Cytoprotective Effect on Post-IMRT Saliva Flow Studied in Head and Neck Cancer

ST. LOUIS-Xerostomia remains a devastating consequence of radiotherapy in head and neck cancer (HNC). An ongoing pilot study will examine whether treatment with the cytoprotectant amifostine(Drug information on amifostine) (Ethyol) can protect salivary flow in HNC patients who received amifostine prior to postoperative intensity-modulated radiation therapy (IMRT). Wade Larry Thorstad, MD, an instructor in radiation oncology at Washington University School of Medicine, St. Louis, reported that preliminary data show no decrease in either stimulated or unstimulated saliva flow at 6 months. Both variables will be compared against historical controls after 12 months of follow-up. The study enrolled 24 patients and is powered to detect a 30% or greater difference in salivary flow. Patients were treated with 500 mg of amifostine SC daily 15 to 60 minutes prior to each fraction of IMRT. Dr. Thorstad reported that 8 of 24 patients (33%) received all planned doses of amifostine and IMRT, 15 of 24 (63%) received 70% of the planned doses, and 19 of 24 (79%) received at least 60% of planned doses. Reasons for early stopping included nausea (9 of 24 patients [37%]), grade 3 rash (4 of 24 [17%]), fever and chills (2 of 24 [8%]), and pneumonia (1 of 24 [2%]). Two of 24 patients [8%] stopped radiotherapy because of mucositis or nausea. Nausea an Issue
When nausea emerged as an is- sue, the researchers looked more closely at the five of six initial patients who had complained of grade 2 or 3 nausea (four of whom had dropped out of the protocol early). Dr. Thorstad separated nausea into two components: nausea from thick secretions and pharyngeal wall mucositis related to radiation, and nausea related temporally to the amifostine injections. "Although IMRT is used to reduce long-term toxicity, it may produce increased acute toxicity," he pointed out. Among the nine patients who stopped treatment because of nausea, symptoms improved in five but were unchanged in four. Serotonin antagonists were added to the regimen, and only 4 of the next 18 patients discontinued treatment, Dr. Thorstad said. Longer Follow-up Needed
Fifteen patients have been enrolled in the trial, with followup of more than 6 months. Data were available and analyzed for 10 patients. "Historical data show that stimulated saliva flow decreases exponentially with radiation dose, by about 4% per Gray," Dr. Thorstad told Oncology News International. "Patients who have both parotids treated with more than 40 Gy have little residual salivary function without cytoprotection." Although preliminary data for 10 patients show little difference in salivary flow, Dr. Thorstad said more than half of these patients have had less than 6 months of follow-up, and there does appear to be substantial improvement in salivary flow in patients with at least 1 year of follow-up.