A phase II study to assess the efficacy of amifostine for submandibular/sublingual salivary sparing during the treatment of head and neck cancer with intensity modulated radiation therapy for parotid salivary sparing.

Intensity modulated radiation therapy (IMRT) allows for relative parotid salivary gland sparing for patients undergoing treatment for head and neck squamous cell cancer, but is less reliable for sparing the submandibular glands. Cytoprotection with amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) has been shown to decrease rates of acute and late xerostomia in patients undergoing radiation therapy for head and neck squamous cell cancer. The addition of amifostine to IMRT may augment parotid salivary sparing, and add submandibular/sublingual, and minor salivary gland sparing resulting in greater salivary flow rates and a more physiologic saliva. Eligible patients include those slated to receive definitive IMRT for early oropharynx cancer or postoperative RT, both without chemotherapy, for more advanced cancers. These include T1, T2 and favorable T3 (favorable, exophytic), N0-2b (small volume) M0 oropharynx cancers who are to receive bilateral neck RT. Postoperative patients with nodal metastases, T3 and T4 primaries, perineural invasion, and lymphovascular invasion will be eligible. Patients will receive 30 to 33 fractions. Clinical target volume (CTV) 1 will receive 60 to 66 Gy, CTV2 will receive 60 Gy, and CTV3 will receive 54 to 57 Gy. The mean dose goal for the parotid gland is 25 Gy. Patients will receive fixed-dose amifostine 500 mg subcutaneously 30 to 60 minutes before each radiation fraction. Subjective xerostomia questionnaires will be administered. Whole mouth and individual major salivary gland stimulated and unstimulated saliva will be collected before and after therapy at 6 weeks, 6 and 12 months. Xerostomia outcomes will be correlated with salivary dose volume histogram data. Accrual has not yet begun. The results of this study will give an indication of the objective and subjective benefit of combined IMRT physical parotid salivary sparing and amifostine chemical cytoprotection for combined salivary gland sparing and reduction in the rate of xerostomia in patients undergoing IMRT for head and neck squamous cell cancer.