title: Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients.
abstract: OBJECTIVE
  Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment.
  
  
  METHODS
  Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction. In a phase III study, two daily amifostine doses, 200 mg/m(2) (n = 21) and 340 mg/m(2) (n = 18), were compared for protection against radiation induced toxicity. Total radiation dose was 60-70Gy (2Gy per fraction), nine patients received concurrent chemotherapy with cisplatin/5-FU. amifostine was usually discontinued after >1 episode of serious toxicity during subsequent treatment sessions.
  
  
  RESULTS
  In 16/39 patients (41%) amifostine was discontinued due to severe adverse effects, which led to discontinuation of the phase III study. In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1-3 days. Discontinuation occurred more often in patients receiving chemotherapy. The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients. Regarding our series and published series using an amifostine schedule comparable to ours, total discontinuation rate was 27% (57/214). Discontinuation was significantly influenced by chemotherapy (P = 0.007) but not by amifostine dose (P = 0.156).
  
  
  CONCLUSIONS
  Daily i.v. administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy.
authors.affiliation: Department of Radiation Oncology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, Hamburg D-20246, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Rades
authors.forename: Fabian
authors.initials: F
authors.lastname: Fehlauer
authors.forename: Amira
authors.initials: A
authors.lastname: Bajrovic
authors.forename: Birgit
authors.initials: B
authors.lastname: Mahlmann
authors.forename: Eckart
authors.initials: E
authors.lastname: Richter
authors.forename: Winfried
authors.initials: W
authors.lastname: Alberti
mesh_terms: D000328:Adult; D000368:Aged; D004999:Amifostine / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000528:radiation effects; D011832:Radiation Injuries / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000009:adverse effects*; D013280:Stomatitis / Q000517:prevention & control; D014839:Vomiting / Q000139:chemically induced; D014987:Xerostomia / Q000517:prevention & control
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine