Does Cytoprotection Play a Role in Lymphoma Pts Treated With Radiation to the Head and Neck?

BOSTON-Acute and longterm oral complications are welldocumented in lymphoma patients treated with irradiation, and older patients are particularly susceptible to xerostomia and dental problems. Andrea K. Ng, MD, MPH, a radiation oncologist at Brigham and Women's Hospital, Boston, and an assistant professor of radi- ation oncology at Harvard Medical School, is leading a randomized phase II trial to examine whether the cytoprotective agent amifostine(Drug information on amifostine) (Ethyol) will reduce radiation- related oral toxicities in lymphoma patients over 40 years of age who are treated with radiation to the head and neck. In discussing the rationale for this ongoing study, she noted that she and her Harvard colleagues are seeking additional collaborators. "We find that most younger patients recover salivary function within 1 to 2 months after radiation therapy, but when treating older patients we are faced with the question of either reducing or eliminating doses of radiation," she said. Quality-of-life measures are an important part of the study protocol. The investigators are measuring acute toxicities, especially of the skin, and late toxicities including those affecting the skin, subcutaneous tissues, mucous membranes, and salivary glands. Dr. Ng said that in the absence of cytoprotection, she would expect grade 2 or 3 xerostomia in about 60% of patients in this age group. Lymphoma Data Lacking
This study is needed, she emphasized, because data on amifostine as a radioprotector for oral complications are almost entirely from studies of patients with squamous cell carcinoma of the head and neck. "Compared with head and neck cancer patients, lymphoma patients tend to be younger at diagnosis, and they have longer lifeexpectancy, less history of tobacco or alcohol(Drug information on alcohol) use, better baseline oral health, and a history of exposure to different types of chemotherapy and different radiotherapy fields and doses," she said. "The longer life expectancy makes the question of long-term quality of life more important for these patients." The study is open to patients at least 40 years of age with histologically confirmed Hodgkin's or non- Hodgkin's lymphoma who as part of treatment will receive radiotherapy to the head and neck region, including Waldeyer's ring, the cervical and supraclavicular nodal chain, the parotid gland, or the full mantle field. Patients who have received prior radiation to the head or neck are excluded, as are stage I Hodgkin's patients receiving radiotherapy alone. Study Protocol
Patients are randomized either to amifostine (500 mg in 2.9 mL of normal saline, given SC 30 to 60 minutes before each radiation frac- fraction) or to radiation as planned without amifostine. "An observation arm is included because of the lack of published data formally documenting the rate of occurrence of mucositis and xerostomia in this patient population," Dr. Ng said. Toxicity will be assessed weekly during treatment and at 1, 3, 6, 12, 18, and 24 months post-treatment. Quality of life will be assessed by the EORTC [European Organization for Research and Treatment of Cancer]-QLQH& N and EORTC-QLQ-C30 instruments pretreatment and at 1, 3, 6, 12, 18, and 24 months posttreatment. Target accrual is 55 patients per arm, which will provide 83% power to detect a 33% reduction in grade 2 or worse xerostomia in the amifostine arm. Eight patients are currently on study, four on each arm. Citing an example of unanticipated issues that can complicate clinical research, Dr. Ng reported that six potentially eligible patients opted out of the study, three because of concern about a potential tumor-protective effect of amifostine. "This possibility was outlined in the consent form," she said. "We looked at the form again, and it now has been rephrased to say that no tumor-protective effects have been seen in other sites. The new language has just been approved by the IRB [Institutional Review Board]." Maria Werner-Wasik, MD, radiation oncologist and associate professor, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, said during the discussion period, "I commend the investigators for this study. It is going to be a major contribution to treatment. I've often wondered why we can't give amifostine to these patients."