ST. LOUISTo determine whether cytoprotective amifostine(Drug information on amifostine) (Ethyol) can reduce the incidence of hypothyroidism in patients with head and neck cancer treated with radiotherapy, a trial is set to begin at Washington University in St. Louis. The proposed trial is currently undergoing institutional review board (IRB) consideration and has not yet enrolled patients.
Describing the trial, Todd H. Wasserman, MD, noted that hypothyroidism can be measured in a variety of ways. "Biochemical changes as measured by thyroid stimulating hormone (TSH) or thyroxine (T4) can precede clinical changes by months to years. Prolonged stimulation by TSH is a significant risk factor in the development of thyroid cancer," Dr. Wasserman said. He is professor of radiation oncology, Department of Radiation Oncology, Washington University Medical Center.
"In a series of almost 1,800 Hodgkin’s disease patients, 44% of those irradiated to at least 30 Gy developed biochemical hypothyroidism within 25 years," Dr. Wasserman said. A similar study of 264 head and neck cancer patients in whom all or part of the thyroid had been irradiated with a median follow-up of 19 months found that 6% had clinical hypothyroidism and another 22% had biochemical hypothyroidism.
"Clinical data indicate that between 25% and 30% of head and neck cancer patients who receive neck radiation will become hypothyroid within a median of 18 months. Up to half of these patients will have clinical hypothyroidism," Dr. Wasserman said.
The proposed prospective nonrandomized phase II trial will use historical data as controls. Eligible patients will have head and neck cancers or lung cancer requiring radiotherapy that encompasses the thyroid.
Radiotherapy will be via CT-based treatment planning so that three-dimensional dose-volume data for the thyroid gland can be generated. Amifostine will be given at 500 mg/m² SC 30 minutes prior to each daily radiation fraction. The 500 mg of amifostine will be diluted in 2.5 mL of normal saline and injected in two 1.25-mL volumes into two sites of the anterior abdominal wall.
The researchers will measure thyroid function via TSH and total T4 before and at the end of treatment, and then in follow-up. Elevated TSH is defined as greater than 20 mU/mL or an elevated TSH as less than 20 mU/mL in conjunction with a decrease of total T4. Clinical hypothyroidism is defined as the presence of symptoms and/or signs in conjunction with biochemical hypothyroidism.
Surveillance for hypothyroidism will be via history, physical examination, and TSH/T4 measurement at 3, 6, 9, 12, and 24 months follow-up. Patients found to be hypothyroid will be treated with thyroid hormones. "We want to keep the TSH from staying elevated because of the risk of induction of thyroid cancer," Dr. Wasserman said.
Based on an expected 30% incidence of hypothyroidism at 1 year, the investigators plan to enroll 100 patients. Dr. Wasserman said that a 50% reduction in the incidence (to 15%) would be clinically significant.