients had histologically confirmed squamous cell carcinoma of the head and neck, with 75% or more of the parotid gland included in the radiation treatment field.
Patients were stratified according to treatment center, site of disease (oropharynx, nasopharynx, oral cavity, larynx, other); nodal status (N0 vs N4); and total
radiation dose50 to 60 Gy for postoperative low-risk patients, 60 to 66 Gy for postoperative high-risk patients, and 66 to 70 Gy for those receiving definitive radiation therapy.
Arm I patients were given amifostine, 200 mg/m2 IV over 3 minutes, 15 to 30 minutes before each fraction (1.8 to 2.0 Gy/day for 30 to 35 fractions). Arm II patients received radiation therapy without pretreatment amifostine.
Stimulated and unstimulated saliva samplings were taken at baseline and at 1, 5, 11, 17, and 23 months post-radiation therapy. Xerostomia was rated according to the RTOG Acute Morbidity Criteria on a scale of 0 to 4, with 0 being no change from baseline and 4 being acute salivary gland necrosis.
Patients self-assessed symptoms on a 10-point analog scale looking at dryness of mouth, difficulty in speaking or eating, the need for fluids and oral comfort aids, and soreness of mouth. On this scale, 0 represents the most severe symptoms and 10 is absence of symptoms.
At 3 months after radiation therapy, patients in the amifostine arm showed significant benefit in terms of lessened symptoms, Dr. Brizel said. The amifostine patients had a median score of 7 for dry mouth, difficulty speaking, and need for fluids and oral comfort aids, compared with a median score of 5 for those on radiation therapy alone for dry mouth and difficulty speaking, and 4.5 for the need for fluids and oral comfort aids.
At 6-month follow-up, there was no difference in locoregional tumor control between the two groups, suggesting that amifostine did not adversely affect treatment efficacy.
The low daily dose of amifostine was generally well tolerated. Only eight patients in the amifostine group discontinued treatmentthree because of nausea and vomiting, one due to an allergic reaction, one with intercurrent illness, and three due to personal decision or noncompliance with the program. No new or cumulative toxicities were noted.
Dr. Brizel and his colleagues are currently doing a follow-up study to determine if pretreatment with amifostine reduces the incidence of late xerostomia in this setting. A further ongoing study is looking at the benefit of amifostine in patients receiving concurrent radioche-motherapy for head and neck cancer.